Malabsorption Syndrome

The Gastrointestinal (GI) Tract amp Absorption

Malabsorption Syndrome

Maldigestion impaired breakdown of nutrients (carbohydrates protein fat) to absorbable split-products (mono- di- or oligosaccharides amino acids oligopeptides fatty acids monoglycerides)

Malabsorption defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements

Malabsorption Syndrome

Malabsorption Syndrome is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by the gastrointestinal tract

The digestion or absorption of a single nutrient component may be impaired as in lactose intolerance due to lactase deficiency

However when a diffusion disorder such as celiac disease or Crohns disease affects the intestine the absorption of almost all nutrients is impaired

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The Gastrointestinal (GI) Tract amp Absorption

Malabsorption Syndrome

Maldigestion impaired breakdown of nutrients (carbohydrates protein fat) to absorbable split-products (mono- di- or oligosaccharides amino acids oligopeptides fatty acids monoglycerides)

Malabsorption defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements

Malabsorption Syndrome

Malabsorption Syndrome is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by the gastrointestinal tract

The digestion or absorption of a single nutrient component may be impaired as in lactose intolerance due to lactase deficiency

However when a diffusion disorder such as celiac disease or Crohns disease affects the intestine the absorption of almost all nutrients is impaired

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Malabsorption Syndrome

Maldigestion impaired breakdown of nutrients (carbohydrates protein fat) to absorbable split-products (mono- di- or oligosaccharides amino acids oligopeptides fatty acids monoglycerides)

Malabsorption defective mucosal uptake and transport of adequately digested nutrients including vitamins and trace elements

Malabsorption Syndrome

Malabsorption Syndrome is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by the gastrointestinal tract

The digestion or absorption of a single nutrient component may be impaired as in lactose intolerance due to lactase deficiency

However when a diffusion disorder such as celiac disease or Crohns disease affects the intestine the absorption of almost all nutrients is impaired

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Malabsorption Syndrome

Malabsorption Syndrome is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by the gastrointestinal tract

The digestion or absorption of a single nutrient component may be impaired as in lactose intolerance due to lactase deficiency

However when a diffusion disorder such as celiac disease or Crohns disease affects the intestine the absorption of almost all nutrients is impaired

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The digestion or absorption of a single nutrient component may be impaired as in lactose intolerance due to lactase deficiency

However when a diffusion disorder such as celiac disease or Crohns disease affects the intestine the absorption of almost all nutrients is impaired

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology(Mechanism)

In general the digestion and absorption of food

materials can be divided into 3 major phases

Luminal Mucosal Post - absorptive

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The luminal phase is the phase in which dietary fats proteins and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile

The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

In the post - absorptive phase reassembled lipids and other key nutrients are transported via lymphatic and portal circulation from epithelial cells to other parts of the body

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Causes of Malabsorption Syndrome

The best way to classify the numerous causes of

malabsorption is to consider the 3 phases of

digestion and absorption

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The Luminal Phase Impaired nutrient hydrolysis

The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis pancreatic resection pancreatic cancer or cystic fibrosis The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption respectively

Inactivation of pancreatic enzymes by gastrichypersecretion as seen in Zollinger-Ellisonsyndrome is another cause

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The Luminal Phase Inadequate mixing of nutrients bile and

pancreatic enzymes as seen in rapid intestinal transit gastrojejunostomy total and partial gastrectomy or intestinal resection after mesenteric emboli or thrombosis also causes impaired hydrolysis

Rarely a failure to convert a proenzyme to active form such as enterokinase and trypsinogen deficiencies also can cause protein maldigestion and malabsorption

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Impaired micelle formation

Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption This impairment is due to different reasons including

(1) decreased bile salt synthesis from severe parenchymal liver disease (eg cirrhosis)

(2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg primary biliary cirrhosis primary sclerosing cholangitis)

(3) impaired enterohepatic bile circulation as seen in small bowel resection or regional enteritis or

(4) bile salt deconjugation due to small bowel bacterial overgrowth

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Stasis of intestinal content caused by a motor

abnormality (eg scleroderma diabetic neuropathy intestinal obstruction) an anatomic abnormality (eg small bowel syndrome stricture ischemia blind loops) or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Luminal availability and processing

Luminal bacterial overgrowth can cause a decrease in the availability of substrates including carbohydrates proteins and vitamins (eg vitamin B-12 folate)

Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Mucosal phase

Impaired brush-border hydrolase activity

Disaccharidase deficiency can lead to disaccharide malabsorption

Lactase deficiency either primary or secondary is the most common form of disaccharidase deficiency Genetic factors determine primary lactase deficiency Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection) chronic alcoholism celiac sprue radiation enteritis regional enteritis or AIDS enteropathy

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Mucosal phase

Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet

Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc leading to villous atrophy and acral dermatitis

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Mucosal phase

Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells Additional cell types affected by auto antibodies include islet and parietal cells

Other carbohydrase deficiencies such as sucrase-isomaltase deficiency may be the cause

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Mucosal phase

Impaired nutrient absorption

Nutrient malabsorption is due to inherited or acquired defects

Inherited defects include glucose-galactose malabsorption abetalipoproteinemia cystinuria and Hartnup disease

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Acquired disorders are far more common and are caused by the following

(1) decreased absorptive surface area as seen in intestinal resection of intestinal bypass

(2) damaged absorbing surface as seen in celiac sprue tropical sprue Crohns disease AIDS enteropathy chemotherapy or radiation therapy

