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 Patrick
Section A2, Group 1 Second Semester S.Y. 2010 2011

OBJECTIVES
After the discussion, the students will be able to know 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 of diarrhea

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 variety of bacterial, viral and parasitic organisms.

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.

Key facts (WHO, August 2009)

Diarrhoeal disease is the second leading cause of death in 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 two years old. Diarrhoea is a leading cause of malnutrition in children under five years old.

INFANT MORTALITY: TEN (10) LEADING CAUSES NUMBER AND RATE/per 1000 live births AND PERCENTAGE DISTRIBUTION, Philippines, 2005 (DOH)
Cause 1. Bacterial sepsis of newborn 2. Respiratory distress of newborn 3. Pneumonia 4. Disorders related to short gestation and low birth weight, not elsewhere classified 5. Congenital Pneumonia 6. Congenital malformation of the heart 7. Neonatal aspiration syndrome 8. Other congenital malformation 9. Intrauterine hypoxia and birth asphyxia 10.Diarrhea and gastro-enterities of presumed infectious origin Number 3,161 2,298 2,013 1,610 1,510 1,444 1,146 1,012 971 900 Rate 1.9 1.4 1.2 1 0.9 0.9 0.7 0.6 0.6 0.5 Percent 14.6 10.6 9.3 7.4 7 6.7 5.3 4.7 4.5 4.2

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)

Cause 1. Pneumonia 2. Accidents 3. Diarrheas and gastoenteritis of presumed infectious origin 4. Measles 5. Congenital anomalies 6. Malignant Neoplasm 7. Meningitis 8. Septicemia 9. Chronic obstructive pulmonary disease and allied conditions 10. Other protein-calorie malnutrition

1-4 Years Male 1,540 839 685 452 350 219 201 173 174 175 Female 1,341 506 546 425 337 153 155 173 164 159 Both 2,881 1,345 Rate 37.76 17.63

1,231 16.14 877 687 372 356 346 338 334 11.50 9.01 4.88 4.67 4.54 4.43 4.38

Ten (10) Leading Causes of Child Mortality By Age-Group (59) & Sex No. & Rate/100,000 population, Philippines,
(Source: Philippine Health Statistics 2000, DOH)
Cause 1. Accidents 2. Pneumonia 3. Malignant Neoplasm 4. Congenital Anomalies 5. Diarrheas and gastroenteritis of presumed infectious origin 6. Other diseases of the nervous system 7. Meningitis 8. Diseases of the heart 9. Tuberculosis, all forms 10. Septicemia 5-9 Years Male 1,044 368 201 135 112 118 105 99 83 79 Female 618 288 169 131 92 83 95 75 62 53 Both 1,662 656 370 266 204 201 200 174 145 132 Rate 17.82 7.03 3.97 2.85 2.19 2.15 2.14 1.87 1.55 1.41

CLASSIFICATION OF DIARRHEA

BANAS, Philip Gideon

CLASSIFICATION OF DIARRHEA
1. Acute Diarrhea 2. Chronic Diarrhea a. Watery i. Osmotic ii. Secretory b. Inflammatory c. Fatty

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 entamoeba histolytica) Consumption of potentially contaminated food and drinks is another risk factor for infectious diarrhea

Pathogenic infections cause diarrhea by one or four mechanisms

Enterotoxins that subvert the regulatory mechanisms of enterocytes Cytotoxins that destroy enterocytes Adherence to the muscosa by organisms (enteroadherent organisms) that alter enterocytes functions as a result of physical proximity to the mucosa Invasion of mucosa by organisms that provoke an inflammatory response by the immune system

CLASSIFICATION OF DIARRHEA: CHRONIC DIARRHEA

lasting for more than 4 weeks Watery (Osmotic, Secretory), Inflammatory and Fatty

Watery Diarrhoea: Osmotic

When poorly absorbable, low molecular weight aqueous solutes are ingested, their osmotic force quickly pulls water and, secondarily, ions into the intestinal lumen Maldigestion Ingestion of a poorly absorbed substrate Malabsorption

Watery Diarrhoea: Osmotic

Osmotic diarrhea can also develop when an ordinarily absorbable nutrient is ingested by an individual with an absorptive defect Example, lactose by someone with congenital lactase deficiency, or carbohydrate by someone with glutensensitive enteropathy (celiac disease)

Chronic Diarrhea : Inflammatory diarrhea

Characterize by the presence of blood and pus in the stool which usually occurs as a result of ulceration of the mucosa Inflammatory bowel disease such as Crohns disease and ulcerative colitis The lining of the gut becomes inflamed. This is usually caused by bacterial infections, viral infections, parasitic infections, or autoimmune problems such as IBS (inflammatory bowel disease).

