gastrointestinal disorders
Overview of Malabsorption
Diagnosis of Malabsorption
Diagnosis typically clinically apparent from a detailed patient history Blood tests to screen for consequences of malabsorption Stool fat testing to confirm malabsorption (if unclear) Cause diagnosed with endoscopy, contrast x-rays, or other tests based on findings Malabsorption is suspected in a patient with chronic diarrhea, weight loss, and anemia. The etiology is sometimes obvious. For example, patients with malabsorption due to Chronic Pancreatitis usually have had prior bouts of acute pancreatitis. Patients with If the history suggests a specific cause, testing should be directed to that condition (see figure). If no cause is readily apparent, blood tests can be used as screening tools (eg, complete blood count, red blood cell indices, ferritin, vitamin B12, folate, calcium,albumin, cholesterol, prothrombin time). Test results may suggest a diagnosis and direct further investigation. Megaloblastic Macrocytic Anemias should prompt measurement of serum folate and B12 levels. Folate deficiency is common in mucosal disorders involving the proximal small bowel (eg, Microcytic anemia suggests iron deficiency, which may occur with celiac disease.Albuminis a general indicator of nutritional state. Lowalbumincan result from poor intake, decreased synthesis in cirrhosis, or protein wasting. Low serum carotene (a precursor ofvitamin A) suggests malabsorption if intake is adequate. Tests to confirm malabsorption are appropriate when symptoms are vague and the etiology is not apparent. Most tests for malabsorption assess fat malabsorption because it is relatively easy to measure. Confirmation of carbohydrate malabsorption is not helpful once steatorrhea is documented. Tests for protein malabsorption are rarely used because fecal nitrogen is difficult to measure. Direct measurement of fecal fatfrom a 72-hour stool collection is the gold standard test for establishing steatorrhea but unnecessary with gross steatorrhea of obvious cause. However, this test is available routinely in only a few centers. Stool is collected for a 3-day period during which the patient consumes≥100 g fat/day. Total fat in the stool is measured. Fecal fat>7 g/day is abnormal. Although severe fat malabsorption (fecal fat≥40 g/day) suggests pancreatic insufficiency or small-bowel mucosal disease, this test cannot determine the specific cause of malabsorption. Some test results include a fractional fat excretion that is defined as the average grams of stool fat excreted per day divided by the average grams of fat consumed per day. A fractional fat excretion of > 7% indicates fat malabsorption. Because the test is messy, unpleasant, and time consuming, it is unacceptable to most patients and difficult to do. Sudan III staining of a stool smearis a simple and direct, but nonquantitative, screening test for fecal fat. Acid steatocrit is a gravimetric assay done on a single stool sample; it has a reported high sensitivity and specificity (using 72-hour collection as the standard). Near-infrared reflectance analysis (NIRA) simultaneously tests stool for fat, nitrogen, and carbohydrates. These tests are not widely available in the United States. Measurement of elastase and chymotrypsinin the stool can also help differentiate pancreatic and intestinal causes of malabsorption; both are decreased in pancreatic exocrine insufficiency, whereas both are normal in intestinal causes. TheD-xylose absorption testcan be done if the etiology is not obvious; however, it is currently rarely used because of the advent of advanced endoscopic and imaging tests. Although it can noninvasively assess intestinal mucosal integrity and help differentiate mucosal from pancreatic disease, an abnormal D-xylose test result requires an endoscopic examination with biopsies of the small-bowel mucosa. As a result, small-bowel biopsy has replaced this test to establish intestinal mucosal disease. D-xylose is absorbed by passive diffusion and does not require pancreatic enzymes for digestion. A normal D-xylose test result in the presence of moderate to severe steatorrhea indicates pancreatic exocrine insufficiency rather than small-bowel mucosal disease. SIBO can cause abnormal results because the enteric bacteria metabolize pentose, thus decreasing the D-xylose available for absorption. After fasting, the patient is given 25 g of D-xylose in 200 to 300 mL of water orally. Urine is collected over 5 hours, and a venous sample is obtained after 1 hour. Serum D-xylose<20 