(3) infiltrating disease of the intestinal wall such as lymphoma and amyloidosis and

(4) infections including bacterial overgrowth giardiasis Whipples disease cryptosporidiosis and microsporidiosis

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Post - absorptive Phase

Obstruction of the lymphatic system both congenital (eg intestinal lymphangiectasia Milroy disease) and acquired (eg Whipple disease neoplasm [including lymphoma] tuberculosis) impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

External Causes

Hyperthyroidism Hypothyroidism Addisons disease Diabetes mellitus Hyperparathyroidism Hypoparathyroidism Carcinoid syndrome Widespread skin disease Malnutrition Collagen diseases Eating disorders

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk Factors

Factors that may increase your chance of having

malabsorption include

Medical conditions affecting the intestine Use of laxatives Excessive use of antibiotics Intestinal surgery Excessive use of alcohol Travel to countries with high incidence of

intestinal parasites

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Symptoms of Malabsorption Syndrome

The osmotic load resulting from the

inability of the intestine to absorb certain nutrient elements causes the presenting symptoms On occasion the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Diarrhea

Diarrhea is the most common symptomatic complaint

Diarrhea frequently is watery reflecting the osmotic load received by the intestine

Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine further worsening the diarrhea

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Steatorrhea

Steatorrhea is the result of fat malabsorption

The hallmark of steatorrhea is the passage of pale bulky and malodorous stools

Such stools often float on top of the toilet water and are difficult to flush Also patients find floating oil droplets in the toilet following defecation

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Weight loss and fatigue

Weight loss is common and may be pronounced however patients may compensate by increasing their caloric consumption masking weight loss from malabsorption

The chance of weight loss increases in diffusion diseases involving the intestine such as celiac disease and Whipple disease

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Flatulence and abdominal distention

Bacterial fermentation of unabsorbed food substances releases gaseous products such as hydrogen and methane causing flatulence

Flatulence often causes uncomfortable abdominal distention and cramps

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Edema

Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema

Extensive obstruction of the lymphatic system as seen in intestinal lymphangiectasia can cause protein loss

With severe protein depletion ascites may develop

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Anemia

Depending on the cause anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency)

Iron deficiency anemia often is a manifestation of celiac disease

Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Bleeding disorders

Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia

Ecchymosis usually is the manifesting symptom although occasionally melena and hematuria occur

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Metabolic defects of bones

Vitamin D deficiency can cause bone disorders such as osteopenia or osteomalacia

Bone pain and pathologic fractures may be observed

Malabsorption of calcium can lead to secondary hyperparathyroidism

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Neurologic manifestations

Electrolyte disturbances such as hypocalcemia and hypomagnesemia can lead to tetany manifesting as the Trousseau sign and the Chvostek sign

Vitamin malabsorption can cause generalized motor weakness (pantothenic acid vitamin D) or peripheral neuropathy (thiamine) a sense of loss for vibration and position (cobalamin) night blindness (vitamin A) and seizures (biotin)

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Physical Signs of Malabsorption

General Manifestations

Patients may have orthostatic hypotension

Patients may complain of fatigue Signs of weight loss muscle wasting or

both may be present Patients may have signs of loss of

subcutaneous fat

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Abdominal manifestations

The abdomen may be distended and bowel sounds may be hyperactive

Ascites may be present in severe hypoproteinemia

Dermatologic manifestations

Pale skin may reveal anemia Ecchymoses due to vitamin K deficiency may be

present Dermatitis herpetiformis erythema nodosum

and pyoderma gangrenosum may be present Pellagra alopecia or seborrheic dermatitis may

be present

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Neurologic al manifestation

Motor weakness peripheral neuropathy or ataxia may be present

The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia

Cheilosis glossitis or aphthous ulcers of the mouth

Peripheral edema

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Possible Complications

Long-term malabsorption can result in

Anemia Gallstones Kidney stones Osteoporosis and bone disease Malnutrition and vitamin deficiencies

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Celiac Disease

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Celiac Disease

Celiac disease is a digestive disorder It is caused

by an immune reaction to gluten Celiac disease is

also known as

Celiac sprue Non - tropical sprue gluten intolerance gluten-sensitive enteropathy

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Celiac disease (CD) is an immune-mediated disorder theonly one with a well-established origin resulting from apermanent gluten intolerance which primarily involves thegastrointestinal tract

It is characterized by the presence of chronic inflammationof the small bowelrsquos mucosa and submucosa and is clinicallycharacterized by the presence of diverse systemic manifestations

It may start at any age both during childhood andadolescence and is also relatively common in adulthood

It is being increasingly diagnosed even in elderly patients (upto 20 of patients are older than 60 years at the time ofdiagnosis)

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The causative agent gluten is well established a mixtureof proteins present exclusively in cereals ndashmainlywheat barley rye and oats- but not corn

It affects only predisposed individuals whose most susceptible genetic features are related to human leukocytes antigens from class two (HLA-1056152) predominantly HLA-DQ2 (90) while much less frequency HLA-DQ8 (5-10)

However these genetic markers are a necessary but nota sufficient condition since a significant frequency ofCD patients (5-10) are DQ2 and DQ8-negative Thismeans that other still not well-established genotypesmay exist that probably correspond to the class one HLAsystem (HLA-1056152) including MICA MICB and others

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

A strong genetic susceptibility is present with about75 concordance rate among monozygotic twins

Certainpopulations have an increased prevalence of CD Forinstance the first-degree relatives of individuals withbiopsy-proven CD have a prevalence between 4-12 ofthose suffering from this disease

