Pathophysiology of diarrhea

1. PATHOPHYSIOLOGY
OF DIARRHEA
Azilah Sulaiman

2. 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, 5
th
edition, Churchill & Livington, 2003
Pocket guide on management of acute diarrhea 2011

3. Mechanisms of DiarrheaMechanisms of Diarrhea
6 mechanisms explain pathophysiology of
diarrhea
More than 1 mechanism may present at the
same time

5. Fluid and Electrolyte Balance in
GIT

7. '
5'6
7
8
&9
:
&9
.
: Main osmotic
substances:
Na
+
, Cl
-
, HCO
3
-

8. Primary
Mechanism
Defect Stool
Examination
Examples Comment
Secretory Secretory  Absorption
 Secretion &
electrolytes
transport
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
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

10. Primary
Mechanism
Defect Stool
Examination
Examples Comment
Decreased Decreased
motilitymotility
Defect in
neuromuscula
r unit (s)
Stasis
(bacterial
overgrowth)
Loose to normal
appearing stool
Pseudoobstructio
n
Blind 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

11. Primary
Mechanism
Defect Stool
Examination
Examples Comment
Decreased Decreased
surface area surface 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,amebiasi
s Campylobacter,
Dysentery = blood
+ mucus + WBCs
Nelson textbook of pediatrics, 16
th
edition

12. Major Causes of Diarrheal Major Causes of Diarrheal
IllnessesIllnesses
Major Causes of Diarrheal Illnesses:
Secretory
Diarrhea
Infectious:
1.Rotavirus
2.Caliciviruses
3.Enteric adenoviruses
4.Astroviruses
Infectious: endotoxin mediated
1.Vibrio cholera
2.Escherichia coli
3.Bacillus cereus
4.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) deficiency
2.Lactulose therapy (for hepatic encephalopathy, constipation)
3.Perscribed gut lavage for diagnostic procedures
4.Antacids (MgSO
4
and other magnesium salts)
5.Primary bile acids malabsorption

13. 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
Malabsorption1.Defective intraluminal digestion
2.Primary mucosal cell abnormalities
3.Reduced small intestine surface area
4.Lymphatic obstruction
5.Infectious: Giardia lamblia infection

14. 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

15. 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 1
st

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

16. Differential Diagnosis of Diarrhea
Infant Child Adolescent
ACUTE
-Common Common
-Rare Rare
1.Gastroenteritis
2.Systemic infection
3.Antibiotic associated
4.Overfeeding
1.Primary disaccharides
defiency
2.Hirshsprung toxic colitis
3.Adrenogenital sydrome
1.Gastroenteritis
2.Food poisoning
3.Systemic infection
4.Antibiotic associated
1.Toxic ingestion
1.Gastroenteritis
2.Food poisoning
3.Antibiotic
associated
1.hyperthyroidism

17. Differential Diagnosis of Diarrhea
Infant Child Adolescent
CHRONIC
-Common
-Rare
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.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.Postinfectious secondary
lactase deficiency
2.Irritable bowel syndrome
3.Celiac disease
4.Lactose intolerance
5.Giardiasis
6.AIDS enteropathy
1.Acquired immune
defects
2.Secretory tumors
3.Pseudoobstruction
4.Factitious
1.Irritable bowel
syndrome
2.Inflammatory bowel
disease
3.Lactose intolerance
4.Giardiasis
5.Laxative abuse
(anorexia nervosa)
6.AIDS enteropathy
1.Secretory tumors
2.Primary bowel tumor
3.Gay bowel disease
Nelson textbook of pediatrics, 16
th
edition

19. 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

20. 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

21. 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

22. 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

23. 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

24. 
19691969: ORS 1
st
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 osmolarity total osmolarity
of 311mOsm/Lof 311mOsm/L

25. 
Feb2004Feb2004: WHO/UNICEF  improved ORS
formula to “reduced osmolarity ORS”“reduced osmolarity ORS”

26. 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

27. 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