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Malabsorption A clinical spectrum of symptoms and signs resulting from defective mucosal absorption and excessive excretion of fat, carbohydrates, and proteins, with inadequate absorption of vitamins, minerals, electrolytes, and water. Although malabsorption generally denotes any defect in the absorptive process, the term strictly refers to the defective mucosal absorption of nutrients. Maldigestion denotes impaired nutrient hydrolysis. Aging and Digestion Although small-intestine mucosal surface area is reduced with age, the morphology of the small bowel does not differ from that in younger persons. The digestive and absorptive functions of the gastrointestinal (GI) system do not decline substantially with age. The only age-related defect in intestinal absorption is that of calcium, which is probably due to decreased renal production of 1,25-dihydroxycholecalciferol and reduced intestinal response. Small-intestine motility appears to remain intact with age. Aging does not significantly affect the structure and function of the exocrine pancreas. The main pancreatic duct may become ectatic and is associated with ductal hyperplasia and intralobular fibrosis. However, such morphologic changes are not known to cause clinical dysfunction; malabsorption and maldigestion only occur when > 90% of pancreatic exocrine function is lost. There are no age-related differences in the pancreatic output of trypsin, chymotrypsin, and lipase after maximal doses of secretin and cerulein. Etiology Malabsorption has many causes (see Table 111-1). Pancreatic insufficiency, such as occurs with chronic pancreatitis and pancreatic cancer, is the cause of malabsorption in 20 to 30% of cases in the elderly. A significant number of these patients have no history of typical pain or predisposing factors (eg, alcoholism). About 30% of malabsorption cases in elderly patients are due to anatomic abnormalities (eg, small-intestine diverticulosis, strictures, partial obstruction), which promote stasis of intestinal contents and predispose patients to the bacterial overgrowth syndrome. Another 20% of patients with malabsorption have bacterial overgrowth syndrome in the absence of anatomic abnormalities. This syndrome occurs when gastric acid secretion is inadequate. Pernicious anemia and vitamin B12 deficiency are common, suggesting that gastric atrophy and achlorhydria allow proliferation of gastric and small-intestine bacteria. Intestinal motility disorders may also impair bacterial clearance, which can lead to bacterial overgrowth. Malabsorption of fat, proteins, minerals, and vitamins often occurs after gastrectomies and small-intestine resections (enterectomy). A gastrectomy with vagotomy can result in rapid gastric emptying and transit through the small intestine. Nutritional deficiencies after a gastrectomy or small-intestine resection result from diminished absorption of iron, calcium, fat, and protein and are related to the extent of the gastrectomy, rapidity of intestinal transit, and the type of anastomosis. As a general rule, one third of the jejunum and ileum may be excised without seriously impairing nutrient absorption. More radical resection is tolerated poorly, and adults who have lost two thirds of the small intestine usually develop severe metabolic problems. After resection of the terminal ileum, absorption of vitamin B12 and bile acids is reduced. Resections of more than 100 cm of small intestine result in marked steatorrhea and a depleted bile salt pool. Typically, partial and total colectomy only temporarily diminish the absorption of water and some electrolytes. Total proctocolectomy produces only temporary malabsorption. Other causes of malabsorption include cirrhosis and biliary tract disease, which can result in impaired micelle formation. Intestinal mucosal abnormalities arising from celiac sprue (the cause in 30% of patients), tropical sprue, Whipple's disease, or Crohn's disease can also cause malabsorption. Obstruction of the intestinal lymphatic system, such as occurs in intestinal lymphangiectasia, results in lipoprotein malabsorption. Infestation with some intestinal parasites (eg, giardiasis, cryptosporidiosis) can rarely lead to malabsorption. Symptoms and Signs Often, an elderly patient with a malabsorption syndrome may only have weight loss or failure to maintain body weight, which leads to general debility. Often, symptoms may include diarrhea, greasy stools, abdominal bloating, and gas. Although diarrhea is not always present in persons with