Second-degree relatives also appear to have an increased

prevalence Patients with type 1 diabetes mellitus (IDDM) have a prevalence of CD ranging to 3-8 In Downacutes syndrome the presence of CD is found between 5-12 Also CD is associated with Turnerrsquos and Williamrsquossyndromes IgA deficiency and several autoimmune disorders

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk Factors for Celiac Disease

People suffering from other immune diseases and certain geneticdisorders are more likely to have celiac disease Some disorders associated with celiac include

rheumatoid arthritis type 1 diabetes thyroid disease autoimmune liver disease Addisonrsquos disease Sjogrenrsquos disease lupus Down syndrome Turner syndrome lactose intolerance intestinal cancer intestinal lymphoma

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathogenesis The triggers for CD are specific immunogenic peptidesthat are present only and exclusively in the dietary glutenproteins from wheat and similar structural cereals such asrye and barley These peptides are resistant to digestion

bygastric and pancreatic enzymes and find their way into thelamina propria of the small bowel presumably after somechanges occur in the intercellular tight junctions with anincrease in the intestinal permeability

One such peptide is a 33-amino acid sequence which is

a potent activator of specific T-cell lines from patients with CD

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The subsequent infiltration by CD4 (+) TLymphocytes into the lamina propria and CD8 (+) into the intestinal epithelium are a hallmark of active CD

The recognition of HLA-bound gluten peptides by T cells leads to their activation and clonal

expansion of B cells that produce antibodies Other cytokines released by activated CD4 T cells that involve the adaptive immune response promote various inflammatory mechanisms and produce the intestinal lesion

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Less information is available on the activation and mode of action of intraepithelial T cells which are mediated by the innate immune system The expression of the interleukin-15 cytokine appears to play a central role in driving various processes that lead to the increased number of intraepithelial lymphocytes (IELs) as well as in the destruction process of the epithelial cells and the mucosal damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Tissue transglutaminase 2 (tTG) plays an importantrole in the immune response and is present in severaltissues in the body The cross-linking activity of tTGis involved in several functions such as wound healingformation of cell envelopes in apoptosis and Stabilization of the extra-cellular matrix In addition this enzyme can deaminate glutamine residues

Glutamine-rich gluten peptides are therefore excellent substrates for tTG The resulting deaminated and thus negatively-charged peptides have much higher affinity for the HLA-DQ2 and DQ8 molecules and have a key step in the immune response in CD

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Normal Pathology

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk groups and associated disorders

First degree relatives Downacutes and turneracutes syndromes IgA selective deficiency

Endocrine diseaseso Type 1 diabetes mellituso Autoimmune thyroid diseaseso Alopecia areata

Neurologic diseaseso Cerebellar ataxiao Epilepsyo Peripheral neuropathyo Multiple sclerosis

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Liver diseaseso Primary biliary cirrhosiso Autoimmune hepatitiso Autoimmune cholangitiso Idiopathic hypertransaminasemia

Rheumatologic diseaseso Rheumatoid arthritiso Sjoumlgrenacutes syndrome

Heart diseaseso Idiopathic dilated cardiomyopathyo Autoimmune myocarditis

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Cutaneous diseaseso Dermatitis herpetiformiso Psoriasiso Vitiligo

Otherso Iron-deficiency anemiao Osteoporosiso Increased risk of fractureso Infertilityo Amenorrheao Dental enamel defectso Depression and anxietyo Chronic asthenia

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Epidemiology

Until the last decade CD was considered to be a rare disease but today it is known to be universally distributed to involve all races and it is one of the most commonly known genetic diseases with a mean prevalence of 1-2 in the general population being clearly underestimated and under diagnosed worldwide

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Clinical Presentations

The clinical presentation of CD varies greatly rangingfrom asymptomatic to severely malnourished patients

The most common clinical manifestations of CD include abdominal cramping pain with moderate to severe abdominal distension frequently associated with relapsing or permanent dyspepsia presence of gastro-Esophageal reflux (GERD) and recurrent episodes of altered bowel habits (diarrhea andor constipation) weight loss bone disease anemia and weakness

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

While diarrhea was almost considered apersistent symptom this is not the case in

adultsand up to 50 of patients predominantly

haveconstipation which on many occasions

becomesrefractory to all types of therapy

It should be noted that up to 30 of celiac patients have increased body mass index

(BMI) and obvious obesity at diagnosis

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

CD is sometimes divided into clinical subtypes Theterms ldquosymptomatic or classicrdquo apply to cases that meetthe typical features described above

By contrast in the ldquoatypical formsrdquo of the disease the Gastrointestinal symptoms may be absent or less pronounced and in this case the extra-intestinal features predominate such as chronic iron deficiency anemia osteoporosis short stature or failure to thrive infertility

and increased number of abortions

Since atypical presentations are found more frequentlyin later decades CD is now considered to be amultisystemic disorder rather than a sole gastrointestinalprocess

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Gastrointestinal Symptoms

Diarrhea is the most common symptom in untreated celiac sprue and present in 45-85 of all patients Diarrhea caused by celiac sprue is due to maldigestion and malabsorption of nutrients The stools might be watery or semiformed light tan or gray and oily or frothy The stools have a characteristic foul odor In infants and young children extensive diarrhea can lead to severe dehydration electrolyte depletion and metabolic acidosis

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Gastrointestinal Symptoms

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel This results in the production of hydroxy fatty acids by bacteria which causes secretion of fluids into the intestine

