Chronic diarrhea pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omodamola Aje B.Sc, M.D. [2]

The fundamental pathophysiology of all diarrhea is incomplete absorption of water from the lumen because of either a reduced rate of net water absorption or osmotic retention of water intraluminally. The causes of chronic diarrhea include inflammatory, osmotic, secretory, iatrogenic, motility, and functional diseases. Osmotic chronic diarrhea involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients. If excessive amounts of unabsorbed substance are retained in the intestinal lumen, water will not be absorbed and diarrhea will result. Secretory chronic diarrhea on the other hand, results from disordered electrolyte transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion. A disruption of the normal colonic epithelial barrier by microorganisms is mainly responsible for inflammatory chronic diarrhea. This disruption can lead to exudative, secretory, or malabsorptive components of inflammatory chronic diarrhea. Both rapid transit time and slow transit time are associated with motility disorders causing chronic diarrhea. Some iatrogenic causes of chronic diarrhea are seen after abdominal surgeries such as cholecystectomy, where about 5%–10% of patients develop chronic diarrhea. In general, the causes of chronic diarrhea are multifactorial.

Diarrhea is a condition of altered intestinal water and electrolyte transport. The physiological mechanisms of diarrhea include osmotic, secretory, inflammatory, altered motility, and iatrogenic mechanisms.^[1]

Osmotic chronic diarrhea involves an unabsorbed substance that draws water from the plasma into the intestinal lumen along osmotic gradients. If excessive amounts of unabsorbed substance are retained in the intestinal lumen, water will not be absorbed and diarrhea will result.

• Chronic diarrhea due to an osmotic cause includes osmotic laxatives such as lactose intolerance antacids, fructose, lactulose, laxatives magnesium, phosphate, and sorbitol.^[2]
• Maldigestion syndromes such as disaccharidase deficiency and pancreatic exocrine insufficiency can also result in osmotic chronic diarrhea.
• Osmotic diarrheas might result in steatorrhea and azotorrhea (passage of fat and nitrogenous substances into the stool), but they typically do not cause any rectal bleeding.^[3]

Secretory chronic diarrhea results from disordered electrolyte transport and, despite the term, is more commonly caused by decreased absorption rather than net secretion.

• Secretory diarrheas include congenital abnormalities such as congenital chloridorrhea, in which an abnormality in the genetic control of chloride-bicarbonate exchange in the ileum results in the loss of chloride into the stool.
• Another example is the loss of α2-adrenergic function in enterocytes of patients with autonomic neuropathy caused by diabetes mellitus.
• The typical features of secretory diarrhea include the persistence of the diarrhea with fasting and the absence of steatorrhea, azotorrhea, or blood per rectum.
• Secretory diarrheas caused by neuroendocrine tumors have been identified by measurement of plasma levels of the hormone or its metabolite in the urine.
• Investigations include measurements of VIP, gastrin, or calcitonin in plasma or 24-hour collections of urine for 5-hydroxyindoleacetic acid.^[4]

Disruption of the normal colonic epithelial barrier by microorganisms is mainly responsible for inflammatory chronic diarrhea. This disruption can lead to exudative, secretory, or malabsorptive components of inflammatory chronic diarrhea.

• Inflammatory causes of chronic diarrhea might present with features that suggest malabsorption or rectal bleeding.
• The nature of the malabsorption depends on the regions affected (e.g., proximal vs. distal small bowel), and rectal bleeding is usually a manifestation of colonic or rectal ulcerations.
• Anti-inflammatory agents, including bismuth subsalicylate or other, more potent anti-inflammatory medications, appear to benefit patients with microscopic or collagenous colitis.^[5]

Both rapid transit time and slow transit time are associated with motility disorders causing chronic diarrhea.

• Rapid transit time delivers fluid secreted during digestion to the distal small bowel or colon. This prevents reabsorption of normally secreted fluid in the small bowel, overwhelming the re-absorptive capacity of the colon.
• Slow transit time results in bacterial overgrowth with bile acid deconjugation, poor micelle formation, and steatorrhea.
• The clinical manifestations of chronic diarrhea caused by motility disorders include steatorrhea, usually up to 14 g per day.
• Osmotic laxatives result in acceleration of transit through the bowel, which is associated with up to 14 g of fat in the stool.
• Presence of more than 14 g per day of fat in the stool suggests the presence of bacterial overgrowth or associated disease such as celiac disease.^[6]

After abdominal surgeries such as cholecystectomy, about 5%–10% of patients develop chronic diarrhea.

• Most of these cases resolve completely or significantly improve within a couple of months.
• Iatrogenic diarrhea is related to excessive bile acids being delivered into the intestine.^[7][8]
• After a cholecystectomy, bile is delivered directly into the small bowel, overcoming the terminal ileum‘s ability to reabsorb adequately, leading to cholerheic diarrhea.
• Some other iatrogenic causes of chronic diarrhea might result from vagal injury and ileal resection.

For the details of the genetics, associated conditions, gross and microscopic pathology of the following causes of chronic diarrhea, click the links below.

• Ulcerative colitis
• Crohn’s disease
• Lactose intolerance
• Celiac disease
• Chronic pancreatitis
• Cholera
• Microsporidiosis
• Giardiasis
• Cryptosporidiosis
• Hyperthyroidism

Template:WH Template:WS