Malabsorption Workup

• Hematologic tests

  • A CBC count may reveal microcytic anemia due to iron deficiency or macrocytic anemia due to vitamin B-12 or folate malabsorption.
  • Serum iron, vitamin B-12, and folate concentrations may help establish a diagnosis.
  • Prothrombin time may be prolonged because of malabsorption of vitamin K, a fat-soluble vitamin.
• Electrolytes and chemistries

  • Malabsorption can involve electrolyte imbalances, such as hypokalemia, hypocalcemia, hypomagnesemia, and metabolic acidosis.
  • Protein malabsorption may cause hypoproteinemia and hypoalbuminemia.
  • Fat malabsorption can lead to low serum levels of triglycerides, cholesterol, and alpha- and beta-carotene.
  • Westergren sedimentation rate is elevated in Crohn disease and Whipple disease.
• Serology

  • No serologic tests are specific for malabsorption.
  • Serum antigliadin and antiendomysial antibodies can be used to help diagnose celiac sprue.
  • Serum IgA can be used to rule out IgA deficiency.
  • Determination of fecal elastase and chymotrypsin (2 proteases produced by the pancreas) can be used to try to distinguish between pancreatic causes and intestinal causes of malabsorption.

• Small bowel barium studies

  • An abnormal small bowel pattern obtained from barium studies of the upper gastrointestinal tract may reveal the nature of malabsorption.
  • The mucosa pattern associated with celiac disease often becomes obliterated or coarsened.
  • Flocculation of the barium occurs in the gut lumen.
  • Small bowel dilatation and diverticulosis are frequently identified in scleroderma.
  • Regional enteritis of the small intestine can lead to stricture, ulceration, and fistula formation.
  • Other anatomic abnormalities, such as surgical changes or enterocolonic fistula, also can be detected on x-ray films.
• CT scan of the abdomen: Performing this study may help detect evidence of chronic pancreatitis, such as pancreatic calcification or atrophy. Enlarged lymph nodes are seen in Whipple disease and lymphoma.
• Endoscopic retrograde cholangiopancreatogram (ERCP): This study helps document malabsorption due to pancreatic or biliary-related disorders.
• Plain abdominal x-ray film: Pancreatic calcifications are indicative of chronic pancreatitis.

• Tests of fat malabsorption

  • This usually is the first test because many disease processes result in fat malabsorption.
  • For a quantitative measurement of fat absorption, a 72-hour fecal fat collection is often performed and is considered the criterion standard.
  • Qualitative tests include the acid steatocrit test and Sudan III stain of stool, but these tests are less reliable.
  • Instruct patients to consume a normal amount (80-100 g/d) of fat before and during the collection. Based on this intake, fecal fat excretion in healthy individuals should be less than 7 g/d.
• D-xylose test

  • If the 72-hour fecal fat collection results demonstrate fat malabsorption, the D-xylose test is used to document the integrity of the intestinal mucosa.
  • Facilitated diffusion in the proximal intestine primarily absorbs D-xylose.
  • Approximately half of the absorbed D-xylose is excreted in urine, unmetabolized. If the absorption of D-xylose is impaired due to either a luminal factor (eg, bacterial overgrowth) or a reduced or damaged mucosal surface area (eg, surgical resection, celiac disease), urinary excretion is lower than normal.
  • Cases of pancreatic insufficiency usually result in normal urinary excretion because the absorption of D-xylose is still intact.
• Tests of carbohydrate absorption

  • A simple sensitive test for carbohydrate malabsorption is the hydrogen breath test, in which patients are given an oral solution of lactose.^{[9, 10]}
  • In cases of lactase deficiency, colonic flora digest the unabsorbed lactose, resulting in an elevated hydrogen content in the expired air.
  • Bacterial overgrowth or rapid transit also can cause an early rise in breath hydrogen, necessitating the use of glucose instead of lactose to make a diagnosis. However, 18% of patients are hydrogen nonexcretors, causing a false-negative test result.
• Test of bile salt absorption

  • The bile salt breath test can determine the integrity of bile salt metabolism.
  • The patient is given oral conjugated bile salt, such as glycine cholic acid with the glycine radiolabeled in the carbon position.
  • The bile salt is deconjugated and subsequently metabolized by bacteria, leading to a radioactively labeled elevated breath carbon dioxide level if interrupted enterohepatic circulation, such as bacterial overgrowth, ileal resection, or disease, is present.
• Schilling test

  • Malabsorption of vitamin B-12 may occur as a consequence of deficiency of intrinsic factor (eg, pernicious anemia, gastric resection), pancreatic insufficiency, bacterial overgrowth, ileal resection, or disease.
  • The 3-stage Schilling test results often can help differentiate these conditions.
• ¹³ C-D-xylose breath test

  • Hope et al suggest that small intestinal malabsorption in chronic alcoholism may be determined by a ¹³ C-D-xylose breath test.^[11] The investigators evaluated the¹³ C-D-xylose breath test in 14 alcoholics, compared the breath test results with those of untreated celiac patients and healthy controls, and correlated the breath test findings to morphologic findings of the duodenal mucosa.^[11] Hope et al found significantly reduced absorption of¹³ C-D-xylose in the alcoholic individuals relative to the healthy controls, whereas the time curve of¹³ C-D-xylose absorption in the alcoholics was similar in appearance to that of the untreated celiac patients. In addition, despite few light microscopic changes in the alcoholics, morphologic pathology, primarily a reduced surface area of microvilli, was observed under electron microscopy in the majority of the patients.^[11]

• Upper endoscopy with small bowel mucosal biopsy

  • Establishing a definitive diagnosis of malabsorption of the mucosal phase often can be achieved by histologic examination of biopsied mucosal specimens obtained during routine upper endoscopy.
  • Examples of conditions that can be diagnosed this way include celiac sprue, giardiasis, Crohn disease, Whipple disease, amyloidosis, abetalipoproteinemia, and lymphoma.

Depending on the cause, the histologic features of malabsorption vary. A frequently encountered histologic finding is villous atrophy, which is seen in celiac disease, tropical sprue, viral gastroenteritis, bacterial overgrowth, inflammatory bowel disease, immunodeficiency syndromes, lymphoma, and radiation enteritis.