1. Inflammatory Bowel Disease (IBD)
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Transcript of 1. Inflammatory Bowel Disease (IBD)
1. Inflammatory Bowel Disease (IBD)
Goals:learning 1. Inflammatory Bowel Disease (IBD) Definition
Epidemiology Etiology and Pathogenesis Pathology Clinical
Presentation Laboratory, Endoscopic, and Radiographic Features
Extraintestinal Manifestations Complications Treatment 2. Irritable
Bowel Syndrome (IBS) Clinical Feature Pathophysiology Inflammatory
Bowel Disease (IBD)
Definition Inflammatory bowel disease (IBD) is an immune-mediated
chronic intestinal condition. Ulcerative colitis (UC) and Crohn's
disease (CD) are the two major types of IBD. Inflammatory bowel
disease (IBD)
Epidemiology The incidence of IBD varies within different
geographic areas. CD and UC both occur at the highest incidence in
Europe, the United Kingdom, and North America. IBD has been rare in
other areas except Israel, Australia, and South Africa. The
incidence of IBD, especially UC, is rising in Japan, South Korea,
Singapore, northern India, and Latin America, areas previously
thought to have low incidence. The highest mortality is during the
first years of disease and in long-duration disease due to the risk
of colon cancer. The peak age of onset of UC and CD is between 15
and 30 years. A second peak occurs between the ages of 60 and 80.
The male to female ratio for UC is 1:1 and for CD is 1.11.8:1.
Inflammatory bowel disease (IBD)
Etiology and Pathogenesis A consensus hypothesis is that in
genetically predisposed individuals, both exogenous factors (e.g.,
composition of normal intestinal microbiota) and endogenous host
factors (e.g., intestinal epithelial cell barrier function, innate
and adaptive immune function) interact to cause a chronic state of
dysregulated mucosal immune function that is further modified by
specific environmental factors (e.g., smoking, enteropathogens).
IBD is currently considered an inappropriate immune response to the
endogenous commensal microbiota within the intestines, with or
without some component of autoimmunity. Inflammatory bowel disease
(IBD)
Pathology Macroscopic Features Microscopic Features Ulcerative
Colitis inflammation and erythematous mucosa. In more severe
disease, the mucosa is hemorrhagic, edematous, and ulcerated 4050%
of patients have disease limited to the rectum and rectosigmoid,
3040% have disease extending beyond the sigmoid but not involving
the whole colon, and 20% have a total colitis. The process is
limited to the mucosa and superficial submucosa, with deeper layers
unaffected except in fulminant disease. Crohn's Disease any part of
the GI tract from the mouth to the anus.3040% of patients have
small bowel disease alone, 4055% have disease involving both the
small and large intestines, and 1525% have colitis alone. Unlike
UC, the rectum is often spared. CD is segmental with skip areas in
the midst of diseased intestine . aphthoid ulcerations and focal
crypt abscesses, noncaseating granulomas in all layers of the bowel
wall . Inflammatory bowel disease (IBD)
Clinical Presentation Ulcerative Colitis The major symptoms of UC
are diarrhea, rectal bleeding, tenesmus, passage of mucus, and
crampy abdominal pain. Although UC can present acutely, symptoms
usually have been present for weeks to months. Diarrhea is often
nocturnal and/or postprandial. Other symptoms in moderate to severe
disease include anorexia, nausea, vomiting, fever, and weight loss.
Inflammatory bowel disease (IBD)
Clinical Presentation Crohn's Disease The site of disease
influences the clinical manifestations. Ileocolitis Because the
most common site of inflammation is the terminal ileum, the usual
presentation of ileocolitis is a chronic history of recurrent
episodes of right lower quadrant pain and diarrhea. Pain is usually
colicky; it precedes and is relieved by defecation. A low-grade
fever is usually noted. Weight loss is commontypically 1020% of
body weightand develops as a consequence of diarrhea, anorexia, and
fear of eating. Jejunoileitis Extensive inflammatory disease is
associated with a loss of digestive and absorptive surface,
resulting in malabsorption and steatorrhea. Nutritional
deficiencies can also result from poor intake and enteric losses of
protein and other nutrients. Intestinal malabsorption can cause
anemia, hypoalbuminemia, hypocalcemia, hypomagnesemia,
coagulopathy, and hyperoxaluria with nephrolithiasis in patients
with an intact colon. Inflammatory bowel disease (IBD)
Clinical Presentation Crohn's Disease (continued) Colitis and
Perianal Disease Patients with colitis present with low-grade
fevers, malaise, diarrhea, crampy abdominal pain, and sometimes
hematochezia. Gross bleeding is not as common as in UC and appears
in about one-half of patients with exclusively colonic disease.
