Diarrhea

OUR LADY OF FATIMA UNIVERSITYFatima College of Medicine

Department of Biochemistry and Nutrition

BIOCHEMICAL ASPECTS OF DIARRHOEA

BARSAGA, Mark LesterBASILLO, RhealynBAUI, Bernard Jr.

BANAS, Philip GideonBELADA, Ralph Patrick

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

OBJECTIVESAfter 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.

• 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.

Key facts (WHO, August 2009)

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 classified

1,610 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

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 gastoenteritis of 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 pulmonary disease and allied conditions

174 164 338 4.43

10. Other protein-calorie malnutrition 175 159 334 4.38

Ten (10) Leading Causes of Child Mortality By Age-Group (5-9) & Sex No. & Rate/100,000 population, Philippines,

(Source: Philippine Health Statistics 2000, DOH)

Cause5-9 Years

Male Female Both Rate

1. Accidents 1,044 618 1,662 17.82

2. Pneumonia 368 288 656 7.03

3. Malignant Neoplasm 201 169 370 3.97

4. Congenital Anomalies 135 131 266 2.85

5. Diarrheas and gastroenteritis of presumed infectious origin

112 92 204 2.19

6. Other diseases of the nervous system

118 83 201 2.15

7. Meningitis 105 95 200 2.14

8. Diseases of the heart 99 75 174 1.87

9. Tuberculosis, all forms 83 62 145 1.55

10. Septicemia 79 53 132 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

• 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 gluten-sensitive enteropathy (celiac disease)

Watery Diarrhoea: Osmotic

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 Crohn’s 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

• 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.

Enterovasion with penetration of Lamina Propria

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

• 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)

Laboratory Tests

Non-Laboratory Tests

• colonoscopy  with biopsy

• sigmoidoscopy

Differential diagnosis

• 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 non-Europeans), fructose malabsorption)

• loss of pancreatic secretions (may be due to cystic fibrosis or pancreatitis)

Malabsorption

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 EXAMPLES KEY ELEMENTS IN DIAGNOSIS TREATMENT

Iatrogenic dietary factors

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

Infectious enteritis Amebiasis Demonstrate leukocytes in stool Metronidazole diodoquin antibiotics

Inflammatory bowel disease

Ulcerative colitis Hx:diarrhea,abdominal pain, rectal bleeding

Sulfasalazine corticosteroids

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

Discontinue milk

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

turn red

Discontinue Laxatives

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

Penicillin, colchicines, lactulose, sorbitol

Careful hx taking and review of medication

D/c offending drug

Metabolic Diabetes mellitusHyperthyroidism

Adrenal insufficiency

Abnormal blood glucose level, ↑T4, ↓plasma cortisol, ↓

response to synthetic ACTH

Appropriate to the underlying disorder

Mechanical Fecal impaction Rectal examination Remove impaction

Neoplastic Carcinoma of the pancreasGastrinoma

Tumors producing VIP (Vasoactive intestinal peptide)

Suspect the diagnosis 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 glass

1 level teaspoon of salt, ¼ tsp. Salt / 1 pinch

8 level teaspoons of sugar, and

2tsp. Sugar

1 liter of clean water 1 glass of water

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 Na3C6H5O7·2H2O

2.9 citrate 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

MedicationsAntibiotics• 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 anti-secretory

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.

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)

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

PLAN A (Four rules in home treatment)

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

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: ½ 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 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 completing treatment

1. Determine amount of ORS to give during first 4 hours– Use the child’s age only when you not know the weight.

The approximate amount of ORS required (in ml) can also be calculated by multiplying the child’s weight in kg times 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

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 AA 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.

PEpatient was irritableRemp – 37C CR – 100/minRR – 20/minsunken eyeballsmouth and tongue were drypoor skin turgordecreased urine outputAbdomen as slightly distended with hypoactive bowel sounds

LAB:Serum electrolytes showed normal sodiumdecreased potassium level.