malabsorption, chronic diarrhea is the most common GI symptom of malabsorption to prompt an evaluation. Steatorrhea, which is due to the malabsorption of fat, is suggested by foul-smelling, bulky stools that are difficult to flush. Steatorrhea occurs when > 6% of dietary fat is excreted in the stool. Although physiologic steatorrhea can occur rarely in some conditions, steatorrhea is considered to be the hallmark of malabsorption. Abdominal bloating and excessive flatus suggest colonic fermentation of maldigested carbohydrates. In advanced malabsorption, severe vitamin and mineral deficiencies occur. Other clinical manifestations include anemia secondary to deficiencies in iron, folate, vitamin B12, or any combination of these micronutrients; easy bruising and bleeding secondary to vitamin K deficiency; muscular weakness and bone pain caused by vitamin D deficiency; and cramps, numbness, and paresthesias suggesting hypocalcemia and hypomagnesemia. Diagnosis The clinical features of the malabsorption syndromes are less obvious and more difficult to recognize in the elderly than in younger persons. Occasionally, the syndrome is only suspected when blood tests show deficiency states such as anemia, hypocalcemia, and hypoalbuminemia. Therefore, the physician should maintain a high index of suspicion. In many cases, the cause may be suggested by a history of lifelong symptoms of diarrhea exacerbated by gluten products, stomach and intestinal operations, use of drugs, or recurrent episodes of abdominal pain. Steatorrhea should be identified and is usually confirmed by a quantitative 72-hour stool collection. Severe fat malabsorption (fecal fat of >= 40 g) almost always indicates pancreatic insufficiency or small-intestine mucosal disease. The d-xylose test is a good, noninvasive way of differentiating pancreatitis (or another intraluminal etiology) from mucosal disease, especially if the cause is not evident from the clinical data. If severe steatorrhea is accompanied by a normal d-xylose test result, pancreatic disease should be suspected. Often, the combination of history of alcoholism, pancreatic calcifications, and recurrent abdominal pain can make the diagnosis of chronic pancreatitis apparent. If the diagnosis is in doubt, pancreatic insufficiency can be confirmed with the secretin stimulation test or with the bentiromide or pancreolauryl tests. Other intraluminal causes of malabsorption include inadequate bile salt concentrations from cirrhosis, severe parenchymal liver disease, and cholestasis. If severe steatorrhea is accompanied by an abnormal d-xylose test result, mucosal disease is suggested and an endoscopic biopsy should be performed. However, abnormal results of the d-xylose test can also be caused by bacterial overgrowth. Therefore, an aspirate can be collected during the biopsy to test for bacteria and parasites, particularly if bacterial overgrowth is suspected. If bacterial overgrowth syndrome is documented by culture or breath tests, a barium x-ray should be ordered to look for diverticula, blind loop syndrome, strictures, fistulas, and other anatomic abnormalities. If no anatomic abnormality that explains the malabsorption is found, pernicious anemia or systemic diseases should be suspected, and a Schilling test is recommended to differentiate between pernicious anemia, pancreatic insufficiency, and bacterial overgrowth. If pancreatic insufficiency needs to be further documented, pancreatic imaging studies are a reasonable first step. If these are not diagnostic, the patient should be tested for exocrine insufficiency. Most tests assess malabsorption of fat, which is easier to measure than malabsorption of other dietary components. Confirmation of carbohydrate malabsorption is not helpful once steatorrhea is documented. Because fecal nitrogen is difficult to measure, tests for protein absorption are rarely used. Blood tests: Although neither sensitive nor specific, some blood tests may be diagnostically helpful. Such tests include a complete blood cell count and peripheral smear; serum levels of iron, ferritin, vitamin B12, calcium, and albumin; and red blood cell (RBC) folate. Microcytic anemia without GI blood loss suggests iron malabsorption. Macrocytic anemia strongly indicates folate or vitamin B12 malabsorption. A low RBC folate level confirms folate malabsorption, which is common in mucosal disorders involving the jejunum. A low serum vitamin B12 level suggests pernicious anemia, bacterial overgrowth, or terminal ileal disease. A low serum albumin level may indicate poor nutritional intake. Determination