Tropical sprue pathophysiology

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

Pathophysiology

Pathogenesis

Pathogenesis of tropical sprue is unclear and multiple theories are proposed.The factors involved in the pathogenesis of tropical sprue include:

• The most accepted theory is the small intestinal bacterial overgrowth affecting the enterocyte brush border activity, duodenal morphology causing villous atrophy and lymphocytosis in the intestinal cells.
• Impaired host immune response results in prolonged inflammation of the small bowel affecting the enterocyte function.
• Reduced gut defense mechanisms resulting in increased bacterial over growth damages the enterocytes and crypt cells to cause intestinal villous atrophy. This causes chronic diarrhea.
• Bile acid deconjugation affects the enterohepatic circulation and cause steatorrhea.
• Vitamin B12 deficiency can occur if the ileum is involved and the megaloblastic change in the intestinal mucuosal epithelium results in the formation of dysfunctional epithelial cells.
• Slow mouth to ceacum transit due to intestinal stasis promotes small intestinal bacterial over growth and patients with tropical sprue have higher levels of enteroglucagon, peptide YY, and neurotensin which decrease the motility of intestine all these can predispose to the development of tropical sprue.
• Mucosal disaccharidase deficiency is also a potential cause as patients with tropical sprue have higher levels of urinary lactulose excretion suggesting a deficiency of lactase enzyme.
• Post infectious diarrhea theory is supported by the occurrence of the disease following an episode of acute gastroenteritis, occurrence of the disease in epidemics in rural areas with poor sanitation, susceptibility of visitors from developed countries to endemic regions and the frequency of small bowel bacterial overgrowth in patients with tropical sprue.

Genetics

People with HLA HLA haplotypes, especially the Aw-19 series are at higher risk of developing tropical sprue.

Microscopic Pathology

• Small bowel biospy reveals similar changes as gluten sensitive enteropathy.
• The features demonstrated on a duodenal biopsy include :
  • Incomplete villous blunting
  • Intra epithelial lymphocytosis
  • Eosinophilic infilteration of the mucosa