Flatulence (28 of patients) and borborygmus (35-72 of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive or even explosive

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Gastrointestinal Symptoms Weight loss (present in 45 of all patients) is variable

because some patients might compensate for the malabsorption by increasing dietary intake In infants and young children with untreated celiac sprue failure to thrive and growth retardation are common

Weakness and fatigue (prevalence 78-80) are usually related to general poor nutrition In some patients severe anemia can contribute to fatigue Occasionally severe hypokalemia due to the loss of potassium in the stool can cause muscle weakness

Severe abdominal pain (prevalence 34-64) is unusual in

patients with uncomplicated celiac sprue However abdominal bloating or cramps with excessive malodorous flatus is a common complaint

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Extra - Intestinal Symptoms

Anemia (10-15 of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine In severe celiac disease with ileal involvement absorption of vitamin B-12 might be impaired

A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Extra - Intestinal Symptoms

Osteopenia and osteoporosis (prevalence 1-34) might cause bone pain for several reasons including defective calcium transport by the diseased small intestine vitamin D deficiency and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids

Neurologic symptoms (frequency 8-14) that result from hypocalcaemia include motor weakness paresthesias with sensory loss and ataxia Seizures might develop because of cerebral calcifications[3]

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Extra - Intestinal Symptoms

Skin disorders including dermatitis herpetiformis (a pruritic papulovesicular skin lesion involving the extensor surfaces of the extremities trunk buttocks scalp and neck) is associated in 10-20 of patients with celiac disease

Hormonal disorders such as amenorrhea delayed menarche and infertility in women and impotence and infertility in men have been described

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Physical

Abdominal examination shows a protuberant and tympanic abdomen due to distention of intestinal loops with fluids and gas Ascites occasionally can be detected in patients with severe hypoproteinemia

Evidence of weight loss including muscle wasting or loose skin folds

Orthostatic hypotension

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Physical

Peripheral edema

Ecchymoses

Hyperkeratosis or dermatitis herpetiformis

Cheilosis and glossitis

Evidence of peripheral neuropathy

Chvostek sign or Trousseau sign

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Associated conditions

Malignant disease

Malignant diseases are more frequent in patients with long-term untreated classical CD Small-bowel adenocarcinoma esophageal and oropharyngeal squamous-cell carcinoma and non-Hodgkinrsquos lymphoma occur more often in CD patients than in healthy control individuals

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Osteoporosis

Measurement of bone mineral density is recommended when CD has been diagnosed as reduced bone density is common in both adults and children with CD The reduction in bone density is more severe in symptomatic CD than in the silent form and is associated with an increased risk of fracture

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Autoimmune disorders

Autoimmune disorders occur ten times more frequently in adult patients with celiac disease than in the general population

Such disorders include bull Insulin-dependent type 1 diabetes bull Thyroid disease bull Sjoumlgrenrsquos syndrome bull Addisonrsquos disease bull Autoimmune liver disease bull Cardiomyopathy bull Neurological disorders

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Dermatitis herpetiformis

Dermatitis herpetiformis is considered to be a cutaneous manifestation of gluten sensitivity in patients with CD Dermatitis herpetiformis (DH) is a severe itchy blistering skin disease The rash usually occurs on the elbows knees and buttocks Although people with DH do not usually have digestive-tract symptoms they usually have the intestinal damage characteristic of CD

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Lactose Intolerance

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Lactose Intolerance

Lactose intolerance is the inability to break down a type of natural sugar called lactose

Lactose is commonly found in dairy products such as milk and yogurt

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Lactose Intolerance A person becomes lactose intolerant when

his or her small intestine stops making enough of the enzyme lactase to digest and break down the lactose

When this happens the undigested lactose moves into the large intestine The bacteria that are normally present in the large intestine interacts with the undigested lactose The condition may also be called lactase deficiency

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology Lactose a disaccharide is present in milk and

processed foods Dietary lactose must be hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa A deficiency of intestinal lactase prevents hydrolysis of ingested lactose The osmotic load of the unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit which increases the degree of maldigestion Within the large intestine free lactose is fermented by colonic bacteria to yield short-chain fatty acids and hydrogen gas The combined increase in fecal water intestinal transit and generated hydrogen gas accounts for the wide range of gastrointestinal symptoms

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Types of Lactose Intolerance

There are three main types of lactose intolerance

each with different causes

Primary Lactose Intolerance Secondary Lactose Intolerance Congenital or Developmental

Lactose Intolerance

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Primary Lactose Intolerance

This is the most common type of lactose intolerance

Most people are born with enough lactase Babies need the enzyme in order to digest their motherrsquos milk However the amount of lactase a person makes may decrease over time This is because as people age they eat a more diverse diet and rely less on milk

The decline in lactase is gradual This type of lactose intolerance is more common in people with Asian African Native American or Mediterranean ancestry

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Secondary Lactose Intolerance

Intestinal diseases such as celiac disease and inflammatory bowel disease or a surgery or injury to your small intestine can also cause lactose intolerance Lactase levels may be restored if the underlying disorder is treated

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Congenital or Developmental Lactose Intolerance

In very rare cases lactose intolerance is inherited A defective gene can be passed from the parents to a child resulting in the complete absence of lactase in the child This is referred to as congenital lactose intolerance

The baby will be intolerant of his or her motherrsquos milk He or she will have diarrhea as soon as human milk or a formula containing lactose is introduced If it is not recognized and treated early on the condition can be life threatening

