PATHOPHYSIOLOGY OF DIARRHEA

Azilah Sulaiman

Measured stool volume greater than 10ml/kg/day, including changed consistency of stool (loose or watery) and frequency (≥3 episodes within 24H)

Acute diarrhea: < 2/52 Persistent diarrhea: 2-3/52 Chronic diarrhea: > 4/52

Frequent passing of formed stools in not considered as diarrhea

DefinitionDefinition

Practical pediatric, 5th edition, Churchill & Livington, 2003

Pocket guide on management of acute diarrhea 2011

Mechanisms of DiarrheaMechanisms of Diarrhea

6 mechanisms explain pathophysiology of diarrhea

More than 1 mechanism may present at the same time

Fluid and Electrolyte Balance in GIT

Main osmotic substances:

Na+, Cl-, HCO3-

Main osmotic substances:

Na+, Cl-, HCO3-

Primary Mechanis

m

Defect Stool Examinati

on

Examples Comment

Secretory Secretory Absorption Secretion & electrolytes transport

WateryNormal osmolality

Cholera, E.coli, carcinoid, VIP, neuroblastoma, Clostridium difficile, cryptosporidiosis (AIDS)

Persist during fasting; bile salt malabsorption may intestinal water secretion; no stool leukocytes

Osmotic Osmotic Maldigestion, transport defect, ingestion of unabsorbable solute

Watery, acidic, and reducing substances; increased osmolality

Lactase deficiency, glucose-galactose malabsorption, lactulose, laxative abuse

Stops with fasting, increased breath hydrogen with carbohydrate malabsorption; no stool leukocytes

Primary Mechanis

m

Defect Stool Examination

Examples Comment

DecreaseDecreased motilityd motility

Defect in neuromuscular unit (s)

Stasis (bacterial overgrowth)

Loose to normal appearing stool

PseudoobstructionBlind loops

Possible bacterial overgrowth

Increased Increased motilitymotility

Decreased transit time

Loose to normal appearing stool, stimulated by gastrocolic reflex

IBS, thyrotoxicosis, postvagotomy dumping syndrome

Infection may also contribute to increased motility

Primary Mechanis

m

Defect Stool Examinati

on

Examples Comment

DecreaseDecreased surface d surface

area area (osmotic, (osmotic, motility)motility)

Decreased functional capacity

Watery Short bowel syndrome, celiac disease, rotavirus enteritis

May require elemental diet plus parenteral alimentation

Mucosal Mucosal invasioninvasion

Inflammation, decreased colonic reabsorption, increased motility

Blood and increased WBC in stool

Salmonella, Shigella, Yersinia,amebiasis Campylobacter,

Dysentery = blood + mucus + WBCs

Nelson textbook of pediatrics, 16th edition

Major Causes of Diarrheal Major Causes of Diarrheal IllnessesIllnesses

Major Causes of Diarrheal Illnesses:

Secretory Diarrhea

Infectious:1.Rotavirus2.Caliciviruses3.Enteric adenoviruses4.Astroviruses

Infectious: endotoxin mediated1.Vibrio cholera2.Escherichia coli 3.Bacillus cereus4.Clostridium perfringens

Neoplastic:1. Tumor elaboration of

peptide, serotonin or prostaglandins

2. Villous adenoma in distal colon (nonhormone mediated)

Excess in laxative usage

Osmotic Diarrhea

1. Disaccharides (lactase) deficiency2. Lactulose therapy (for hepatic encephalopathy, constipation)3. Perscribed gut lavage for diagnostic procedures4. Antacids (MgSO4 and other magnesium salts)5. Primary bile acids malabsorption

Major Causes of Diarrheal Illnesses:

Exudative Diseases

Infectious: bacterial damage to mucosal epithelium1. Shigella 2. Salmonella3. Campylobacter4. Entamoeba hystolytica

Idiopathic inflammatory bowel disease

Malabsorption

1. Defective intraluminal digestion2. Primary mucosal cell abnormalities3. Reduced small intestine surface area4. Lymphatic obstruction5. Infectious: Giardia lamblia infection

Major Causes of Diarrheal Illnesses:

Deranged Motility

Decreased intestinal transit time1. Surgical reduction of gut length2. Neural dysfunction – IBS3. Hyperthyroidism4. Diabetic neuropathy5. Carcinoid syndrome

Decreased motility (increased intestinal transit time)1. Small intestine diverticula2. Surgical creation of ‘blind’ intestinal loops3. Bacterial overgrowth in small intestine

Evaluation of DiarrheaEvaluation of Diarrhea

Acute vs. chronic diarrhea Acute diarrhea

Complete history/physical examination Stool examination for occult blood and WBC

Negative + no hx to suggest contaminated food viral

Positive bacterial causes must be excluded 1st Absence of bacterial pathogens & toxins

inflammatory bowel disease (esp. in adolescent with weight loss, fever & abdominal pain)

