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Overview of Malabsorption

By

Zubair Malik

, MD, Lewis Katz School of Medicine at Temple University

Reviewed/Revised Mar 2023
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Topic Resources

Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport.

Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats), micronutrients (eg, vitamins, minerals), or both, causing excessive fecal excretion, nutritional deficiencies, and gastrointestinal (GI) symptoms. Malabsorption may be global, with impaired absorption of almost all nutrients, or partial (isolated), with malabsorption of only specific nutrients.

Pathophysiology of Malabsorption

Digestion and absorption occur in three phases:

  • Intraluminal hydrolysis of fats, proteins, and carbohydrates by enzymes—bile salts enhance the solubilization of fat in this phase

  • Digestion by brush border enzymes and uptake of end-products

  • Lymphatic transport of nutrients

The term malabsorption is commonly used when any of these phases is impaired, but, strictly speaking, impairment of phase 1 is maldigestion rather than malabsorption.

Digestion of fats

Pancreatic enzymes (lipase and colipase) split long-chain triglycerides into fatty acids and monoglycerides, which combine with bile acids and phospholipids to form micelles that pass through jejunal enterocytes. Absorbed fatty acids are resynthesized and combined with protein, cholesterol, and phospholipid to form chylomicrons, which are transported by the lymphatic system. Medium-chain triglycerides are absorbed directly.

Unabsorbed fats trap fat-soluble vitamins (A, D, E, K) and possibly some minerals, causing deficiency. Bacterial overgrowth results in deconjugation and dehydroxylation of bile salts, limiting the absorption of fats. Unabsorbed bile salts stimulate water secretion in the colon, causing diarrhea.

Digestion of carbohydrates

The pancreatic enzyme amylase and brush border enzymes on microvilli lyse carbohydrates and disaccharides into constituent monosaccharides. Colonic bacteria ferment unabsorbed carbohydrates into carbon dioxide, methane, hydrogen, and short-chain fatty acids (butyrate, propionate, acetate, and lactate). These fatty acids cause diarrhea. The gases cause abdominal distention and bloating.

Digestion of proteins

Gastric pepsin initiates digestion of proteins in the stomach (and also stimulates release of cholecystokinin that is critical to the secretion of pancreatic enzymes). Enterokinase, a brush border enzyme, activates trypsinogen into trypsin, which converts many pancreatic proteases into their active forms. Active pancreatic enzymes hydrolyze proteins into oligopeptides, which are absorbed directly or hydrolyzed into amino acids.

Etiology of Malabsorption

Malabsorption has many causes (see table ). Some malabsorptive disorders (eg, celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease ) impair the absorption of most nutrients, vitamins, and trace minerals (global malabsorption); others (eg, pernicious anemia) are more selective.

Acute bacterial, viral, and parasitic infections (see also Overview of Gastroenteritis Overview of Gastroenteritis Gastroenteritis is inflammation of the lining of the stomach and small and large intestines. Most cases are infectious, although gastroenteritis may occur after ingestion of drugs, medications... read more ) may cause transient malabsorption, probably as a result of temporary, superficial damage to the villi and microvilli.

Table

Symptoms and Signs of Malabsorption

The effects of unabsorbed substances, especially in global malabsorption, include diarrhea, steatorrhea, abdominal bloating, and gas. Other symptoms result from nutritional deficiencies. Patients often lose weight despite adequate food intake.

Chronic diarrhea is the most common symptom and is what usually prompts evaluation of the patient. Steatorrhea—fatty stool, the hallmark of malabsorption—occurs when > 7 g/day of fat are excreted. Steatorrhea causes foul-smelling, pale, bulky, and greasy stools.

Table

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 Chronic Pancreatitis Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine... read more usually have had prior bouts of acute pancreatitis. Patients with celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease can present with classic lifelong diarrhea exacerbated by gluten products and may have dermatitis herpetiformis. Patients with cirrhosis and pancreatic cancer can present with jaundice. Abdominal distention, excessive flatus, and watery diarrhea occurring 30 to 90 minutes after carbohydrate ingestion suggest deficiency of a disaccharidase enzyme, usually lactase. Previous extensive abdominal operations suggest short bowel syndrome Short Bowel Syndrome Short bowel syndrome is malabsorption resulting from extensive resection of the small bowel (usually more than two thirds the length of the small intestine). Symptoms depend on the length and... read more .

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.

Suggested evaluation for malabsorption

Suggested evaluation for malabsorption

Macrocytic anemia Megaloblastic Macrocytic Anemias Megaloblastic anemias result most often from deficiencies of vitamin B12 and folate. Ineffective hematopoiesis affects all cell lines but particularly red blood cells. Diagnosis is usually based... read more 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, celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more Celiac Disease , tropical sprue Tropical Sprue Tropical sprue is a rare acquired disease, probably of infectious etiology, characterized by malabsorption and megaloblastic anemia. Diagnosis is clinical and by small-bowel biopsy. Treatment... read more , Whipple disease Whipple Disease Whipple disease is a rare systemic illness caused by the bacterium Tropheryma whipplei. Main symptoms are arthritis, weight loss, abdominal pain, and diarrhea. Diagnosis is by small-bowel... read more ). Low B12 levels can occur in pernicious anemia, chronic pancreatitis Chronic Pancreatitis Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine... read more , small intestinal bacterial overgrowth (SIBO) Small Intestinal Bacterial Overgrowth (SIBO) Small intestinal bacterial overgrowth can result from alterations in intestinal anatomy or gastrointestinal motility, or lack of gastric acid secretion. This condition can lead to vitamin deficiencies... read more , and terminal ileal disease. A combination of low B12 and high folate levels is suggestive of SIBO Small Intestinal Bacterial Overgrowth (SIBO) Small intestinal bacterial overgrowth can result from alterations in intestinal anatomy or gastrointestinal motility, or lack of gastric acid secretion. This condition can lead to vitamin deficiencies... read more , because intestinal bacteria use vitamin B12 and synthesize folate.