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Developmental Lactose Intolerance

Occasionally a type of lactose intolerance called developmental lactose intolerance occurs when a baby is born prematurely This is because lactase production in the fetus begins later in the pregnancy after at least 34 weeks

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Epidemiology Primary lactase deficiency - 70 of the worlds

population Prevalence varies with ethnicity - eg 2 in Northern Europeans and up to 80 in Hispanic populations

Age of presentation also varies - eg Hispanic Asian and Afro-Caribbean children present before the age of 5 years whereas Northern Europeans usually present after the age of 5

Lactose intolerance in adults is very common and lactose may be found in many unexpected sources These include saccharine processed meats bread cake mixes soft drinks and lagers This may account for unexplained symptoms including some cases of irritable bowel disease

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Causes

Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare

Primary lactose intolerance is due to low levels of lactase which develop after childhood

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Causes Secondary or acquired lactase deficiency may develop in a person

with a healthy small intestine during episodes of acute illness This occurs because of mucosal damage or from medications Some causes of secondary lactase deficiency are as follows

Acute gastroenteritis Giardiasis Crohn disease Celiac sprue Tropical sprue Radiation enteritis Diabetic gastropathy Carcinoid syndrome Whipple syndrome HIV enteropathy Chemotherapy Gastrinoma

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk factors

Symptoms are caused only by the ingestion of lactose found in milk and other dairy products They are affected by the amount of lactose ingested and how fast the small intestine is presented with the lactose load They will be more marked if the lactose reaches the intestinal mucosa fast but less so if gastric emptying is delayed as by being ingested with a large meal Degree of symptoms is also affected by individual sensitivity and colonic flora

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Presentation

Symptoms result from reduced absorption of lactose which is then broken down by intestinal bacteria leading to gas and short-chain fatty acids

Gas build up causes Bloating Flatulence Abdominal discomfort

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The acidic and osmotic effects of undigested lactose may cause

Loose watery stool - with a degree of urgency an hour or two after ingestion of milk

Perianal itching due to acidic stools

Symptoms occur from one to several hours after ingestion of milk or dairy products These symptoms are very nonspecific and occur with other disorders such as milk-protein sensitivity allergic-type reactions to other substances in the meal or intolerance of other saccharides

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Whipple Disease

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Whipplersquos Disease

Whipples disease is a rare bacterial infection that most often affects your gastrointestinal system Whipples disease interferes with normal digestion by impairing the breakdown of foods such as fats and carbohydrates and hampering your bodys ability to absorb nutrients

Whipples disease also can infect other organs including your brain heart joints and eyes

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Causes

The cause of Whipples disease is infection with the bacterium Tropheryma whipplei

This bacterium initially affects the mucosal lining of your small intestine forming small lesions within the intestinal wall The bacterium also damages the fine hair-like projections (villi) that line the small intestine

With time the infection can spread to other parts of your body

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

The bacteria will lead to the development of internal sores and cause body tissue to thicken

When the villi (finger-like tissues that absorb nutrients in the small intestine) begin to thicken their natural shape begins to change This damages the villi and prevents them from effectively absorbing nutrients This in turn leads to many of the symptoms connected with Whipplersquos

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Whipples Disease showing macrophages in the small intestine

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk factors

Because so little is known about the bacterium that causes Whipples disease risk factors for the disease havent been clearly identified Based on available reports it appears more likely to affect

Middle-age and older individuals Males more than females Caucasian patients Family clusters (suggesting an immunogenetic

component) HLA-B27 antigen HLA-DRB113 and DQB106

alleles Sewage plant workers farmers and agricultural

workers

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Symptoms Associated With Whipplersquos Disease

Because it causes your body to be unable to properly absorb nutrients Whipplersquos disease affects many different parts of the body and is associated with a variety of symptoms

In advanced disease the infection may spread from the intestines to other organs such as the heart lungs brain joints and eyes

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Common signs and symptoms

Gastrointestinal signs and symptoms are common in Whipples disease and may include

Diarrhea Abdominal cramping and pain which

may worsen after meals Weight loss associated with the

malabsorption of nutrients

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Other frequent signs and symptoms associated with Whipples disease include

Inflamed joints particularly your ankles knees and wrists

Fatigue Weakness Anemia

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Less common signs and symptoms

In some cases signs and symptoms of Whipples disease may include

Fever Cough Enlarged lymph nodes Skin darkening (hyperpigmentation) in

areas exposed to the sun and in scars Chest pain Enlarged spleen

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Neurological signs and symptoms may include

Difficulty walking Visual impairment including lack of

control of eye movements Seizures Confusion Memory loss

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications The lining of your small intestine has fine hair-

like projections (villi) that help your body absorb nutrients Whipples disease damages the villi impairing nutrient absorption Nutritional deficiencies are common in people with Whipples disease and can lead to fatigue weakness weight loss and joint pain

Whipples disease is a progressive and potentially fatal disease Although the infection is rare associated deaths continue to be reported due in large part to late diagnoses and delayed treatment Death often is caused by the spread of the infection to the central nervous system which can cause irreversible damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Tropical Sprue

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Tropical Sprue

Tropical sprue is caused by inflammation of your intestines This swelling makes it more difficult for you to absorb nutrients from food

People with tropical sprue do not absorb nutrients properly especially vitamin B12 and folic acid

Normal small intestines have fingerlike projections called villi that provide more surface area for nutrients to be absorbed In people with tropical sprue these villi are flattened making absorption difficult

