AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Background

Malabsorption is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients by and infections of the gastrointestinal tract. The digestion or absorption of a single nutrient component may be impaired, as in lactose intolerance due to lactase deficiency. When a diffuse disorder, such as celiac disease or Crohn's disease, affects the intestine, the absorption of almost all nutrients is impaired.

While presenting symptoms, such as diarrhea and weight loss, may be common, the specific causes of malabsorption are usually established based on physiological evaluations. The treatment often depends on the establishment of a definitive etiology for malabsorption.

Pathophysiology

To understand the mechanisms of malabsorption, understanding the normal physiological process of digestion and absorption by the intestinal tract is necessary.
 
In general, the digestion and absorption of food materials can be divided into 3 major phases: luminal, mucosal, and postabsorptive. The luminal phase is the phase in which dietary fats, proteins, and carbohydrates are hydrolyzed and solubilized by secreted digestive enzymes and bile. The mucosal phase relies on the integrity of the brush-border membrane of intestinal epithelial cells to transport digested products from the lumen into the cells. In the postabsorptive phase, reassembled lipids and other key nutrients are transported via lymphatics and portal circulation from epithelial cells to other parts of the body.

Perturbation by disease processes in any of these phases frequently results in malabsorption.

CLINICAL

Section 3 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

History

The osmotic load resulting from the inability of the intestine to absorb certain nutrient elements causes the presenting symptoms. On occasion, the products of digestion produced by bacterial flora also result in a secretory reaction by the intestine.

• Diarrhea
• • Diarrhea is the most common symptomatic complaint.
  • Diarrhea frequently is watery, reflecting the osmotic load received by the intestine.
  • Bacterial action producing hydroxy fatty acids from undigested fat also can increase net fluid secretion from the intestine, further worsening the diarrhea.
• Steatorrhea
• • Steatorrhea is the result of fat malabsorption.
  • The hallmark of steatorrhea is the passage of pale, bulky, and malodorous stools.
  • Such stools often float on top of the toilet water and are difficult to flush. Also, patients find floating oil droplets in the toilet following defecation.
• Weight loss and fatigue
• • Weight loss is common and may be pronounced; however, patients may compensate by increasing their caloric consumption, masking weight loss from malabsorption.
  • The chance of weight loss increases in diffuse diseases involving the intestine, such as celiac disease and Whipple disease.
• Flatulence and abdominal distention
• • Bacterial fermentation of unabsorbed food substances releases gaseous products, such as hydrogen and methane, causing flatulence.
  • Flatulence often causes uncomfortable abdominal distention and cramps.
• Edema
• • Hypoalbuminemia from chronic protein malabsorption or from loss of protein into the intestinal lumen causes peripheral edema.
  • Extensive obstruction of the lymphatic system, as seen in intestinal lymphangiectasia, can cause protein loss.
  • With severe protein depletion, ascites may develop.
• Anemia
• • Depending on the cause, anemia resulting from malabsorption can be either microcytic (iron deficiency) or macrocytic (vitamin B-12 deficiency).
  • Iron deficiency anemia often is a manifestation of celiac disease.
  • Ileal involvement in Crohn disease or ileal resection can cause megaloblastic anemia due to vitamin B-12 deficiency.
• Bleeding disorders
• • Bleeding usually is a consequence of vitamin K malabsorption and subsequent hypoprothrombinemia.
  • Ecchymosis usually is the manifesting symptom, although, occasionally, melena and hematuria occur.
• Metabolic defects of bones
• • Vitamin D deficiency can cause bone disorders, such as osteopenia or osteomalacia.
  • Bone pain and pathological fractures may be observed.
  • Malabsorption of calcium can lead to secondary hyperparathyroidism.
• Neurological manifestations
• • Electrolyte disturbances, such as hypocalcemia and hypomagnesemia, can lead to tetany, manifesting as the Trousseau sign and the Chvostek sign.
  • Vitamin malabsorption can cause generalized motor weakness (pantothenic acid, vitamin D) or peripheral neuropathy (thiamine), a sense of loss for vibration and position (cobalamin), night blindness (vitamin A), and seizures (biotin).

See related CME at Efficient Diagnosis of Suspected Functional Bowel Disorders.

