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OUR LADY OF FATIMA UNIVERSITY

Fatima College of Medicine

Department of Biochemistry and Nutrition

BIOCHEMICAL ASPECTS OF

DIARRHOEA

BARSAGA, Mark Lester

BASILLO, Rhealyn

BAUI, Bernard Jr.

BANAS, Philip Gideon

BELADA, Ralph PatrickSection A2, Group 1

Second Semester S.Y. 2010 2011

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OBJECTIVES

After the discussion, the students will be able toknow the biochemical aspects of diarrhea.

Specifically, they will

know the definition of diarrhea identify common causes and differentiate types

of diarrhea

understand the treatment and management ofdiarrhea

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DIARRHOEA

It is the passage of 3 or more loose or liquid

stools per day, or more frequently than is

normal for the individual (WHO)

It is usually a symptom of gastrointestinal

infection, which can be caused by a varietyof bacterial, viral and parasitic organisms.

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DIARRHOEA

Infection is spread through contaminated

food or drinking-water, or from person to

person as a result of poor hygiene.

Severe diarrhoea leads to fluid loss

(dehydration), and may be life-threatening,

particularly in young children and people

who are malnourished or have impaired

immunity.

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Diarrhoeal disease is the second leading cause of deathin children under five years old. It is both preventable

and treatable.

Diarrhoeal disease kills 1.5 million children every year.

Globally, there are about two billion cases of diarrhoeal

disease every year.

Diarrhoeal disease mainly affects children under twoyears old.

Diarrhoea is a leading cause of malnutrition in children

under five years old.

Key facts (WHO, August 2009)

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INFANT MORTALITY: TEN (10) LEADING CAUSES NUMBER AND

RATE/per 1000 live births AND PERCENTAGE DISTRIBUTION,

Philippines, 2005 (DOH)

Cause Number Rate Percent

1. Bacterial sepsis of newborn 3,161 1.9 14.6

2. Respiratory distress of newborn 2,298 1.4 10.6

3. Pneumonia 2,013 1.2 9.3

4. Disorders related to short gestation and low birth

weight, not elsewhere classified1,610 1 7.4

5. Congenital Pneumonia 1,510 0.9 7

6. Congenital malformation of the heart 1,444 0.9 6.7

7. Neonatal aspiration syndrome 1,146 0.7 5.3

8. Other congenital malformation 1,012 0.6 4.7

9. Intrauterine hypoxia and birth asphyxia 971 0.6 4.5

10.Diarrhea and gastro-enterities of presumed

infectious origin 900 0.5 4.2

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Ten (10) Leading Causes of Child Mortality By Age-Group (1-4) &

Sex No. & Rate/100,000 population, Philippines,(Source: Philippine Health Statistics 2000, DOH)

Cause1-4 Years

Male Female Both Rate

1. Pneumonia 1,540 1,341 2,881 37.76

2. Accidents 839 506 1,345 17.63

3. Diarrheas and gastoenteritisof presumed infectious origin

685 546 1,231 16.14

4. Measles 452 425 877 11.50

5. Congenital anomalies 350 337 687 9.01

6. Malignant Neoplasm 219 153 372 4.88

7. Meningitis 201 155 356 4.67

8. Septicemia 173 173 346 4.54

9. Chronic obstructive pulmonarydisease and allied conditions

174 164 338 4.43

10. Other protein-caloriemalnutrition 175 159 334 4.38

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CLASSIFICATION OF

DIARRHEA

BANAS, Philip Gideon

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CLASSIFICATION OF DIARRHEA

1. Acute Diarrhea

2. Chronic Diarrheaa. Watery

i. Osmotic

ii. Secretoryb. Inflammatory

c. Fatty

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CLASSIFICATION OF

DIARRHEA: ACUTE DIARRHEA

Lasting less than 4 weeks

Cause by infections and are self limiting

Viruses (adenovirus and rotavirus)

Bacteria (salmonella, shigella, Escherichia colli)

Protozoa (giardia lamblia and entamoebahistolytica)

Consumption of potentially contaminated foodand drinks is another risk factor for infectious

diarrhea

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Pathogenic infections cause

diarrhea by one or four mechanisms

Enterotoxins that subvert the regulatorymechanisms of enterocytes

Cytotoxins that destroy enterocytes Adherence to the muscosa by organisms

(enteroadherent organisms) that alterenterocytes functions as a result of physical

proximity to the mucosa

Invasion of mucosa by organisms thatprovoke an inflammatory response by theimmune system

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CLASSIFICATION OF DIARRHEA:

