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The Schilling test is performed to determine the cause of cobalamin malabsorption. Unfortunately, this test has not been available commercially in the United States for the last few years. Since an understanding of the physiology and pathophysiology of cobalamin absorption is very valuable in enhancing one’s understanding of aspects of gastric, pancreatic, and ileal function, discussion of the Schilling test is provided as supplemental information to Chap. 349. Because cobalamin absorption requires multiple steps, including gastric, pancreatic, and ileal processes, the Schilling test also can be used to assess the integrity of the organs involved in those processes (Chap. 128).

Cobalamin is present primarily in meat. Except in strict vegans, dietary cobalamin deficiency is exceedingly uncommon. Dietary cobalamin is bound in the stomach to a glycoprotein called R-binder protein, which is synthesized in both the stomach and the salivary glands. This cobalamin–R binder complex is formed in the acid milieu of the stomach. Cobalamin absorption has an absolute requirement for intrinsic factor, another glycoprotein synthesized and released by gastric parietal cells, to promote its uptake by specific cobalamin receptors on the brush border of ileal enterocytes. Pancreatic protease enzymes split the cobalamin–R binder complex to release cobalamin in the proximal small intestine, where cobalamin then is bound by intrinsic factor.

As a consequence, cobalamin absorption may be abnormal in the following conditions:

  1. Pernicious anemia. In this disease, immunologically mediated atrophy of gastric parietal cells leads to an absence of both gastric acid and intrinsic factor secretion.

  2. Chronic pancreatitis can result from a deficiency of pancreatic proteases to split the cobalamin–R binder complex. Although 50% of patients with chronic pancreatitis reportedly have an abnormal Schilling test that is corrected by pancreatic enzyme replacement, cobalamin-responsive macrocytic anemia in chronic pancreatitis is extremely rare. Although this probably reflects a difference in the digestion/absorption of cobalamin in food versus that in a crystalline form, the Schilling test still can be used to assess pancreatic exocrine function.

  3. Achlorhydria is the absence of hydrochloric acid; intrinsic factor is also secreted with acid which is responsible for splitting cobalamin away from the proteins in food to which it is bound. Up to one-third of individuals >60 years of age have marginal vitamin B12 absorption because of an inability to release cobalamin from food; these people have no defects in the absorption of crystalline vitamin B12.

  4. Bacterial overgrowth syndromes, which are most often secondary to stasis in the small intestine, lead to bacterial utilization of cobalamin (often referred to as stagnant bowel syndrome; see below).

  5. Ileal dysfunction (as a result of either inflammation or prior intestinal resection) is due to impaired function of the mechanism of cobalamin–intrinsic factor uptake by ileal intestinal epithelial cells.

In the Schilling test, 58Co-labeled cobalamin is administered orally, and urine is collected for 24 h. The test is dependent ...

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