Only 12% bleed massively. Gastroduodenal Disease Symptoms and signs
of upper GI tract disease include nausea, vomiting, and epigastric
pain. Patients usually have an Helicobacter pylorinegative
gastritis. The second portion of the duodenum is more commonly
involved than the bulb. Inflammatory bowel disease (IBD)
Laboratory, Endoscopic, and Radiographic Features Ulcerative
Colitis Active disease can be associated with a rise in acute-phase
reactants [C-reactive protein (CRP)], platelet count, erythrocyte
sedimentation rate (ESR), and a decrease in hemoglobin. Fecal
lactoferrin is a highly sensitive and specific marker for detecting
intestinal inflammation. Diagnosis relies upon the patient's
history; clinical symptoms; negative stool examination for
bacteria, C. difficile toxin, and ova and parasites; sigmoidoscopic
appearance; and histology of rectal or colonic biopsy specimens.
Inflammatory bowel disease (IBD)
Laboratory, Endoscopic, & Radiographic Features Crohn's Disease
Laboratory abnormalities include elevated ESR and CRP. In more
severe disease, findings include hypoalbuminemia, anemia, and
leukocytosis. Endoscopic features of CD include rectal sparing,
aphthous ulcerations, fistulas, and skip lesions. Colonoscopy
allows examination and biopsy of mass lesions or strictures and
biopsy of the terminal ileum. Upper endoscopy is useful in
diagnosing gastroduodenal involvement in patients with upper tract
symptoms. Inflammatory bowel disease (IBD)
Extraintestinal Manifestations Up to one-third of IBD patients have
at least one extraintestinal disease manifestation. Dermatologic
Erythema nodosum (EN): The lesions of EN are hot, red, tender
nodules measuring 15 cm in diameter and are found on the anterior
surface of the lower legs, ankles, calves, thighs, and arms.
Rheumatologic Peripheral arthritis is more common in CD. It is
asymmetric, polyarticular, and migratory and most often affects
large joints of the upper and lower extremities. Ocular The most
common are conjunctivitis, anterior uveitis/iritis, and
episcleritis. Inflammatory bowel disease (IBD)
Extraintestinal manifestations Hepatobiliary Hepatic steatosis:
patients usually present with hepatomegaly. Fatty liver, and
cholelithiasis are seen. Urologic The most frequent genitourinary
complications are calculi, ureteral obstruction, and ileal bladder
fistulas. Metabolic Bone Disorders Low bone mass occurs in 330% of
IBD patients. The risk is increased by glucocorticoids,
cyclosporine, methotrexate and total parenteral nutrition (TPN).
Thromboembolic Disorders Patients with IBD have an increased risk
of both venous and arterial thrombosis even if the disease is not
active. Inflammatory bowel disease (IBD)
Treatment 5-ASA Agents The mainstay of therapy for mild to moderate
UC is sulfasalazine and the other 5-ASA agents. These agents are
effective at inducing and maintaining remission in UC. They may
have a limited role in inducing remission in CD but no clear role
in maintenance of CD. Sulfasalazine can impair folate absorption,
and patients should be given folic acid supplements. Newer
sulfa-free aminosalicylate preparations deliver increased amounts
of the pharmacologically active ingredient of sulfasalazine (5-ASA,
mesalamine) to the site of active bowel disease while limiting
systemic toxicity. Asacol is an enteric-coated form of mesalamine
with the 5-ASA being released at pH >7. Inflammatory bowel
disease (IBD)
Treatment (continued) Glucocorticoids The majority of patients with
moderate-to-severe UC and CD benefit from oral or parenteral
glucocorticoids. Antibiotics Metronidazole is effective in active
inflammatory, fistulous, and perianal CD and may prevent recurrence
after ileal resection. Ciprofloxacin is also beneficial.
Azathioprine and 6-Mercaptopurine They are purine analogues
commonly employed in the management of glucocorticoid-dependent
IBD. Cyclosporine Cyclosporine (CSA) has the inhibitory effects on
both the cellular and humoral immune systems. Inflammatory bowel
disease (IBD)
Treatment (continued) Nutritional Therapies Dietary antigens may
stimulate the mucosal immune response. Patients with active CD
respond to bowel rest, along with TPN. Bowel rest and TPN are as
effective as glucocorticoids at inducing remission of active CD.