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology The exact role of microbial agents in the

initiation and propagation of the disease is poorly understood One theory is that an acute intestinal infection leads to jejunal and ileal mucosa injury then intestinal bacterial overgrowth and increased plasma enteroglucagon results in retardation of small-intestinal transit Central to this process is folate deficiency which probably contributes to further mucosal injury

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Hormone enteroglucagon and motilin levels are elevated in patients with tropical sprue Enterocyte injury can cause these elevations Enteroglucagon causes intestinal stasis but the role of motilin is not clear

The upper small intestine is predominantly affected however because it is a progressive and contiguous disease the distal small intestine up to the terminal ileum may be involved Pathological changes are rarely demonstrated in the stomach and colon Coliform bacteria such as Klebsiella E coli and Enterobacter species are isolated and are the usual organisms associated with tropical sprue

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

What Causes Tropical Sprue

Tropical sprue is rare unless you live in or visit tropical areas

Researchers believe the condition is caused by an overgrowth of bacteria in your intestines The specific bacteria that cause tropical sprue are unknown

You may be at risk for tropical sprue if you live in a tropical area have traveled through a tropical area for a

long period of time

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Epidemiology

Tropical sprue usually occurs in residents of tropical or subtropical usually in developing countries

The incidence varies considerably with geography

It occurs mostly in South East Asia and the Caribbean

There is no predilection for race or gender It tends to affect adults but can also occur in

children The condition may present in natives or travellers

and may not present until after they have left the area

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

What Are the Symptoms of Tropical Sprue

Symptoms of tropical sprue may include any of the following

abdominal cramps diarrhea which may get worse on a high-fat diet excessive gas indigestion irritability muscle cramps numbness paleness weight loss

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Short Bowel Syndrome

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Short Bowel Syndrome

Short bowel syndrome is a complication that can occur in people who have a large part or all of their small intestine removed

Short bowel syndrome (SBS) a disorder characterized by diarrhea malabsorption fluid and electrolyte disturbances and eventually malnutrition

Short bowel syndrome may be present at birth due to a congenital anomaly or may develop in older infants and children as a result of disease or trauma occurring later in life

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Etiology of Short Bowel Syndrome

Short bowel syndrome may be a congenital oracquired condition Infants may be born with congenital jejunal or ileal atresia

Otherwise short bowel syndrome results from surgical resection of bowel This is usually related to multiple resections for recurrent Crohnrsquos disease massive enterectomy made necessary because of acatastrophic vascular event such as mesenteric arterialembolism venous thrombosis volvulus trauma or tumorresection in adults and in children gastroschisis necrotizing enterocolitis (NEC) and volvulus

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk Factors

Factors that may increase your risk of short bowel syndrome include

Crohns disease which is the most common reason for the removal of the small intestine

Vascular problems Premature birth or very low birth weight Necrotizing enterocolitis Intestinal atresias Gastroschesis

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Symptoms

Symptoms of short bowel syndrome may include

Diarrhea Cramping Bloating Heartburn Malnourishment Poor growth Dehydration Weakness Fatigue Depression Weight loss Food sensitivities

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Inflammatory Bowel Disease

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Inflammatory Bowel Disease

Inflammatory Bowel Diseases (IBD) is a broad term that describes conditions with chronic or recurring immune response and inflammation of the gastrointestinal tract The two most common inflammatory bowel diseases are ulcerative colitis and Crohnrsquos disease

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Both illnesses have one strong feature in common They are marked by an abnormal response by the bodyrsquos immune system

Normally the immune cells protect the body from infection In people with IBD however the immune system mistakes food bacteria and other materials in the intestine for foreign substances and it attacks the cells of the intestines

In the process the body sends white blood cells into the lining of the intestines where they produce chronic inflammation When this happens the patient experiences the symptoms of IBD

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Signs and Symptoms

Symptoms (Intestinal) include

Diarrhea Possible presence of mucusblood in stool occurs at night

Constipation May be the primary symptom in UC and limited to rectum obstipation may occur may proceed to bowel obstruction

Bowel movement abnormalities Possible presence of pain or rectal bleeding severe urgency tenesmus

Abdominal cramping and pain Commonly present in the right lower quadrant in CD

Nausea and vomiting More often in CD than in UC

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Signs and Symptoms

Systemic symptoms include

Cramping Irregular bowel habits passage of mucus without

blood or pus Weight loss Fever sweats Fatigue Arthralgias Growth Grossly bloody stools Perianal disease (eg fistulas abscesses)

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology

In several studies genetic factors appeared to influence the risk of inflammatory bowel disease (IBD) by causing a disruption of epithelial barrier integrity deficits in autophagydeficiencies in innate pattern recognition receptors and problems with lymphocyte differentiation

The immune response disrupts the intestinal mucosa and leads to a chronic inflammatory process

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Etiology

Three characteristics define the etiology of inflammatory bowel disease (IBD)

Genetic predisposition An altered dysregulated immune

response An altered response to gut

microorganisms

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Epidemiology of the IBD

The peak age of onset for IBD is 15 to 30 years old although it may occur at any age About 10 of cases occur in individuals younger than 18 years

Ulcerative colitis is slightly more common in males whereas Crohnrsquos disease is marginally more frequent in women

IBD occurs more in people of Caucasian and Ashkenazic Jewish origin than in other racial and ethnic subgroups

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications of IBD disease

Intestinal complications

IBD can be associated with several gastrointestinal complications including risk of hemorrhage perforation strictures and fistulasmdashas well as perianal disease and related complications such as perianal or pelvic abscesses toxic megacolon and malignancy (colorectal cancer cholangiocarcinoma)

