PATHOPHYSIOLOGY
OF DIARRHEA
Azilah Sulaiman
Definition






Measured stool volume greater than 10ml/kg/day,
including changed consistency of stool (loose or
wate...
Mechanisms of Diarrhea




6 mechanisms explain pathophysiology of
diarrhea
More than 1 mechanism may present at the
sam...
Fluid and Electrolyte Balance in
GIT
Main osmotic
Main osmotic
substances:
substances:
Na+,+,Cl-,-,HCO3-3Na Cl HCO
Primary
Mechanism

Defect

Secretory

 Absorption
 Secretion &
electrolytes
transport

Osmotic

Maldigestion,
transport
...
Primary
Mechanism

Defect

Decreased
motility

Defect in
neuromuscula
r unit (s)

Stool
Examination

Examples

Comment

Lo...
Primary
Mechanism

Defect

Decreased Decreased
surface area functional
(osmotic, capacity
motility)

Mucosal
invasion

Inf...
Major Causes of Diarrheal
Illnesses
Major Causes of Diarrheal Illnesses:
Secretory Infectious:
Diarrhea 1.Rotavirus
2.Cali...
Major Causes of Diarrheal Illnesses:
Exudative
Diseases

Infectious: bacterial damage to mucosal epithelium
1. Shigella
2....
Major Causes of Diarrheal Illnesses:
Deranged
Motility

Decreased intestinal transit time
1. Surgical reduction of gut len...
Evaluation of Diarrhea



Acute vs. chronic diarrhea
Acute diarrhea



Complete history/physical examination
Stool exa...
Differential Diagnosis of Diarrhea
Infant
ACUTE
-Common

-Rare

Child

Adolescent

1.Gastroenteritis
2.Systemic infection
...
Differential Diagnosis of Diarrhea
Infant
CHRONIC
-Common

-Rare

Child

Adolescent

1.Postinfectious secondary
lactase de...
Specific Causes of Infectious
Diarrhea:
VIRAL CAUSES:
 Rotavirus:






Mostly during winter months
Primary infection...



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

of probiotic (lactobacillus GG) or enkephalin...
Organisms

Virulence properties

Cam
pylobacter jejuni

Invasion, enterotoxin

Clostridium difficile

Cytotoxin, enterotox...
Organisms

Virulence properties

S
higella

Invasion, enterotoxin, cytotoxin

S onella
alm

Invasion, enterotoxin

Vibrio ...
Oral Rehydration Therapy:







The cheapest way to treat diarrhea – to
prevent dehydration
Adequate glucose-electrol...



1969: ORS 1st introduced
1969
1984:
1984






Mixture containing trisodium citrate instead of
hydrogen carbonate ...


Feb2004: WHO/UNICEF  improved ORS
Feb2004
formula to “reduced osmolarity ORS”
Why reduced osmolarity ORS?


Pharmacokinetics and therapeutics values






Glucose facilitates absorption of sodium ...


Other clinical benefits:





Reduces stool output or stool volume by ~25% when compared to original WHO-UNICEF ORS
...
Pathophysiology of diarrhea
Pathophysiology of diarrhea
Pathophysiology of diarrhea
Pathophysiology of diarrhea
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Pathophysiology of diarrhea