of carotene, a precursor of fat-soluble vitamin A, is sometimes helpful. If dietary deficiency can be excluded in the elderly, serum carotene levels of < 0.6 mg/dL indicate mucosal malabsorption. Tests for steatorrhea: The qualitative Sudan stain is specific for dietary triglycerides and lipolytic metabolites. A stool specimen is examined microscopically after being heated in glacial acetic acid in the presence of Sudan III stain. Multiple orange-red globules indicate steatorrhea. When steatorrhea is < 10 g/24 hours, the estimated falsenegative rate is 25%. The correlation between this qualitative test and the quantitative fecal fat test is poor. The most accurate test for determining steatorrhea is a quantitative fecal fat test, which measures fatty acids from exogenous and endogenous sources. After the patient consumes a daily diet of 100 g of fat for at least 3 days, the total amount of fat in the stool collected during a 72-hour period is measured. Fecal fat > 6 g daily is abnormal. Fecal fat > 40 g daily suggests defective lipolysis (eg, due to pancreatic insufficiency) or massive ileal resection. The 14C-triolein breath test can confirm fat malabsorption. The patient ingests 60 g of labeled 14C-triolein, a triglyceride that undergoes lipid hydrolysis and is subsequently absorbed and metabolized, releasing CO2. Breath samples are then analyzed for radioactivity. The results may be erroneous in patients with diabetes mellitus, obesity, hyperlipidemia, thyroid disorders, chronic liver disease, or lung disease, because altered metabolism of triolein or impaired excretion of CO2 occurs in these conditions. Tests for mucosal diseases: The d-xylose absorption test is the best noninvasive method for assessing intestinal mucosal integrity. Xylose is a pentose that does not require pancreatic enzymes for digestion. Thus, this test helps differentiate maldigestion from malabsorption. A normal d-xylose test in the presence of steatorrhea indicates pancreatic exocrine insufficiency rather than small-intestine mucosal disease. This test has a reported 98% specificity and 91% sensitivity. The patient is given an oral dose of 25 g of d-xylose. A venous blood sample is taken 1 hour after ingestion, and urine is collected over 5 hours. A serum level of < 20 mg/dL and a d-xylose level of < 4 g in the urine collection indicate abnormal absorption of the pentose. Falsely low levels can occur in patients with renal diseases, bacterial overgrowth, ascites, portal hypertension, or delayed gastric emptying time. The Schilling test assesses malabsorption of vitamin B12 and can determine whether the deficiency is due to pernicious anemia, pancreatic exocrine insufficiency, bacterial overgrowth, or ileal disease. Controversy exists about the usefulness of this test. In this test, if there is normalization with the addition of pancreatic enzymes, cobalamin malabsorption is secondary to pancreatic insufficiency. Correction after antimicrobial therapy suggests bacterial overgrowth, whereas cobalamin deficiency secondary to ileal disease or ileal resection indicates abnormalities at all stages of absorption. Endoscopic small-bowel biopsy allows visual assessment of the small-intestine mucosa and can allow directed biopsies if there are areas of patchy involvement. Histologic features may establish a diagnosis of parasitic infection (eg, Giardia lamblia, Coccidiodes immitis, Cryptosporidia), amyloidosis, Whipple's disease, mastocytosis, lymphangiectasia, or collagenous sprue. In amyloidosis, deposits of amyloid are seen within the walls of the arterioles in the submucosa. In Whipple's disease, the lamina propria becomes infiltrated with periodic acid-Schiff-positive macrophages. In lymphangiectasia, markedly dilated lamina propria lymphatics are found together with edema and villous distortion. Villous atrophy is characteristic of celiac sprue but may be seen in tropical sprue, Crohn's disease, lymphoma, Whipple's disease, and bacterial overgrowth. Contrast small-intestine x-rays are not adequately sensitive for evaluating mucosal disease; their usefulness lies in the detection of anatomic abnormalities that predispose to bacterial overgrowth (eg, diverticula, surgically created stagnant loops, strictures, fistulas, ulcerations, dilated small-bowel loops). These x-rays can also demonstrate patchy or distal mucosal disease (eg, Crohn's disease). Tests for pancreatic insufficiency: The secretin test is the most sensitive test for demonstrating pancreatic exocrine insufficiency. A tube with distal aspiration holes is placed via