CHRONIC DIARRHEA

lasting for more than 4 weeks

Watery (Osmotic, Secretory), Inflammatory

and Fatty

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When poorly absorbable, lowmolecular weight aqueous solutes are

ingested, their osmotic force quickly

pulls water and, secondarily, ions intothe intestinal lumen

Maldigestion

Ingestion of a poorly absorbedsubstrate

Malabsorption

Watery Diarrhoea: Osmotic

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Osmotic diarrhea can also developwhen an ordinarily absorbable nutrient

is ingested by an individual with an

absorptive defect

Example, lactose by someone with

congenital lactase deficiency, orcarbohydrate by someone with gluten-

sensitive enteropathy (celiac disease)

Watery Diarrhoea: Osmotic

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Chronic Diarrhea : Inflammatory

diarrhea

Characterize by the presence of blood andpus in the stool which usually occurs as aresult of ulceration of the mucosa

Inflammatory bowel disease such asCrohns disease and ulcerative colitis

The lining of the gut becomes inflamed. Thisis usually caused by bacterial infections,viral infections, parasitic infections, orautoimmune problems such as IBS

(inflammatory bowel disease).

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Chronic Diarrhea: Fatty diarrhea

May result from malabsorption in mucosaldiseases

such as celiac disease whipple disease

short bowel syndrome secondary to extensivesurgical resection of small intestine

small bowl bacterial overgrowth syndrome

mesenteric ischemia

Also maybe the consequence of maldigestion offats cause by pancreatic exocrine deficiency or

inadequate luminal bile acid concentration

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INTERACTIONS OF THE ENTERIC

PATHOGEN WITH INTESTINAL MUCOSA

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Salmonella species produce diarrhea by

invading the lamina propria and setting up

an inflammatory process in the intestine.

S. typhi orgamisms proceed to invade thesystematic circulation.

Stools of patients with salmonellosis are

generally loose and watery, sometimescontaining blood and mucus.

Enterovasion with penetration of Lamina

Propria

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Adherence without enterotoxin

production nor no damage to the

enterocyte

Enteropathogenic E. Coli [EPEC]

After adhering to the surface of theenterocyte. The organism do not alaborate

toxins. They invade the mucosal epithelium

However some degree of disruption of the

microvilli and blunting of the intestinal villi has

been detected.

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Symptoms of diarrhea can be broken down

into uncomplicated and complicated diarrhea

Symptoms of uncomplicated diarrhea include:

Abdominal bloating or cramps

Thin or loose stools

Watery stool Sense of urgency to have a bowel movement

Nausea and vomiting

In addition to the symptoms described above, thesymptoms of complicated diarrhea include:

Blood, mucus, or undigested food in the stool

Weight loss (dehydration)

Fever

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Laboratory Tests

BASILLO, Rhealyn

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Laboratory Tests

O&P (Ova and Parasite) testing

Fecal WBC

Stool or fecal fat

Stool Culture

Enzyme-linked immunosorbent assay(ELISA)/Antigen testsforgiardia, cryptosporidium & E. histolytica.These tests detect protein structures on the parasites

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Food Allergy and intolerance tests

Celiac disease tests

Antibody tests for parasites. These are not asuseful to detect current infections but may be orderedto check for past or chronic infections, especially ifunusual parasitic infections are suspected

Electrolytes

Biopsy of the small intestines (rare)

Laboratory Tests

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Non-Laboratory Tests

colonoscopy with biopsy

sigmoidoscopy

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Differential diagnosis

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Malabsorption is the inability to absorb food,

mostly in the small bowel but also due tothe pancreas

Causes include:

enzyme deficiencies or mucosal abnormality,as in food allergy and food intolerance,(e.g. celiac disease (glutenintolerance), lactose intolerance (intolerance tomilk sugar, common in non-Europeans), fructose malabsorption)

loss of pancreatic secretions (may be dueto cystic fibrosis orpancreatitis)

Malabsorption

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Inflammatory bowel disease

Ulcerative colitis is marked by chronic

bloody diarrhea and inflammation mostlyaffects the distal colon near the rectum.

Crohn's disease typically affects fairly welldemarcated segments of bowel in the colon

and often affects the end of the small bowel.

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Other causes Diarrhea can be caused by

chronic ethanol ingestion

Ischemic bowel disease. This usually affects olderpeople and can be due to blocked arteries

Hormone-secreting tumors: some hormones(e.g., serotonin) can cause diarrhea if excreted inexcess (usually from a tumor)

Chronic mild diarrhea in infants and toddlers mayoccur with no obvious cause and with no other illeffects; this condition is called toddler's diarrhea.