Stool for parasites: not helpful unless diarrhea persists

Differential Diagnosis of Diarrhea

Infant Child Adolescent

ACUTE-CommoCommon n

-Rare Rare

1.Gastroenteritis2.Systemic infection3.Antibiotic associated4.Overfeeding

1.Primary disaccharides defiency2.Hirshsprung toxic colitis3.Adrenogenital sydrome

1.Gastroenteritis2.Food poisoning3.Systemic infection4.Antibiotic associated

1.Toxic ingestion

1.Gastroenteritis2.Food poisoning3.Antibiotic associated

1.hyperthyroidism

Differential Diagnosis of Diarrhea

Infant Child Adolescent

CHRONIC -Common

-Rare

1.Postinfectious secondary lactase deficiency 2.Cow’s milk/ soy protein intolerance3.Chronic nonspecific diarrhea in infancy (toddler’s diarrhea)4.Celiac disease5.Cystic fibrosis6.AIDS enteropathy

1.Primary immune defects2.Familial villous atrophy3.Secretory tumors4.Congential chloridorrhea5.Acrodermatitis enteropathica6.Lymphagiectasia7.Eosinophilic gastroenteritis8.Short bowel syndrome9.Autoimmune enteropathy

1.Postinfectious secondary lactase deficiency 2.Irritable bowel syndrome3.Celiac disease4.Lactose intolerance 5.Giardiasis6.AIDS enteropathy

1.Acquired immune defects2.Secretory tumors3.Pseudoobstruction4.Factitious

1. Irritable bowel syndrome

2. Inflammatory bowel disease

3. Lactose intolerance4. Giardiasis5. Laxative abuse

(anorexia nervosa)6. AIDS enteropathy

1. Secretory tumors2. Primary bowel

tumor3. Gay bowel disease

Nelson textbook of pediatrics, 16th edition

Specific Causes of Infectious Diarrhea:

VIRAL CAUSES: Rotavirus:Rotavirus:

Mostly during winter months Primary infection in infancy – moderate to

severe illness Reinfection in adolescent – mild illness MOA:

invade upper small intestine May extend throughout small intestine and colon –

villous damage, secondary transient disaccharide deficiency & inflammation of lamina propria

Vomiting: 3-4days, diarrhea: 7-10days

Vomiting: 3-4days, diarrhea: 7-10days Treatment: supportive

Addition of probiotic (lactobacillus GG) or enkephalinase inhibitor (racecadotril) may shorten duration of illness

Refractory cases- protracted diarrhea may benefit from oral IgG or lactobacillus GG

Organisms Virulence properties

Campylobacter jejuni Invasion, enterotoxin

Clostridium difficile Cytotoxin, enterotoxin

Cyclospora Inflammation

Escherichia Coli

-Enteropathogenic (EPEC)

-Enterotoxigenic (ETEC)

-Enteroinvasive (EIEC)

-Enterohemorrhagic (EHEC) –

[O157:H7]

-Enteroadherent (EAEC)

-adherence, effacement

-Enterotoxin (heat stable or

labile)

-Invasion

-Adherence, effacement,

cytotoxin – HUS

-Adherence, mucosal damage

Organisms Virulence properties

Shigella Invasion, enterotoxin, cytotoxin

Salmonella Invasion, enterotoxin

Vibrio cholerae Enterotoxin

Yersinia enterocolitica Invasion, enterotoxin

Giardia lamblia Cyst resistant to physical destruction; adherence to mucosa

Cryptosporidium adherence

Entamoeba histolytica Cyst resistant to physical destruction; invasion; enzyme and cytotoxin production

Oral Rehydration Therapy:

The cheapest way to treat diarrhea – to prevent dehydration

Adequate glucose-electrolyte solution WHO recommendation: ORT + guidance

on appropriate feeding practices main strategy to achieve reduction in diarrhea related morbidity and mortality

ORAL REHYDRATION SALT: non proprietary name for a balanced glucose-electrolyte mixture

19691969: ORS 1st introduced 19841984:

Mixture containing trisodium citrate instead of hydrogen carbonate was introduced

Aim: to produce stability of ORS in hot and humid climate

Original ORS: Contain 90mEq/L of sodiumContain 90mEq/L of sodium total total

osmolarity of 311mOsm/Losmolarity of 311mOsm/L

Feb2004Feb2004: WHO/UNICEF improved ORS formula to “reduced osmolarity “reduced osmolarity ORS”ORS”

Why reduced osmolarity ORS?

Pharmacokinetics and therapeutics values Glucose facilitates absorption of sodium (hence

water) on 1:1 molar basis in small intestine Sodium & potassium are needed to replace

body loss in diarrhea Citrate corrects acidosis that may occur as

results of diarrhea and dehydration**Citrate: systemic alkalizing agent & is used as buffer, sequestrant &

emulsion stabilizer, freely soluble in water

Other clinical benefits: Reduces stool output or stool volume by

~25% - when compared to original WHO-UNICEF ORS solution

Reduces vomiting by ~30% Reduces need for unscheduled IV therapy

>30% Less hospitalization