Chronic Diarrhea: Fatty diarrhea

May result from malabsorption in mucosal diseases such as celiac disease whipple disease short bowel syndrome secondary to extensive surgical resection of small intestine small bowl bacterial overgrowth syndrome mesenteric ischemia Also maybe the consequence of maldigestion of fats cause by pancreatic exocrine deficiency or inadequate luminal bile acid concentration

INTERACTIONS OF THE ENTERIC PATHOGEN WITH INTESTINAL MUCOSA

Enterovasion with penetration of Lamina Propria

Salmonella species produce diarrhea by invading the lamina propria and setting up an inflammatory process in the intestine. S. typhi orgamisms proceed to invade the systematic circulation. Stools of patients with salmonellosis are generally loose and watery, sometimes containing blood and mucus.

Adherence without enterotoxin production nor no damage to the enterocyte

Enteropathogenic E. Coli [EPEC] After adhering to the surface of the enterocyte. 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.

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, the symptoms of complicated diarrhea include: Blood, mucus, or undigested food in the stool Weight loss (dehydration) Fever

Laboratory Tests

BASILLO, Rhealyn

Laboratory Tests
O&P (Ova and Parasite) testing Fecal WBC Stool or fecal fat Stool Culture Enzyme-linked immunosorbent assay (ELISA)/Antigen tests for giardia, cryptosporidium & E. histolytica. These tests detect protein structures on the parasites

Laboratory Tests
Food Allergy and intolerance tests Celiac disease tests Antibody tests for parasites. These are not as useful to detect current infections but may be ordered to check for past or chronic infections, especially if unusual parasitic infections are suspected Electrolytes Biopsy of the small intestines (rare)

Non-Laboratory Tests
colonoscopy with biopsy sigmoidoscopy

Differential diagnosis

Malabsorption
Malabsorption is the inability to absorb food, mostly in the small bowel but also due to the pancreas Causes include: enzyme deficiencies or mucosal abnormality, as in food allergy and food intolerance, (e.g. celiac disease (gluten intolerance), lactose intolerance (intolerance to milk sugar, common in nonEuropeans), fructose malabsorption) loss of pancreatic secretions (may be due to cystic fibrosis or pancreatitis)

Inflammatory bowel disease

Ulcerative colitis is marked by chronic bloody diarrhea and inflammation mostly affects the distal colon near the rectum. Crohn's disease typically affects fairly well demarcated segments of bowel in the colon and often affects the end of the small bowel.

Other causes
Diarrhea can be caused by chronic ethanol ingestion Ischemic bowel disease. This usually affects older people and can be due to blocked arteries Hormone-secreting tumors: some hormones (e.g., serotonin) can cause diarrhea if excreted in excess (usually from a tumor) Chronic mild diarrhea in infants and toddlers may occur with no obvious cause and with no other ill effects; this condition is called toddler's diarrhea.

Classification, Diagnosis and Management of Chronic Diarrheal Disorders *modified from Greenberger N.J.Kansas Medical Society
CAUSE Iatrogenic dietary factors Infectious enteritis Inflammatory bowel disease Lactose intolerance Laxative abuse EXAMPLES Excess tea,coffee,cola bevereges Amebiasis Ulcerative colitis Milk tolerance KEY ELEMENTS IN DIAGNOSIS Careful history taking Demonstrate leukocytes in stool Hx:diarrhea,abdominal pain, rectal bleeding Milk abdominal pain, diarrhea,gas bloating Add few drops of NaOH to stool: bec. Most laxatives contain phenolphthalein, stool will turn red Antacids,antibiotic (Clindamycin, lincomycin, ampicillin, Penicillin, colchicines, lactulose, sorbitol Diabetes mellitus Hyperthyroidism Adrenal insufficiency Fecal impaction Carcinoma of the pancreas Gastrinoma Tumors producing VIP (Vasoactive intestinal peptide) Careful hx taking and review of medication TREATMENT Appropriate dietary modifications Metronidazole diodoquin antibiotics Sulfasalazine corticosteroids Discontinue milk Discontinue Laxatives

Drug induced

D/c offending drug

Metabolic

Abnormal blood glucose level, T4, plasma cortisol, response to synthetic ACTH Rectal examination Suspect the diagnosis

Appropriate to the underlying disorder

Mechanical Neoplastic

Remove impaction Surgical

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

TREATMENT

TREATMENT: Key measures to treat diarrhoea include the following.