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Classification, Diagnosis and Management of Chronic Diarrheal

Disorders *modified from Greenberger N.J.Kansas Medical Society

CAUSE EXAMPLES KEY ELEMENTS IN DIAGNOSIS TREATMENT

Iatrogenic dietary

factors

Excess tea,coffee,cola bevereges Careful history taking Appropriate dietary

modificationsInfectious enteritis Amebiasis Demonstrate leukocytes in stool Metronidazole diodoquin

antibiotics

Inflammatory boweldisease

Ulcerative colitis Hx:diarrhea,abdominal pain,rectal bleeding

Sulfasalazinecorticosteroids

Lactose intolerance Milk tolerance Milk abdominal pain,diarrhea,gas bloating

Discontinue milk

Laxative abuse Add few drops of NaOH to stool:bec. Most laxatives containphenolphthalein, stool will

turn red

Discontinue Laxatives

Drug induced Antacids,antibiotic (Clindamycin,lincomycin, ampicillin,

Penicillin, colchicines, lactulose,sorbitol

Careful hx taking and review ofmedication

D/c offending drug

Metabolic Diabetes mellitusHyperthyroidism

Adrenal insufficiency

Abnormal blood glucose level,T4, plasma cortisol,

response to synthetic ACTH

Appropriate to theunderlying disorder

Mechanical Fecal impaction Rectal examination Remove impaction

Neoplastic Carcinoma of the pancreasGastrinoma

Tumors producing VIP (Vasoactive intestinal

peptide)

Suspect the diagnosis Surgical

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Prevention and treatment

Key measures to prevent diarrhoea include:

access to safe drinking-water

improved sanitation

exclusive breastfeeding for the first six months of

life

good personal and food hygiene

health education about how infections spread rotavirus vaccination

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TREATMENT

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TREATMENT: Key measures to treat

diarrhoea include the following.Oral rehydration therapy (ORT)

is a simple treatment for dehydration associated

with diarrhea, particularly gastroenteritis orgastroenteropathy, such as that caused

by cholera or rotavirus

ORT consists of a solution of salts and sugars

which is taken by mouth

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Glucose is actively absorbed by

the normal small bowel and that

sodium carried with it about anequimolar ratio

During acute diarrhea absorptionof sodium without glucose is

impaired.

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Home Made ORT

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ORS

1liter 1 glass

1 level teaspoon of salt, tsp. Salt / 1 pinch

8 level teaspoons of

sugar, and2tsp. Sugar

1 liter of clean water 1 glass of water

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ORESOL POCKET: Concentrations of ingredients in reduced

osmolarity ORS

Ingredient g/L Molecule/ion mmol/L

sodium chloride (NaCl) 2.6 sodium 75

glucose, anhydrous (C6H12O6) 13.5 glucose 75

potassium chloride (KCl) 1.5 potassium 20

chloride 65

trisodium citrate, dihydrate

Na3C6H5O72H2O 2.9 citrate 10

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Limitations of ORT:ORT may prove ineffective

in the following circumstances

In pt. With very severe watery diarrhealosinggreater than 10ml/kg/hr, who may be unable todrink enough fluid to replace the continuinglosses.

In pt. With severe dehydration often with signs ofshock.

In pt. Who cannot drink because etremefatigue,stupor, or coma

In pt. With severe or sustained vomiting (more

than 5x/hr) In pt. With glucose and galactose intolerance.

In pt. With abfdominal distention

In the ORS solution has been incorrectly prepared,

or is incorrectly administered.

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Advantages of Breastfeeding Proper quality and quantity of nutrients

Anti-infective properties of breast milk are universallyeffective

Protect against gastrointestinal and respiratory infections

Major immunologic components:

IgA-over 90% of Ig in milk

IgG,IgE,IgM,IgD-10% Leukocytes

Other non-specific protective factors:

Lactoferrin

Lysozyme Complements system

Prevents hypersensitivity or allergy

Psychological advantages

Enhanced cognitive development

Convenient,always available

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MedicationsAntibiotics

Metronidazole

Anti motility agents

loperamide.

Bismuth compounds

(Pepto-Bismol) decreased the number of bowelmovements

Codeine phosphate

Codeine phosphate is used in the treatment ofdiarrhea to slow down Peristalsis and the passage offecal material through the bowels

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Enkephalinase inhibitor,

racecedotril

(also known as acetorphan)

has been shown to lessen the volume of

acute infectious diarrhea in children,

presumably by preventing breakdown of

enkephalins in the mucosa, which are anti-

secretory

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Zinc supplements

zinc supplements reduce the duration of adiarrhoea episode by 25% and are associated

with a 30% reduction in stool volume

A Cochrane systematic review found that zincsupplementation benefits children suffering from

diarrhea in developing countries, but only ininfants over six months old.