Physical

• General physical examination
• • Patients may have orthostatic hypotension.
  • Patients may complain of fatigue.
  • Signs of weight loss, muscle wasting, or both may be present.
  • Patients may have signs of loss of subcutaneous fat.
• Abdominal examination
• • The abdomen may be distended, and bowel sounds may be hyperactive.
  • Ascites may be present in severe hypoproteinemia.
• Dermatological manifestations
• • Pale skin may reveal anemia.
  • Ecchymoses due to vitamin K deficiency may be present.
  • Dermatitis herpetiformis, erythema nodosum, and pyoderma gangrenosum may be present.
  • Pellagra, alopecia, or seborrheic dermatitis may be present.
• Neurological examination
• • Motor weakness, peripheral neuropathy, or ataxia may be present.
  • The Chvostek sign or the Trousseau sign may be evident due to hypocalcemia or hypomagnesemia.
• Cheilosis, glossitis, or aphthous ulcers of the mouth
• Peripheral edema

Causes

The best way to classify the numerous causes of malabsorption is to consider the 3 phases of digestion and absorption.

• Luminal phase
• • Impaired nutrient hydrolysis
  • • The most common cause for impaired nutrient hydrolysis is pancreatic insufficiency due to chronic pancreatitis, pancreatic resection, pancreatic cancer, or cystic fibrosis. The resultant deficiencies in lipase and proteases lead to lipid and protein malabsorption, respectively.
    • Inactivation of pancreatic enzymes by gastric hypersecretion, as seen in Zollinger-Ellison syndrome, is another cause.
    • Inadequate mixing of nutrients, bile, and pancreatic enzymes, as seen in rapid intestinal transit, gastrojejunostomy, total and partial gastrectomy, or intestinal resection after mesenteric emboli or thrombosis, also causes impaired hydrolysis.
    • Rarely, a failure to convert a proenzyme to active form, such as enterokinase and trypsinogen deficiencies, also can cause protein maldigestion and malabsorption.
  • Impaired micelle formation
  • • Impaired micelle formation causes a problem in fat solubilization and subsequent fat malabsorption. This impairment is due to different reasons, including (1) decreased bile salt synthesis from severe parenchymal liver disease (eg, cirrhosis); (2) impaired bile secretion from biliary obstruction or cholestatic jaundice (eg, primary biliary cirrhosis, primary sclerosing cholangitis); (3) impaired enterohepatic bile circulation, as seen in small bowel resection or regional enteritis; or (4) bile salt deconjugation due to small bowel bacterial overgrowth.
    • Stasis of intestinal content caused by a motor abnormality (eg, scleroderma, diabetic neuropathy, intestinal obstruction), an anatomical abnormality (eg, small bowel diverticula, stricture, ischemia, blind loops), or small bowel contamination from enterocolonic fistulas can cause bacterial overgrowth.
  • Luminal availability and processing
  • • Luminal bacterial overgrowth can cause a decrease in the availability of substrates, including carbohydrates, proteins, and vitamins (eg, vitamin B-12, folate).
    • Vitamin B-12 deficiency due to pernicious anemia is caused by a lack of intrinsic factor and by pancreatic enzyme deficiency.
• Mucosal phase
• • Impaired brush-border hydrolase activity
  • • Disaccharidase deficiency can lead to disaccharide malabsorption.
    • Lactase deficiency, either primary or secondary, is the most common form of disaccharidase deficiency. Genetic factors determine primary lactase deficiency. Secondary lactase deficiency can be due to acute gastroenteritis (rotavirus and giardia infection), chronic alcoholism, celiac sprue, radiation enteritis, regional enteritis, or AIDS enteropathy.
    • Immunoglobulin A (IgA) deficiency (most common immunodeficiency) is due to decreased or absent serum and intestinal IgA, which clinically appears similar to celiac disease and is unresponsive to a gluten-free diet.
    • Acrodermatitis enteropathica is an autosomal recessive disease with selective inability to absorb zinc, leading to villous atrophy and acral dermatitis.
    • Autoimmune enteropathy primarily diagnosed in children presenting with intractable secretory diarrhea and villous atrophy. Autoimmune enteropathy is due to antibodies directed against intestinal epithelial and goblet cells. Additional cell types affected by autoantibodies include islet and parietal cells.
    • Other carbohydrase deficiencies, such as sucrase-isomaltase deficiency, may be the cause.
  • Impaired nutrient absorption
  • • Nutrient malabsorption is due to inherited or acquired defects.
    • Inherited defects include glucose-galactose malabsorption, abetalipoproteinemia, cystinuria, and Hartnup disease.
    • Acquired disorders are far more common and are caused by the following: (1) decreased absorptive surface area, as seen in intestinal resection of intestinal bypass; (2) damaged absorbing surface, as seen in celiac sprue, tropical sprue, Crohn's disease, AIDS enteropathy, chemotherapy, or radiation therapy; (3) infiltrating disease of the intestinal wall, such as lymphoma and amyloidosis; and (4) infections, including bacterial overgrowth, giardiasis, Whipple's disease, cryptosporidiosis, and microsporidiosis.
• Postabsorptive phase: Obstruction of the lymphatic system, both congenital (eg, intestinal lymphangiectasia, Milroy disease) and acquired (eg, Whipple disease, neoplasm [including lymphoma], tuberculosis), impairs the absorption of chylomicrons and lipoproteins and may cause fat malabsorption or a protein-losing enteropathy.