Enteral nutrition in the form of elemental or peptide-based
preparations is also as effective as glucocorticoids or TPN, but
these diets are not palatable. Enteral diets may provide the small
intestine with nutrients vital to cell growth and do not have the
complications of TPN. In contrast to CD, dietary intervention does
not reduce inflammation in UC. Irritable bowel syndrome (IBS)
Definition Irritable bowel syndrome (IBS) is a functional bowel
disorder characterized by abdominal pain or discomfort and altered
bowel habits in the absence of detectable structural abnormalities.
No clear diagnostic markers exist for IBS, thus the diagnosis of
the disorder is based on clinical presentation. Throughout the
world, about 1020% of adults and adolescents have symptoms
consistent with IBS, and most studies show a female predominance.
IBS symptoms tend to come and go over time and often overlap with
other functional disorders such as fibromyalgia, headache,
backache, and genitourinary symptoms. Severity of symptoms varies
and can significantly impair quality of life, resulting in high
health care costs. Irritable bowel syndrome (IBS)
Clinical Features Symptoms include: 1. Pain or abdominal
discomfort: is a key symptom for the diagnosis of IBS. (Pain is
often exacerbated by eating or emotional stress and improved by
passage of flatus or stools.) 2. Painless diarrhea or constipation
: alteration in bowel habits is the most consistent clinical
feature in IBS 3. Urgency or a feeling of incomplete bowel
movement, 4. Bloating : Patients with IBS frequently complain of
abdominal distention and increased belching or flatulence.
(Although some patients with these symptoms actually may have a
larger amount of gas, quantitative measurements reveal that most
patients who complain of increased gas generate no more than a
normal amount of intestinal gas.) Irritable bowel syndrome
(IBS)
Clinical Features (continued) 5.Upper gastrointestinal symptoms
(Between 25 and 50% of patients with IBS complain of dyspepsia,
heartburn, nausea, plus vomiting.) Sleep deprivation is also
unusual because abdominal pain is almost uniformly present only
during waking hours. However, patients with severe IBS frequently
wake repeatedly during the night; thus, nocturnal pain is a poor
discriminating factor between organic and functional bowel disease.
In addition, female patients with IBS commonly report worsening
symptoms during the premenstrual and menstrual phases. Irritable
bowel syndrome (IBS)
Pathophysiology 1. Gastrointestinal motor abnormalities : IBS
patients may exhibit increased rectosigmoid motor activity for up
to 3 h after eating. 2. Visceral hypersensitivity : IBS patients
frequently exhibit exaggerated sensory responses to visceral
stimulation. 3. Central neural dysregulation : The role of central
nervous system (CNS) factors in the pathogenesis of IBS is strongly
suggested by the clinical association of emotional disorders and
stress with symptom exacerbation and the therapeutic response to
therapies that act on cerebral cortical sites. 4. Abnormal
psychological features : Abnormal psychiatric features are recorded
in up to 80% of IBS patients; however, no single psychiatric
diagnosis predominates. Irritable bowel syndrome (IBS)
Pathophysiology 5. Post-infectious IBS : IBS may be induced by GI
infection. This group of "postinfective" IBS occurs more commonly
in females and affects younger rather than older patients. The
microbes involved in the initial infection are Campylobacter,
Salmonella, and Shigella. 6. Mucosal inflammation : Some patients
with IBS display persistent signs of low-grade mucosal inflammation
with activated lymphocytes, mast cells, and enhanced expression of
proinflammatory cytokines. 7. Altered gut flora : A high prevalence
of small intestinal bacterial overgrowth in IBS patients has been
noted. 8. Abnormal Serotonin Pathways : The serotonin
(5HT)-containing enterochromaffin cells in the colon are increased
in a subset of IBS-D patients compared to healthy individuals or
patients with ulcerative colitis. Irritable bowel syndrome
(IBS)
Treatment Patient counseling & Dietary alterations Reassurance
and careful explanation of how to avoid obvious food precipitants
are important first steps in patient counseling and dietary change.
Occasionally, a meticulous dietary history may reveal substances
(such as coffee, disaccharides, legumes, and cabbage) that
aggravate symptoms. Excessive fructose and artificial sweeteners,
such as sorbitol or mannitol, may cause diarrhea, bloating,
cramping or flatulence. As a therapeutic trial, patients should be
encouraged to eliminate any foodstuffs that appear to produce
symptoms. However patients should avoid nutritionally depleted
diets. Irritable bowel syndrome (IBS)
Treatment (continued) Patient counseling & Dietary alterations
(continued) Patients with IBS-D anecdotally report symptom
improvement after initiating a low-carbohydrate diet. A prospective
study has shown marked symptomatic improvement in stool frequency,
consistency, pain scores, and quality of life following 4 weeks of
a very-low-carbohydrate (CHO) diet (20 g CHO/day). This diet may be
tried in IBS patients who report intolerance to certain
carbohydrates. Irritable bowel syndrome (IBS)
Treatment (continued) Stool-bulking agents High-fiber diets and
bulking agents, such as bran, are frequently used in treating IBS.