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications of IBD disease

Extra intestinal complications

Extra intestinal complications include

Osteoporosis Hypercoagulability Anemia Gallstones Aphthous ulcers Iritis (uveitis) Episcleritis Skin complications

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Extra intestinal manifestations of inflammatory diseases of intestine

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Ulcerative Colitis

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Ulcerative Colitis (UC)

Ulcerative colitis is an inflammatory bowel disease (IBD) that causes long-lasting inflammation in part of your digestive tract

ulcerative colitis can be debilitating and sometimes can lead to life-threatening complications Because ulcerative colitis is a chronic condition symptoms usually develop over time rather than suddenly

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Ulcerative colitis usually affects only the innermost lining of your large intestine (colon) and rectum It occurs only through continuous stretches of your colon unlike Crohns disease which occurs anywhere in the digestive tract and often spreads deeply into the affected tissues

Theres no known cure for ulcerative colitis but therapies are available that may dramatically reduce the signs and symptoms of ulcerative colitis

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Symptoms

Ulcerative colitis symptoms can vary depending on the severity of inflammation and where it occurs For these reasons doctors often classify ulcerative colitis according to its location

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Symptoms

Here are the signs and symptoms that may accompany ulcerative colitis depending on its classification

Ulcerative proctitis In this form of ulcerative colitis inflammation is confined to the area closest to the anus (rectum) and for some people rectal bleeding may be the only sign of the disease Others may have rectal pain and a feeling of urgency This form of ulcerative colitis tends to be the mildest

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Proctosigmoiditis This form involves the rectum and the lower end of the colon known as the sigmoid colon Bloody diarrhea abdominal cramps and pain and an inability to move the bowels in spite of the urge to do so (tenesmus) are common problems associated with this form of the disease

Left-sided colitis As the name suggests inflammation extends from the rectum up through the sigmoid and descending colon which are located in the upper left part of the abdomen Signs and symptoms include bloody diarrhea abdominal cramping and pain on the left side and unintended weight loss

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pancolitis Affecting more than the left colon and often the entire colon pancolitis causes bouts of bloody diarrhea that may be severe abdominal cramps and pain fatigue and significant weight loss

Fulminant colitis This rare life-threatening form of colitis affects the entire colon and causes severe pain profuse diarrhea and sometimes dehydration and shock People with fulminant colitis are at risk of serious complications including colon rupture and toxic megacolon a condition that causes the colon to rapidly expand

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology

Inflammation begins in the rectum and extends proximally in an uninterrupted fashion to the proximal colon and could eventually involve the entire length of the large intestine

The rectum is always involved in ulcerative colitis and unlike in Crohn disease there are no skip areas

Even with less than total colonic involvement the disease is strikingly and uniformly continuous As ulcerative colitis becomes chronic the colon becomes a rigid foreshortened tube leading to the lead-pipe appearance

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Causes

No one is quite sure what triggers ulcerative colitis but theres a consensus as to what doesnt Researchers no longer believe that stress is the main cause although stress can often aggravate symptoms Instead current thinking focuses on the following possibilities

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Immune system Some scientists think a virus or bacterium may trigger ulcerative colitis The digestive tract becomes inflamed when your immune system tries to fight off the invading microorganism (pathogen) Its also possible that inflammation may stem from an autoimmune reaction in which your body mounts an immune response even though no pathogen is present

Heredity Because youre more likely to develop ulcerative colitis if you have a parent or sibling with the disease scientists suspect that genetic makeup may play a contributing role However most people who have ulcerative colitis dont have a family history of this disorder

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Risk factors

Ulcerative colitis affects about the same number of women and men Risk factors may include

Age Ulcerative colitis usually begins before the age of 30 But it can occur at any age and some people may not develop the disease until their 50s or 60s

Race or ethnicity Although whites have the highest risk of the disease it can occur in any race If youre of Ashkenazi Jewish descent your risk is even higher

Family history Youre at higher risk if you have a close relative such as a parent sibling or child with the disease

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications

Possible complications of ulcerative colitis include Severe bleeding A hole in the colon (perforated colon) Severe dehydration Liver disease (rare) Kidney stones Osteoporosis Inflammation of your skin joints and eyes An increased risk of colon cancer A rapidly swelling colon (toxic megacolon)

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Crohnrsquos Disease

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Crohnrsquos Disease

Crohnrsquos disease is a condition of chronic inflammation potentially involving any location of the gastrointestinal tract but it frequently affects the end of the small bowel and the beginning of the large bowel

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Signs and Symptoms

Symptoms include

Persistent diarrhea Cramping Abdominal pain Fever Rectal bleeding Loss of appetite weight loss Fatigue

However the disease is not always limited to the gastrointestinal tract it can also affect the joints eyes skin and liver

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Pathophysiology

Crohn disease can affect any portion of the gastrointestinal tract from the mouth to the anus and causes 3 patterns of involvement inflammatory disease strictures and fistulas

The most important pathologic feature of Crohn disease is that it is transmural involving all layers of the bowel not just the mucosa and the submucosa which is characteristic of ulcerative colitis

Furthermore Crohn disease is discontinuous with skip areas interspersed between 2 or more involved areas

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Late in the disease the mucosa develops a cobblestone appearance which results from deep longitudinal ulcerations interlaced with intervening normal mucosa