DIFFERENTIALS

Section 4 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Other Problems to be Considered

Amino acid deficiencies (cystinuria)
Autoimmune enteropathy
Sucrose-isomaltase deficiency
Tropical jejunitis

WORKUP

Section 5 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Lab Studies

• Hematological 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.

Imaging Studies

• 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 dilation and diverticulosis are frequently identified in scleroderma.
  • Regional enteritis of the small intestine can lead to stricture, ulceration, and fistula formation.
  • Other anatomical 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.

Other Tests

• 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.
  • 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.

Procedures

• Upper endoscopy with small bowel mucosal biopsy
• • Establishing a definitive diagnosis of malabsorption of the mucosal phase often can be achieved by histological 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.

Histologic Findings

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.

TREATMENT

Section 6 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Medical Care

Two basic principles underlie the management of patients with malabsorption, as follows: (1) the correction of nutritional deficiencies, and (2) when possible, the treatment of causative diseases.

• Nutritional support
• • Supplementing various minerals, such as calcium, magnesium, iron, and vitamins, which may be deficient in malabsorption, is important.
  • Caloric and protein replacement also is essential.
  • Medium-chain triglycerides can be used as fat substitutes because they do not require micelle formation for absorption and their route of transport is portal rather than lymphatic.
  • In severe intestinal disease, such as massive resection and extensive regional enteritis, parenteral nutrition may become necessary.
• Treatment of causative diseases
• • A gluten-free diet helps treat celiac disease.
  • Similarly, a lactose-free diet helps correct lactose intolerance; supplementing the first bite of milk-containing food products with Lactaid also helps.
  • Protease and lipase supplements are the therapy for pancreatic insufficiency.
  • Antibiotics are the therapy for bacterial overgrowth.
  • Corticosteroids, anti-inflammatory agents, such as mesalamine, and other therapies are used to treat regional enteritis.

FOLLOW-UP

Section 7 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Patient Education

• For excellent patient education resources, visit eMedicine's Esophagus, Stomach, and Intestine Center and Crohn Disease Center. Also, see eMedicine's patient education articles Celiac Sprue and Crohn Disease.