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Alternative therapies

A 2010 systematic review determined theeffectiveness of probiotics in treatingdiarrhoea. The study demonstrated that theuse of probiotics reduced the duration of

symptoms by one day and reduced thechances of symptoms lasting longer than fourdays by 60%. The probioticlactobacillus canhelp prevent antibiotic associated diarrhea in

adults but possibly not in children. For thosewho with lactose intolerance, takingdigestive enzymes containing lactase whenconsuming dairy products is recommended.

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1. Give extra fluid (as much as the child will take)

2. Give Zinc supplements

3. Continue feeding (exclusive breastfeeding if age

is less than 6 months)

4. When to return

PLAN A (4 rules in home treatment)

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a. Tell the mother

b. Teach the mother how to mix and give ORS

c. Show the mother how much fluid to give inaddition to the usual fluid intake

PLAN A (Four rules in home treatment)

1. Give extra fluid (as much as the child will take)

a Tell the mother

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a. Tell the mother

Breastfed frequently and for longer at each feed

If the child is exclusively breastfed, give ORS or clean

water in addition to breast milk If the child is not exclusively breastfed, five one or moreof the following: food-based fluids (soup, rice water,yoghurt drinks) and ORS

If the child vomits, wait for 10 minutes then continue

giving fluids but more slowly Continue giving extra fluid until the diarrhoea stops

b. Teach the mother how to mix and give ORS

c. Show the mother how much fluid to give in additionto the usual fluid intake

Up to two years: 50 100 ml after each loose stool

Two years or more: 100 200 ml after each loose stool

2 Give Zinc supplements

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2. Give Zinc supplements

Tell the mother how much zinc to give (20mg/tab)

2 months to 6 months: tab/day for 14 days

6 months and up: 1tab/day for 14 days

Show the mother how to give zinc supplements

Infants dissolve table in small amount of expressedbreast milk, ORS, or clan water in a cup

Older children tablets can be chewed or dissolved in

a small amount of clean water in a cup

3. Continue feeding (exclusive breastfeeding if ageis less than 6 months)

4. When to return

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PLAN B1.Determine amount of ORS to give during first 4

hours

2. Show the mother how to give ORS solution

3. After 4 hours

4. If the mother must leave before completingtreatment

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1. Determine amount of ORS to give during first 4 hours

Use the childs age only when you not know the weight.The approximate amount of ORS required (in ml) can

also be calculated by multiplying the childs weight in kgtimes 75

If the child wants more ORS than usual, give more

AGEUp to 4

months

4 months

12

months

12 months

2 years

2 years to 5

years

WEIGHT < 6 kg 6 10 kg 10 12 kg 12 20kg

Amount of

fluid

over

4hrs

200 450ml 450 800ml 800 960ml960

1600ml

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2. Show the mother how to give ORS solution

Give small frequent small sips from a cup

If the child vomits, wait for 10 minutes then continuegiving fluids but more slowly

Continue breastfeeding whenever the child wants

3. After 4 hours

Reassess the child and classify the child for dehydration Select appropriate plan to continue treatment

Begin feeding the child in clinic

4. If the mother must leave before completing treatment

Show her how to prepare ORS solution at home

Show her how much ORS to give to finish 4-hourtreatment at home

Explain the 4 rules of home treatment

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Sunken eyeballs

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CASE A

A mother brought her 10-month old, 8-kg daughterto a health center because of diarrhea of one-day

duration, which occurred 4 times. There was no

accompanying vomiting. She has been breastfed

since birth. At 5 months old, lugaw with fish and

vegetables were started, at the onset of diarrhea, the

stopped breastfeeding and the giving of solid foods

and instead shifted to giving am with sugar. The

child is alert, with good skin turgor and adequate

urine output.

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Chief Complaints: Diarrhea of one-day duration, which occurred 4 times. There was no accompanying vomiting

Assessment: Alert, with good skin turgor Adequate urine output

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CASE B

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CASE B

Benjie, a 3-year old weighing 11 kg, was brought to theemergency room because of diarrhea and vomiting of 3 days

duration. Diarrhea occurred 6 times a day and vomiting 3

times a day. Past history revealed that the patient was

breastfed for 2 months then shifted to Bonna, 1:2 dilution.

Solid food was started at 4 months old. The patient ispresently being given lugaw since the onset of diarrhea.

PE: patient was irritable, with temperature of 37C, cardiac

rate of 100/min, respiratory rate of 20/min, sunken eyeballs,mouth and tongue were dry, poor skin turgor, decreased

urine output. Abdomen as slightly distended with hypoactive

bowel sounds. Serum electrolytes showed normal sodium

and decreased potassium level.

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PE

patient was irritable

Remp 37CCR 100/min

RR 20/min

sunken eyeballs

mouth and tongue were dry

poor skin turgordecreased urine output

Abdomen as slightly distended with hypoactive bowel

sounds

LAB:

Serum electrolytes showed normal sodium

decreased potassium level.

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