Rectal sparing is a typical but not constant feature of Crohn disease However anorectal complications (eg fistulas abscesses) are common

Much less commonly Crohn disease involves the more proximal parts of the GI tract including the mouth tongue esophagus stomach and duodenum

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Complications

The most common complication of Crohnrsquos disease is blockage of the intestine due to swelling and scar tissue

Symptoms of blockage include cramping pain vomiting and bloating

Another complication is sores or ulcers within the intestinal tract Sometimes these deep ulcers turn into tractsmdashcalled fistulas

Patients may also develop a shortage of proteins calories or vitamins

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Cholelithiasis and Nephrolithiasis

The incidence of gallstones and kidney stones is increased in Crohn disease because of malabsorption of fat and bile salts

Gallstones are formed because of increased cholesterol concentration in the bile which is caused by a reduced bile salt pool

Patients who have Crohn disease with ileal disease or resection are also likely to form calcium oxalate kidney stones With the fat malabsorption unabsorbed long-chain fatty acids bind calcium in the lumen Oxalate in the lumen is normally bound to calcium Calcium oxalate is poorly soluble and poorly absorbed however if calcium is bound to malabsorbed fatty acids oxalate combines with sodium to form sodium oxalate which is soluble and is absorbed in the colon

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Crohnrsquos Disease amp Ulcerative

Colitis

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Localization of damage

Ulcerative Colitis Crohnrsquos Disease

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Volume of damage

Ulcerative Colitis Crohnrsquos Disease

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage

Depth of damage

Ulcerative Colitis Crohnrsquos Disease

• Malabsorption Syndrome
• The Gastrointestinal (GI) Tract amp Absorption
• Malabsorption Syndrome (2)
• Malabsorption Syndrome (3)
• Slide 5
• Pathophysiology (Mechanism)
• Slide 7
• Slide 8
• Causes of Malabsorption Syndrome
• The Luminal Phase
• The Luminal Phase (2)
• Slide 12
• Slide 13
• Slide 14
• Mucosal phase
• Mucosal phase (2)
• Mucosal phase (3)
• Mucosal phase (4)
• Slide 19
• Post - absorptive Phase
• External Causes
• Risk Factors
• Symptoms of Malabsorption Syndrome
• Slide 24
• Slide 25
• Slide 26
• Slide 27
• Slide 28
• Slide 29
• Slide 30
• Slide 31
• Slide 32
• Physical Signs of Malabsorption
• Slide 34
• Slide 35
• Possible Complications
• Celiac Disease
• Celiac Disease (2)
• Slide 39
• Slide 40
• Slide 41
• Slide 42
• Risk Factors for Celiac Disease
• Pathogenesis
• Slide 45
• Slide 46
• Slide 47
• Slide 48
• Slide 49
• Slide 50
• Slide 51
• Slide 52
• Epidemiology
• Clinical Presentations
• Slide 55
• Slide 56
• Gastrointestinal Symptoms
• Gastrointestinal Symptoms (2)
• Gastrointestinal Symptoms (3)
• Extra - Intestinal Symptoms
• Extra - Intestinal Symptoms (2)
• Extra - Intestinal Symptoms (3)
• Physical
• Physical (2)
• Associated conditions
• Slide 66
• Slide 67
• Slide 68
• Lactose Intolerance
• Lactose Intolerance (2)
• Lactose Intolerance (3)
• Pathophysiology
• Slide 73
• Types of Lactose Intolerance
• Primary Lactose Intolerance
• Secondary Lactose Intolerance
• Congenital or Developmental Lactose Intolerance
• Developmental Lactose Intolerance
• Epidemiology (2)
• Causes
• Causes (2)
• Risk factors
• Presentation
• Slide 84
• Whipple Disease
• Whipplersquos Disease
• Causes (3)
• Slide 88
• Slide 89
• Risk factors (2)
• Symptoms Associated With Whipplersquos Disease
• Common signs and symptoms
• Slide 93
• Less common signs and symptoms
• Slide 95
• Complications
• Tropical Sprue
• Tropical Sprue (2)
• Pathophysiology (2)
• Slide 100
• What Causes Tropical Sprue
• Epidemiology (3)
• Slide 103
• What Are the Symptoms of Tropical Sprue
• Short Bowel Syndrome
• Short Bowel Syndrome
• Slide 107
• Etiology of Short Bowel Syndrome
• Risk Factors
• Symptoms
• Complications (2)
• Inflammatory Bowel Disease
• Inflammatory Bowel Disease
• Slide 114
• Slide 115
• Signs and Symptoms
• Signs and Symptoms (2)
• Pathophysiology (3)
• Etiology
• Epidemiology of the IBD
• Complications of IBD disease
• Complications of IBD disease (2)
• Extra intestinal manifestations of inflammatory diseases of int
• Ulcerative Colitis
• Ulcerative Colitis (UC)
• Slide 126
• Symptoms
• Symptoms (2)
• Slide 129
• Slide 130
• Pathophysiology (4)
• Causes (4)
• Slide 133
• Risk factors (3)
• Complications (3)
• Slide 136
• Crohnrsquos Disease
• Crohnrsquos Disease (2)
• Slide 139
• Signs and Symptoms (3)
• Pathophysiology (5)
• Slide 142
• Slide 143
• Complications (4)
• Slide 145
• Cholelithiasis and Nephrolithiasis
• Crohnrsquos Disease amp Ulcerative Colitis
• Slide 148
• Slide 149
• Localization of damage
• Volume of damage
• Depth of damage