Microcytic anemia suggests iron deficiency, which may occur with celiac disease. Albumin is a general indicator of nutritional state. Low albumin can result from poor intake, decreased synthesis in cirrhosis, or protein wasting. Low serum carotene (a precursor of vitamin A) suggests malabsorption if intake is adequate.

Confirming malabsorption

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 fat from 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 smear is 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 chymotrypsin in 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.

The D-xylose absorption test can 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.

Diagnosing the cause of malabsorption

More specific diagnostic tests (eg, upper endoscopy, colonoscopy, barium x-rays) are indicated to diagnose several causes of malabsorption.

Upper endoscopy with 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.

Histologic features on small-bowel biopsy (see table ) can establish the specific mucosal disease.

Table

Small-Bowel Mucosal Histology in Certain Malabsorptive Disorders

Disorder

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

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

Dilation and ectasia of the intramucosal lymphatics

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

Lamina propria densely infiltrated with periodic acid-Schiff–positive macrophages

Villous structure possibly obliterated in severe lesions

Small-bowel x-rays (eg, small-bowel follow-through, enteroclysis Enteroclysis X-ray and other imaging contrast studies visualize the entire gastrointestinal tract from pharynx to rectum and are most useful for detecting mass lesions and structural abnormalities (eg, tumors... read more Enteroclysis , CT enterography CT enterography and MR enterography X-ray and other imaging contrast studies visualize the entire gastrointestinal tract from pharynx to rectum and are most useful for detecting mass lesions and structural abnormalities (eg, tumors... read more CT enterography and MR enterography , magnetic resonance enterography CT enterography and MR enterography X-ray and other imaging contrast studies visualize the entire gastrointestinal tract from pharynx to rectum and are most useful for detecting mass lesions and structural abnormalities (eg, tumors... read more CT enterography and MR enterography ) can detect anatomic conditions that predispose to bacterial overgrowth. These include jejunal diverticula, fistulas, surgically created blind loops and anastomoses, ulcerations, and strictures. These imaging studies may also detect mucosal abnormalities. Abdominal flat plate x-rays may show pancreatic calcifications indicative of chronic pancreatitis. Barium contrast studies X-Ray Contrast Studies of the Abdomen X-ray and other imaging contrast studies visualize the entire gastrointestinal tract from pharynx to rectum and are most useful for detecting mass lesions and structural abnormalities (eg, tumors... read more X-Ray Contrast Studies of the Abdomen of the small bowel are neither sensitive nor specific but may show findings suggestive of mucosal disease (eg, dilated small-bowel loops, thinned or thickened mucosal folds, coarse fragmentation of the barium column). CT, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography can establish the diagnosis of chronic pancreatitis.

Tests for pancreatic insufficiency Diagnosis Chronic pancreatitis is persistent inflammation of the pancreas that results in permanent structural damage with fibrosis and ductal strictures, followed by a decline in exocrine and endocrine... read more (eg, secretin stimulation test, bentiromide test, pancreolauryl test, serum trypsinogen, fecal elastase, fecal chymotrypsin) are done if history is suggestive but are not sensitive for mild pancreatic disease.

Breath tests help diagnose bacterial overgrowth. The glucose-hydrogen and lactulose-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 SIBO Small Intestinal Bacterial Overgrowth (SIBO) Small intestinal bacterial overgrowth can result from alterations in intestinal anatomy or gastrointestinal motility, or lack of gastric acid secretion. This condition can lead to vitamin deficiencies... read more . The lactose-hydrogen breath test is useful only to confirm lactase deficiency Carbohydrate Intolerance Carbohydrate intolerance is the inability to digest certain carbohydrates due to a lack of one or more intestinal enzymes. Symptoms include diarrhea, abdominal distention, and flatulence. Diagnosis... read more and is not used as an initial diagnostic test in the evaluation of malabsorption.

The Schilling test is 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 radiolabeled cyanocobalamin orally 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, the selenium-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.

Drugs Mentioned In This Article

Drug Name Select Trade
Colief, Lac-Dose , Lactaid, Lactaid Fast Act, Lactrase
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
A Mulsin, Aquasol A, Dofsol-A
ChiRhoStim , SecreFlo
Acilac, Cephulac, Cholac, Chronulac, Constilac, Constulose, Enulose, Generlac, Kristalose
B-12 Compliance Kit, B-12 Injection Kit, CaloMist, Cyomin, Dodex, LA-12 , Nascobal, Nutri-Twelve , Physicians EZ Use B-12, Primabalt
Locholest , Locholest Light, Prevalite , Questran, Questran Light
Selepen
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