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Pathophysiology of diarrhea

  1. 1. PATHOPHYSIOLOGY OF DIARRHEA Azilah Sulaiman
  2. 2. Definition     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 Practical pediatric, 5th edition, Churchill & Livington, 2003 Fre q ue nt p a s s ing o f fo rm e d s to o ls in no t c o ns id e re d a s d ia rrhe a Pocket guide on management of acute diarrhea 2011
  3. 3. Mechanisms of Diarrhea   6 mechanisms explain pathophysiology of diarrhea More than 1 mechanism may present at the same time
  4. 4. Fluid and Electrolyte Balance in GIT
  5. 5. Main osmotic Main osmotic substances: substances: Na+,+,Cl-,-,HCO3-3Na Cl HCO
  6. 6. Primary Mechanism Defect Secretory  Absorption  Secretion & electrolytes transport Osmotic Maldigestion, transport defect, ingestion of unabsorbable solute Stool Examination Examples Comment Watery Normal osmolality Cholera, E.coli, carcinoid, VIP, neuroblastoma, Clostridium difficile, cryptosporidiosis (AIDS) Persist during fasting; bile salt malabsorption may intestinal water secretion; no stool leukocytes 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
  7. 7. Primary Mechanism Defect Decreased motility Defect in neuromuscula r unit (s) Stool Examination Examples Comment Loose to normal Pseudoobstructio appearing stool n Blind loops Possible bacterial overgrowth Loose to normal appearing stool, stimulated by gastrocolic reflex Infection may also contribute to increased motility Stasis (bacterial overgrowth) Increased motility Decreased transit time IBS, thyrotoxicosis, postvagotomy dumping syndrome
  8. 8. Primary Mechanism Defect Decreased Decreased surface area functional (osmotic, capacity motility) Mucosal invasion Inflammation, decreased colonic reabsorption, increased motility Stool Examination Watery Examples Comment Short bowel syndrome, celiac disease, rotavirus enteritis May require elemental diet plus parenteral alimentation Blood and Salmonella, Dysentery = blood increased Shigella, + mucus + WBCs WBC in stool Yersinia,amebiasi s Campylobacter, Nelson textbook of pediatrics, 16th edition
  9. 9. Major Causes of Diarrheal Illnesses Major Causes of Diarrheal Illnesses: Secretory Infectious: Diarrhea 1.Rotavirus 2.Caliciviruses 3.Enteric adenoviruses 4.Astroviruses Infectious: endotoxin mediated 1.Vibrio cholera 2.Escherichia coli 3.Bacillus cereus 4.Clostridium perfringens Osmotic Diarrhea 1. 2. 3. 4. 5. Neoplastic: 1. Tumor elaboration of peptide, serotonin or prostaglandins 2. Villous adenoma in distal colon (nonhormone mediated) Excess in laxative usage Disaccharides (lactase) deficiency Lactulose therapy (for hepatic encephalopathy, constipation) Perscribed gut lavage for diagnostic procedures Antacids (MgSO4 and other magnesium salts) Primary bile acids malabsorption
  10. 10. Major Causes of Diarrheal Illnesses: Exudative Diseases Infectious: bacterial damage to mucosal epithelium 1. Shigella 2. Salmonella 3. Campylobacter 4. Entamoeba hystolytica Idiopathic inflammatory bowel disease Malabsorption 1. 2. 3. 4. 5. Defective intraluminal digestion Primary mucosal cell abnormalities Reduced small intestine surface area Lymphatic obstruction Infectious: Giardia lamblia infection
  11. 11. Major Causes of Diarrheal Illnesses: Deranged Motility Decreased intestinal transit time 1. Surgical reduction of gut length 2. Neural dysfunction – IBS 3. Hyperthyroidism 4. Diabetic neuropathy 5. Carcinoid syndrome Decreased motility (increased intestinal transit time) 1. Small intestine diverticula 2. Surgical creation of ‘blind’ intestinal loops 3. Bacterial overgrowth in small intestine
  12. 12. Evaluation of Diarrhea   Acute vs. chronic diarrhea Acute diarrhea   Complete history/physical examination Stool examination for occult blood and W BC + no hx to suggest contaminated food  viral  Positive  bacterial causes must be excluded 1st  Negative   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
  13. 13. Differential Diagnosis of Diarrhea Infant ACUTE -Common -Rare Child Adolescent 1.Gastroenteritis 2.Systemic infection 3.Antibiotic associated 4.Overfeeding 1.Gastroenteritis 2.Food poisoning 3.Systemic infection 4.Antibiotic associated 1.Gastroenteritis 2.Food poisoning 3.Antibiotic associated 1.Primary disaccharides defiency 2.Hirshsprung toxic colitis 3.Adrenogenital sydrome 1.Toxic ingestion 1.hyperthyroidism
  14. 14. Differential Diagnosis of Diarrhea Infant CHRONIC -Common -Rare Child Adolescent 1.Postinfectious secondary lactase deficiency 2.Cow’s milk/ soy protein intolerance 3.Chronic nonspecific diarrhea in infancy (toddler’s diarrhea) 4.Celiac disease 5.Cystic fibrosis 6.AIDS enteropathy 1.Postinfectious secondary lactase deficiency 2.Irritable bowel syndrome 3.Celiac disease 4.Lactose intolerance 5.Giardiasis 6.AIDS enteropathy 1. Irritable bowel syndrome 2. Inflammatory bowel disease 3. Lactose intolerance 4. Giardiasis 5. Laxative abuse (anorexia nervosa) 6. AIDS enteropathy 1.Primary immune defects 2.Familial villous atrophy 3.Secretory tumors 4.Congential chloridorrhea 5.Acrodermatitis enteropathica 6.Lymphagiectasia 7.Eosinophilic gastroenteritis 8.Short bowel syndrome 9.Autoimmune enteropathy 1.Acquired immune defects 2.Secretory tumors 3.Pseudoobstruction 4.Factitious 1. Secretory tumors 2. Primary bowel tumor 3. Gay bowel disease Nelson textbook of pediatrics, 16th edition
  15. 15. Specific Causes of Infectious Diarrhea: VIRAL CAUSES:  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
  16. 16.   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
  17. 17. Organisms Virulence properties Cam pylobacter jejuni Invasion, enterotoxin Clostridium difficile Cytotoxin, enterotoxin Cyclospora Inflammation E scherichia Coli -Enteropathogenic (EPEC) -adherence, effacement -Enterotoxigenic (ETEC) -Enterotoxin (heat stable or labile) -Enteroinvasive (EIEC) -Invasion -Enterohemorrhagic (EHEC) – -Adherence, effacement, cytotoxin – [O157:H7] HUS -Enteroadherent (EAEC) -Adherence, mucosal damage
  18. 18. Organisms Virulence properties S higella Invasion, enterotoxin, cytotoxin S onella alm Invasion, enterotoxin Vibrio cholerae Enterotoxin Yersinia enterocolitica Invasion, enterotoxin Giardia lam blia Cyst resistant to physical destruction; adherence to mucosa Cryptosporidium adherence E ntam oeba histolytica Cyst resistant to physical destruction; invasion; enzyme and cytotoxin production
  19. 19. 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
  20. 20.   1969: ORS 1st introduced 1969 1984: 1984    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/ of sodium total osmolarity L of 311mOsm/ L
  21. 21.  Feb2004: WHO/UNICEF  improved ORS Feb2004 formula to “reduced osmolarity ORS”
  22. 22. 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
  23. 23.  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

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