fluoroscopy in the duodenum at the entrance of the pancreatic duct. Collection of the duodenal aspirate is performed after stimulation of pancreatic secretions by IV administration of secretin alone or with cholecystokinin or cerulein. If cholecystokinin or cerulein is given, the aspirate is measured for trypsin, amylase, or lipase. If secretin alone is given, the aspirate is measured for bicarbonate. Bicarbonate secretion is probably the single most useful measure of exocrine function. Most investigators consider a bicarbonate concentration < 70 mEq/L and a secretion volume < 2 mL/kg of body weight as abnormal. However, this test is invasive, time-consuming, expensive, and unavailable in most hospitals. Other tests for pancreatic function include the bentiromide test, which measures pancreatic chymotrypsin activity, and the pancreolauryl test, in which oral fluorescein dilaurate is hydrolyzed by pancreatic esterase. Para-aminobenzoic acid and fluorescein are measured in the urine, respectively. Both tests are sensitive for moderate to severe pancreatic insufficiency but are of limited value in mild pancreatic impairment. The serum trypsinogen test is a simple noninvasive radioimmunoassay blood test that may help diagnose chronic pancreatitis. A serum trypsinogen level of < 20 ng/mL (normal is 20 to 80 ng/mL) is characteristic of pancreatic insufficiency. Pancreatic calcifications on plain abdominal x-rays suggest chronic pancreatitis. However, calcifications are seen only when severe pancreatic damage has already occurred and are found in only 20 to 30% of patients with pancreatic insufficiency. Ultrasound and CT are useful in imaging the pancreas to exclude pancreatic cancer. Endoscopic retrograde cannulation of the pancreatic duct can demonstrate obstruction, irregularities, and narrowing of the main duct and side branches, which suggest chronic pancreatitis. However, this procedure is invasive and causes pancreatitis in 4% of patients. Tests for bacterial overgrowth: The diagnosis of bacterial overgrowth is best made with a direct quantitative bacterial count and/or positive aspirate culture. An aspirate is collected from the proximal small intestine, which is normally free of bacteria. An aspirate that contains > 105 organisms/mL suggests bacterial overgrowth syndrome. Bacteria commonly implicated are coliforms and other aerobic bacteria as well as anaerobic organisms (eg, bacteroides, lactobacilli, clostridia). The same aspirate can also be examined for giardiasis. Breath tests are sensitive, inexpensive, and generally acceptable to most patients. These tests measure the production of volatile metabolites produced by bacteria after the ingestion of fermentable substrates in a timed breath excretion collection. The acid breath test identifies abnormal bacterial deconjugation of previously administered 14Cglycocholic acid. The glycine residue is metabolized and results in 14CO2 in the breath. An early rise of 14CO2 within 6 hours indicates small-intestine bacterial overgrowth. However, this test has only a 65% sensitivity. The 14C d-xylose breath test depends on the ability of gram-negative aerobic bacteria to metabolize d-xylose, resulting in 14CO2 in the expired air after 60 minutes. This test has an overall sensitivity of 65 to 95%. Treatment The main objectives are correcting deficiencies of nutrients, vitamins, and trace minerals and identifying and treating the underlying causes. Patients with iron deficiency are given supplemental ferrous sulfate or gluconate tablets. Oral folic acid can be given to patients with folate deficiency, and intramuscular vitamin B12 injections can be given monthly to persons with cobalamin deficiency. Patients with marked steatorrhea require fat-soluble vitamin and calcium supplementation. A highprotein, low-fat diet and high-calorie dietary supplementation are recommended for patients with severe weight loss. A low-fat diet reduces steatorrhea and bile salt excretion, especially in patients with small-intestine resections. Medium-chain triglycerides, given as a dietary supplement, are preferred because they are hydrolyzed more readily by pancreatic lipase, and micelle formation is not necessary for their absorption. Parenteral nutrition may be considered in patients with severe malnutrition who are unresponsive to oral feeding. However, parenteral nutrition is reserved as the sole source of primary nutrients for persons with conditions in which the temporary avoidance of enteral feeding is necessary. In only rare conditions is long-term parenteral feeding appropriate.