mg/dL (1.33 mmol/L) or<4 g in the urine sample indicates abnormal absorption. Falsely low levels can also occur in renal diseases, portal hypertension, ascites, or delayed gastric emptying time. More specific diagnostic tests (eg, upper endoscopy, colonoscopy, barium x-rays) are indicated to diagnose several causes of malabsorption. Upper endoscopywith small-bowel biopsy is done when mucosal disease of the small bowel is suspected or if the D-xylose test result is abnormal in a patient with massive steatorrhea. Endoscopy allows visual assessment of small-bowel mucosa and helps direct biopsies to affected areas. Aspirate from the small bowel can be sent for bacterial culture and colony count to document bacterial overgrowth if there is clinical suspicion. Video Capsule Endoscopy can be used to look for diseases of the distal small intestine that are beyond the reach of a regular endoscope. Histologic features on small-bowel biopsy (see table) can establish the specific mucosal disease. Disorder Disorder Histologic Characteristics Histologic Characteristics Normal Fingerlike villi with a villous:crypt ratio of about 4:1 Columnar epithelial cells with numerous regular microvilli (brush border) Mild round cell infiltration in the lamina propria Celiac Disease (untreated) Virtual absence of villi and elongated crypts Increased intraepithelial lymphocytes and round cells (especially plasma cells) in the lamina propria Cuboidal epithelial cells with scanty, irregular microvilli Intestinal Lymphangiectasia None Dilation and ectasia of the intramucosal lymphatics Tropical Sprue None Range from minimal changes in villous height and moderate epithelial cell damage to virtual absence of villi and elongated crypts with lymphocyte infiltration in the lamina propria Whipple Disease None Lamina propria densely infiltrated with periodic acid-Schiff–positive macrophages Villous structure possibly obliterated in severe lesions (eg, small-bowel follow-through, Enteroclysis , Diagnosis None -hydrogen breath tests are most commonly used. These tests are done to measure the exhaled hydrogen and methane produced by the bacterial degradation of carbohydrates. In patients with disaccharidase deficiencies, enteric bacteria degrade nonabsorbed carbohydrates in the colon, increasing exhaled hydrogen. The hydrogen breath tests have replaced bacterial cultures of aspirates taken during endoscopy for diagnosis of Small Intestinal Bacterial Overgrowth (SIBO) . The lactose-hydrogen breath test is useful only to confirm The Schilling testis done to assess malabsorption of vitamin B12. The 4 stages of this test are used to determine whether the deficiency results from pernicious anemia, pancreatic exocrine insufficiency, bacterial overgrowth, or ileal disease. Stage 1: The patient is given 1 mcg of radiolabeledcyanocobalaminorally concurrent with 1000 mcg of nonlabeled cobalamin IM to saturate hepatic binding sites. A 24-hour urine collection is analyzed for radioactivity; urinary excretion of<8% of the oral dose indicates malabsorption of cobalamin. Stage 2: If stage 1 is abnormal, the test is repeated with the addition of intrinsic factor. Pernicious anemia is present if intrinsic factor normalizes absorption. Stage 3: Stage 3 is done after adding pancreatic enzymes; normalization in this stage indicates cobalamin malabsorption secondary to pancreatic insufficiency. Stage 4: Stage 4 is done after antimicrobial therapy with anaerobic coverage; normalization after antibiotics suggests SIBO. Cobalamin deficiency secondary to ileal disease or ileal resection results in abnormalities in all stages. Tests for less common causes of malabsorption include serum gastrin (Zollinger-Ellison syndrome), intrinsic factor and parietal cell antibodies (pernicious anemia), sweat chloride (cystic fibrosis), lipoprotein electrophoresis (abetalipoproteinemia), and serum cortisol (Addison disease). To diagnose bile acid malabsorption, which may occur with diseases of the terminal ileum (eg, Crohn disease, extensive resection of terminal ileum), patients can be given a therapeutic trial of a bile acid binding resin (eg,cholestyramine). Alternatively, theselenium-75–labeled homocholic acid taurine (SeHCAT) test can be done. In this test,selenium-75–labeled synthetic bile acid is given orally and, after 7 days, the retained bile acid is measured with a whole-body scan or gamma camera. If bile acid absorption is abnormal, retention is less than 5%. The SeHCAT test is not available in many countries, including the United States. 