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1 suwandi sadikin 130110110009 B1 case 4B GIS

Diarrhea (mechanism of major diarrhea)

Diarrhea is an increase in the frequency of defecation and the fluidity, volume, and weight of feces and is
often a protective response. Three or more stools per day are considered abnormal. Many factors determine stool
volume and consistency, including water content of the colon and the presence of unabsorbed food, unabsorbable
material, and intestinal secretions. Stool volume in the normal adult averages less than 200 g/day. Stool volume in
children depends on age and size. An infant may pass up to 100 g/day.
PATHOPHYSIOLOGY
Diarrhea in which the volume of feces is increased is called large-volume diarrhea. Large volume diarrhea
generally is caused by excessive amounts of water or secretions or both in the intestines. Small-volume diarrhea, in
which the volume of feces is not increased, usually results from excessive intestinal motility. The three major
mechanisms of diarrhea are osmotic, secretory, and motility.
1.

In osmotic diarrhea a nonabsorbable substance in the intestine draws water into the lumen by osmosis. The
excess water and the nonabsorbable substance cause large-volume diarrhea.
Magnesium, sulfate, and phosphate are poorly absorbed ions and can increase intraluminal osmotic
pressure.
Lactase deficiency is the most common cause of osmotic diarrhea
Loss of pancreatic enzymes can be a contributing factor.
In this condition the nonabsorbable substance is milk sugar, or lactose. Lactose remains in the intestinal lumen
because it is not digested or absorbed . Excessive ingestion of synthetic, nonabsorbable sugars (e.g., sorbitol) has a
similar effect. Osmotic diarrhea disappears when ingestion of the osmotic substance stops. Malabsorption related to
bile salt deficiency, small intestine bacterial overgrowth, and celiac disease also cause diarrhea. Osmotic diarrhea
stops with fasting, has a low pH, and is positive for reducing substances
TABLE 338-1 -- Causes of Osmotic Diarrhea
MALABSORPTION OF WATER-SOLUBLE NUTRIENTS
Glucose-galactose malabsorption
Congenital
Acquired
Disaccharidase deficiencies (lactase and sucrase-isomaltase)
Congenital
Acquired
EXCESSIVE INTAKE OF CARBONATED FLUIDS
EXCESSIVE INTAKE OF NONABSORBABLE SOLUTES
Sorbitol
Lactulose
Magnesium hydroxide

2.

Secretory diarrhea is a form of large-volume diarrhea caused by excessive mucosal secretion of chloride- or
bicarbonate- rich fluid or inhibition of net sodium absorption. The mechanisms for secretory diarrhea include
activation of the intracellular mediators such as cAMP, cGMP, and intracellular calcium, which stimulate active
chloride secretion from the crypt cells and inhibit the neutral coupled sodium chloride absorption. These
mediators alter the paracellular ion flux because of toxin-mediated injury to the tight junctions.
The classic example of secretory diarrhea is that induced by cholera and Escherichia coli enterotoxins
that bind to a specific enterocyte surface receptor (the monosialoganglioside GM 1); a fragment of the toxin
then enters the cell, where it activates adenylate cyclase on the basolateral membrane via interaction with a
stimulatory G protein. This increases intracellular cAMP. The enterotoxigenic E. coli mediates secretory diarrhea
by producing heat-labile toxin (LT) and heat-stable toxin (ST) in the small bowel. The labile toxin is similar in its
action to the cholera toxin and binds to the same GM1 surface receptor. Younger patients are more predisposed
to the effects of ST because the number of ST receptors is higher during early life compared to that in adults.
Other causes of secretory diarrhea include vasoactive peptides, which activate G proteincoupled receptors,
resulting in an increase in intracellular mediators causing secretory diarrhea.

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2 suwandi sadikin 130110110009 B1 case 4B GIS
Secretory diarrhea is characterized by high volume; the stools are extremely watery. Stool analysis reveals high
sodium and chloride content (>70 mEq/L). Secretory diarrhea continues with fasting.

TABLE 338-3 -- Causes of Secretory Diarrhea

ACTIVATION OF CYCLIC ADENOSINE MONOPHOSPHATE
Bacterial toxins: enterotoxins of cholera, Escherichia coli (heat-labile), Shigella, Salmonella, Campylobacter
jejuni, Pseudomonas aeruginosa
Hormones:vasoactive intestinal peptide, gastrin, secretin
Anion surfactants: bile acids, ricinoleic acid
ACTIVATION OF CYCLIC GUANOSINE MONOPHOSPHATE
Bacterial toxins: E. coli (heat-stable) enterotoxin, Yersinia enterocolitica toxin
CALCIUM-DEPENDENT
Bacterial toxins: Clostridium difficile enterotoxin
Neurotransmitters:acetylcholine, serotonin
Paracrine agents:bradykinin
TABLE 338-2 -- Differential Diagnosis of Osmotic Vs Secretory Diarrhea
OSMOTIC DIARRHEA

SECRETORY DIARRHEA

Volume of stool

<200 mL/24 hr

>200 mL/24 hr

Response to fasting

Diarrhea stops

Diarrhea continues

<70 mEq/L

>70 mEq/L

Positive

Negative

<5

>6

Stool Na+
Reducing substances
Stool pH
*

[*]

Sucrose is not a reducing agent. Add 5 drops of 0.1 N HCl to a stool sample before adding reducing agent (Clinitest
tablet).
3.

Alteration in Intestinal Motility.

The causes of altered intestinal motility include malnutrition, scleroderma, intestinal pseudo-obstruction
syndromes, and diabetes mellitus. Malnutrition, in general, results in hypomotility, allowing bacterial
overgrowth that leads to deconjugation of bile salts, resulting in an increase in the intracellular mediator cAMP
and leading to secretory diarrhea.

4.

Mutational Defects in Ion Transport Proteins.

Congenital defects of sodium-hydrogen exchange, chloride-bicarbonate exchange, and sodiumbile
acid transport proteins result in secretory diarrhea presenting at birth. The defects in chloride-bicarbonate
exchange and sodiumbile acid transporters have gene mutations that encode their corresponding transport
proteins. The defect in sodium-hydrogen exchange is believed to represent defects in the apical sodiumhydrogen exchangers. Patients with these defects present with secretory diarrhea and failure to thrive during
the neonatal period. The defect in chloride-bicarbonate exchange is well characterized, and is more common
compared with the defects in sodium-hydrogen exchange and sodiumbile acid transporter. Patients with
chloride diarrhea have hypochloremic metabolic alkalosis with low serum chloride concentration, high stool
chloride content coupled with chloride-free urine, low serum potassium, and high serum bicarbonate.
Hydramnios is present in the mothers

5.

Reduction in Anatomic Surface Area.

Short bowel syndrome results from resection of the bowel secondary to surgical indications such as
necrotizing enterocolitis, midgut volvulus, or intestinal atresia. Celiac disease results in flattening of the
proximal intestinal surface area with marked decrease in the digestive and absorptive function of the villus
epithelium. Diarrhea is characterized by loss of fluids, electrolytes, macronutrients, and micronutrients.

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3 suwandi sadikin 130110110009 B1 case 4B GIS
Reference : Nelson Pediatric 18th edition and Mosby Pathophysiology the Basis of Disease for Adult and Children.