Oral rehydration therapy (ORT) is a simple treatment for dehydration associated with diarrhea, particularly gastroenteritis or gastroenteropathy, such as that caused by cholera or rotavirus ORT consists of a solution of salts and sugars which is taken by mouth

 Glucose is actively absorbed by the normal small bowel and that sodium carried with it about an equimolar ratio During acute diarrhea absorption of sodium without glucose is impaired.

Home Made ORT

ORS
1liter 1 level teaspoon of salt, 8 level teaspoons of sugar, and 1 liter of clean water 1 glass tsp. Salt / 1 pinch 2tsp. Sugar 1 glass of water

ORESOL POCKET: Concentrations of ingredients in reduced osmolarity ORS Ingredient sodium chloride (NaCl) glucose, anhydrous (C6H12O6) potassium chloride (KCl) g/L 2.6 13.5 1.5 Molecule/ion mmol/L sodium glucose potassium chloride trisodium citrate, dihydrate Na3C6H5O72H2O 2.9 citrate 75 75 20 65 10

Limitations of ORT:ORT may prove ineffective in the following circumstances

In pt. With very severe watery diarrhealosing greater than 10ml/kg/hr, who may be unable to drink enough fluid to replace the continuing losses. In pt. With severe dehydration often with signs of shock. In pt. Who cannot drink because etreme fatigue,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.

Advantages of Breastfeeding
Proper quality and quantity of nutrients Anti-infective properties of breast milk are universally effective 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

Medications
Antibiotics Metronidazole Anti motility agents loperamide. Bismuth compounds (Pepto-Bismol) decreased the number of bowel movements Codeine phosphate Codeine phosphate is used in the treatment of diarrhea to slow down Peristalsis and the passage of fecal material through the bowels

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 antisecretory

Zinc supplements
zinc supplements reduce the duration of a diarrhoea episode by 25% and are associated with a 30% reduction in stool volume A Cochrane systematic review found that zinc supplementation benefits children suffering from diarrhea in developing countries, but only in infants over six months old.

Alternative therapies
A 2010 systematic review determined the effectiveness of probiotics in treating diarrhoea. The study demonstrated that the use of probiotics reduced the duration of symptoms by one day and reduced the chances of symptoms lasting longer than four days by 60%. The probioticlactobacillus can help prevent antibiotic associated diarrhea in adults but possibly not in children. For those who with lactose intolerance, taking digestive enzymes containing lactase when consuming dairy products is recommended.

PLAN A (4 rules in home treatment)

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 (Four rules in home treatment) 1. Give extra fluid (as much as the child will take)

a. Tell the mother b. Teach the mother how to mix and give ORS c. Show the mother how much fluid to give in addition to the usual fluid intake

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 more of 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 addition to 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 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 expressed breast 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 age is less than 6 months) 4. When to return

PLAN B
1. 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 completing treatment

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 kg times 75 If the child wants more ORS than usual, give more Up to 4 months < 6 kg 4 months 12 months 6 10 kg 12 months 2 years to 5 2 years years 10 12 kg 12 20kg 960 1600ml

AGE WEIGHT Amount of fluid over 4hrs

200 450ml

450 800ml 800 960ml

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 continue giving 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-hour treatment at home Explain the 4 rules of home treatment

Sunken eyeballs

CASE A
A mother brought her 10-month old, 8-kg daughter to 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.

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

CASE B
Benjie, a 3-year old weighing 11 kg, was brought to the emergency 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 is presently 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.

PE patient was irritable Remp 37C CR 100/min RR 20/min sunken eyeballs mouth and tongue were dry poor skin turgor decreased urine output Abdomen as slightly distended with hypoactive bowel sounds LAB: Serum electrolytes showed normal sodium decreased potassium level.