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  • Celiac disease—characteristic though not specific small bowel mucosal lesion, positive anti–tissue transglutaminase test (anti-tTGA) or antiendomysial antibody test (anti-EMA), and clinical response to gluten withdrawal. HLA-DQ2 and/or HLA-DQ8 present in >99%.

  • Tropical sprue—appropriate geographic exposure; exclude other mucosal diseases (eg, celiac disease and protozoal infestation), exclude small intestinal bacterial overgrowth, and assess response to antibiotics and folate.

  • Eosinophilic gastroenteritis—histologic demonstration of increased gastric, intestinal, or colonic mucosal or mural eosinophilic infiltration or eosinophilic ascites.

  • Systemic mastocytosis—demonstration of increased mucosal mast cells (>20 per high-power field) in stomach, small bowel, colon; elevated serum tryptase.

  • Radiation enteritis—history of radiation with mucosal telangiectasias, obliterative endarteriolitis, fibrosis, and strictures; small intestinal bacterial overgrowth may develop.

  • Whipple disease—demonstrates Tropheryma whipplei and characteristic periodic acid–Schiff-positive macrophages in intestinal mucosa or other tissue.

  • Small intestinal bacterial overgrowth—document evidence of malabsorption, positive breath test (lactulose, glucose) or culture of jejunal aspirate if available, response to antibiotics.

  • Short bowel syndrome—history of small bowel resection and confirmation by imaging (barium contrast small bowel series or computed tomographic enterography).

  • Intestinal lymphangiectasia—hypoproteinemia, lymphopenia, evidence of protein-losing enteropathy, increased fecal loss of α1-antitrypsin.


Normally the human gastrointestinal tract digests and absorbs dietary nutrients with remarkable efficiency. A typical Western diet ingested by an adult includes approximately 100 g of fat, 400 g of carbohydrate, 100 g of protein, 2 L of fluid, and the required sodium, potassium, chloride, calcium, vitamins, and other elements. Salivary, gastric, intestinal, hepatic, and pancreatic secretions add an additional 7–8 L of protein-, lipid-, and electrolyte-containing fluid to intestinal contents. This massive load is reduced by the small and large intestines to less than 200 g of stool that contains less than 8 g of fat, 1–2 g of nitrogen, and less than 20 mM each of Na+, K+, Cl, HCO3, Ca2+, or Mg2+.

If there is impairment of any of the many steps involved in the complex process of nutrient digestion and absorption, intestinal malabsorption may ensue. If the abnormality involves a single step in the absorptive process, as in primary lactase deficiency, or if the disease process is limited to the very proximal small intestine, selective malabsorption of only a single nutrient (iron or folate) may occur. However, generalized malabsorption of multiple dietary nutrients develops when the disease process is extensive, thus disturbing several digestive and absorptive processes, as occurs in celiac disease with extensive involvement of the small intestine.


Many authors classify diseases associated with malabsorption into three major categories: (1) those associated with impaired intraluminal digestion; (2) those associated with impaired mucosal digestion and absorption; and (3) those associated with impaired postmucosal nutrient transport (Table 20–1). Indeed, these are the major mechanisms of intestinal absorption and some disease entities fit neatly into ...

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