Congenital lactase deficiency is an autosomal recessive disorder caused by mutations in the gene encoding lactase. The disease is rare and manifests as explosive diarrhea with watery, frothy stools and abdominal distention after milk ingestion. Symptoms abate when exposure to milk and milk products is terminated.
Acquired lactase deficiency is caused by downregulation of lactase gene expression and is particularly common among Native Americans, African Americans, and Chinese populations. Downregulation of lactase occurs in the gut after childhood, perhaps reflecting the fact that, before farming of dairy animals, lactase was unnecessary after children stopped drinking mother’s milk. Onset of acquired lactase deficiency is sometimes associated with enteric viral or bacterial infections.
Abetalipoproteinemia is an autosomal recessive disease characterized by an inability to secrete triglyceride-rich lipoproteins. Although rare, it is an example of a trans-epithelial transport defect leading to malabsorption. Mutation in the microsomal triglyceride transfer protein renders enterocytes unable to export lipoproteins and free fatty acids. As a result, monoglycerides and triglycerides accumulate within the epithelial cells. Abetalipoproteinemia manifests in infancy, and the clinical picture is dominated by failure to thrive, diarrhea, and steatorrhea. Failure to absorb essential fatty acids leads to deficiencies of fat-soluble vitamins, and lipid defects in plasma membranes often produce acanthocytic red blood cells (spur cells) in peripheral blood smears.
Microscopic colitis encompasses two entities, collagenous colitis and lymphocytic colitis. Both of these idiopathic diseases manifest with chronic, nonbloody, watery diarrhea without weight loss. Findings on radiologic and endoscopic studies typically are normal. Collagenous colitis, which occurs primarily in middle-aged and older women, is characterized by the presence of a dense subepithelial collagen layer, increased numbers of intraepithelial lymphocytes, and a mixed inflammatory infiltrate within the lamina propria. Lymphocytic colitis is histologically similar, but the subepithelial collagen layer is of normal thickness and the increase in intraepithelial, predominantly T lymphocytes, may be greater. Lymphocytic colitis is associated with celiac disease and autoimmune diseases, including thyroiditis, arthritis, and autoimmune or lymphocytic gastritis.
Graft-versus-host disease occurs after allogeneic hematopoietic stem cell transplantation. The small bowel and colon are involved in most cases. Although graft-versus-host disease is caused by donor T cell–mediated damage to the recipient’s epithelial cells, the lymphocytic infiltrate in the lamina propria is typically sparse, suggesting that cytokines secreted by T cells may be the major mediators of tissue injury. Epithelial apoptosis, particularly of crypt cells, is the most common histologic finding. Intestinal graft-versushost disease often manifests as watery diarrhea.
Diarrheacanbecharacterizedassecretory, osmotic, malabsorptive, orexudative.
Themalabsorptionassociatedwithcysticfibrosisistheresultofpancreatic insufficiency (i.e.,inadequatepancreaticdigestiveenzymes)anddeficient luminal breakdown ofnutrients.
Celiac disease isanimmune-mediatedenteropathytriggeredbytheingestionofgluten-containinggrains.Themalabsorptivediarrheainceliacdiseaseisduetoloss of brush border surface area and,possibly,deficiententerocytematuration.
Lactase deficiency causesanosmotic diarrhea owingtotheinabilitytobreakdownorabsorblactose.