The water-holding action of fibers may contribute to increased
stool bulk because of the ability of fiber to increase fecal output
of bacteria. Fiber also speeds up colonic transit in most persons.
In diarrhea-prone patients, whole-colonic transit is faster than
average; however, dietary fiber can delay transit. Furthermore,
because of their hydrophilic properties, stool-bulking agents bind
water and thus prevent both excessive hydration and dehydration of
stool. The latter observation may explain the clinical experience
that a high-fiber diet relieves diarrhea in some IBS patients.
Irritable bowel syndrome (IBS)
Treatment (continued) Stool-bulking agents (continued) Fiber
supplementation with psyllium has been shown to reduce perception
of rectal distention, indicating that fiber may have a positive
effect on visceral afferent function. psyllium produced greater
improvements in stool pattern and abdominal pain than bran.
Furthermore, psyllium preparations tend to produce less bloating
and distention. Despite the equivocal data regarding efficacy, most
gastroenterologists consider stool-bulking agents worth trying in
patients with IBS-C. Irritable bowel syndrome (IBS)
Treatment (continued) Antispasmodics Clinicians have observed that
anticholinergic drugs may provide temporary relief for symptoms
such as painful cramps related to intestinal spasm. Some physicians
prefer to use synthetic anticholinergics such as dicyclomine that
have less effect on mucous membrane secretions and produce fewer
undesirable side effects. Antidiarrheal agents Peripherally acting
opiate-based agents are the initial therapy of choice for IBS-D.
When diarrhea is severe, especially in the painless diarrhea
variant of IBS, small doses of loperamide, 24 mg every 46 h up to a
maximum of 12 g/d, can be prescribed. These agents are less
addictive than paregoric, codeine, or tincture of opium. Irritable
bowel syndrome (IBS)
Treatment (continued) Antidepressant drugs In addition to their
mood-elevating effects, antidepressant medications have several
physiologic effects that suggest they may be beneficial in IBS. In
IBS-D patients, the tricyclic antidepressantimipramine slows
jejunal migrating motor complex transit propagation and delays
orocecal and whole-gut transit, indicative of a motor inhibitory
effect. Irritable bowel syndrome (IBS)
Treatment (continued) Antiflatulence therapy Patients should be
advised to eat slowly and not chew gum or drink carbonated
beverages. If bloating is accompanied by diarrhea and worsens after
ingesting dairy products, fresh fruits, vegetables, or juices,
further investigation or a dietary exclusion trial may be
worthwhile. Antibiotics may help in a subgroup of IBS patients with
predominant symptoms of bloating. Pancreatic enzymes reduce
bloating, gas, and fullness during and after high-calorie, high-fat
meal ingestion. Irritable bowel syndrome (IBS)
Treatment (continued) Modulation of Gut Flora Antibiotic treatment
benefits a subset of IBS patients. Neomycin dosed at 500 mg twice
daily for 10 days was more effective. The non-absorbed oral
antibiotic rifaximin is the most thoroughly studied antibiotic for
the treatment of IBS. Rifaximin is the only antibiotic with
demonstrated sustained benefit beyond therapy cessation in IBS
patients. Since altered colonic flora may contribute to the
pathogenesis of IBS, this has led to great interest in using
probiotics to naturally alter the flora. Bifidobacterium infantis
showed significant improvement in the composite score for abdominal
pain, bloating/distention, and/or bowel movement compared with
placebo in two placebo-controlled trials. Inflammatory bowel
disease (IBD)
Some mechanisms for further information The highest frequency of
nephrolithiasis (1020%) occurs in patients with CD following small
bowel resection. Calcium oxalate stones develop secondary to
hyperoxaluria, which results from increased absorption of dietary
oxalate. Normally, dietary calcium combines with luminal oxalate to
form insoluble calcium oxalate, which is eliminated in the stool.
In patients with ileal dysfunction, however, nonabsorbed fatty
acids bind calcium and leave oxalate unbound. The unbound oxalate
is then delivered to the colon, where it is readily absorbed,
especially in the presence of inflammation.