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

• Bai JC. Malabsorption syndromes. Digestion. Aug 1998;59(5):530-46. [Medline].
• Born P, Sekatcheva M, Rosch T, et al. Carbohydrate malabsorption in clinical routine: a prospective observational study. Hepatogastroenterology. Sep-Oct 2006;53(71):673-7.
• Camilleri M. Gastrointestinal problems in diabetes. Endocrinol Metab Clin North Am. Jun 1996;25(2):361-78. [Medline].
• Ciclitira PJ. AGA technical review on Celiac Sprue. American Gastroenterological Association. Gastroenterology. May 2001;120(6):1526-40. [Medline].
• Donner CS. Pathophysiology and therapy of chronic radiation-induced injury to the colon. Dig Dis. Jul-Aug 1998;16(4):253-61. [Medline].
• Doty JE, Fink AS, Meyer JH. Alterations in digestive function caused by pancreatic disease. Surg Clin North Am. Jun 1989;69(3):447-65. [Medline].
• Farthing MJ. Giardiasis. Gastroenterol Clin North Am. Sep 1996;25(3):493-515. [Medline].
• Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. Feb 2001;120(3):636-51. [Medline].
• Gudmand-Hoyer E, Skovbjerg H. Disaccharide digestion and maldigestion. Scand J Gastroenterol Suppl. 1996;216:111-21. [Medline].
• Hansson GC. Cystic fibrosis and chloride-secreting diarrhoea. Nature. Jun 23 1988;333(6175):711. [Medline].
• Hirschowitz BI. Zollinger-Ellison syndrome: pathogenesis, diagnosis, and management. Am J Gastroenterol. Apr 1997;92(4 Suppl):44S-48S; discussion 49S-50S. [Medline].
• Holt PR. Diarrhea and malabsorption in the elderly. Gastroenterol Clin North Am. Jun 2001;30(2):427-44. [Medline].
• Husebye E. Gastrointestinal motility disorders and bacterial overgrowth. J Intern Med. Apr 1995;237(4):419-27. [Medline].
• Janecki AJ. Why should a clinician care about the molecular biology of transport?. Curr Gastroenterol Rep. 2000;2(5):378-86. [Medline].
• Karras PJ, Pfeifer MA. Diabetic gastrointestinal autonomic neuropathy. Curr Ther Endocrinol Metab. 1997;6:462-5. [Medline].
• Kastin DA, Buchman AL. Malnutrition and gastrointestinal disease. Curr Opin Gastroenterol. Mar 2002;18(2):221-8. [Medline].
• Kelly KJ. Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr. 2000;30 Suppl:S28-35. [Medline].
• Lai Ping So A, Mayer L. Gastrointestinal manifestations of primary immunodeficiency disorders. Semin Gastrointest Dis. Jan 1997;8(1):22-32. [Medline].
• Leffler D, Saha S, Farrell RJ. Celiac disease. Am J Manag Care. Dec 2003;9(12):825-31; quiz 832-3. [Medline].
• Levy E. The genetic basis of primary disorders of intestinal fat transport. Clin Invest Med. Oct 1996;19(5):317-24. [Medline].
• Lindley KJ, Macdonald S. Malabsorption in children. Practitioner. Mar 2001;245(1620):162-4, 166, 169-70 passim. [Medline].
• Lock G, Holstege A, Lang B, et al. Gastrointestinal manifestations of progressive systemic sclerosis. Am J Gastroenterol. May 1997;92(5):763-71. [Medline].
• Lovat LB, Pepys MB, Hawkins PN. Amyloid and the gut. Dig Dis. May-Jun 1997;15(3):155-71. [Medline].
• Meysman M, Debeuckelaer S, Reynaert H, et al. Systemic amyloidosis-induced diarrhea in sex-linked agammaglobulinemia. Am J Gastroenterol. Aug 1993;88(8):1275-7. [Medline].
• Owens SR, Greenson JK. The pathology of malabsorption: current concepts. Histopathology. Jan 2007;50(1):64-82. [Medline].
• Parnell ND, Ciclitira PJ. Review article: coeliac disease and its management. Aliment Pharmacol Ther. Jan 1999;13(1):1-13. [Medline].
• Pelletier VA, Galeano N, Brochu P, et al. Secretory diarrhea with protein-losing enteropathy, enterocolitis cystica superficialis, intestinal lymphangiectasia, and congenital hepatic fibrosis: a new syndrome. J Pediatr. Jan 1986;108(1):61-5. [Medline].
• Perri F, Clemente R, Festa V, et al. Pancreatic exocrine function tests. Scand J Gastroenterol. Oct 1998;33(10):1118-20. [Medline].
• Potter GD. Bile acid diarrhea. Dig Dis. Mar-Apr 1998;16(2):118-24. [Medline].
• Ramaiah C, Boynton RF. Whipple's disease. Gastroenterol Clin North Am. Sep 1998;27(3):683-95, vii. [Medline].
• Rose S, Young MA, Reynolds JC. Gastrointestinal manifestations of scleroderma. Gastroenterol Clin North Am. Sep 1998;27(3):563-94. [Medline].
• Saltzman JR, Russell RM. Nutritional consequences of intestinal bacterial overgrowth. Compr Ther. 1994;20(9):523-30. [Medline].
• Slater GH, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. Jan 2004;8(1):48-55; discussion 54-5. [Medline].
• Vardy PA, Lebenthal E, Shwachman H. Intestinal lymphagiectasia: a reappraisal. Pediatrics. Jun 1975;55(6):842-51. [Medline].
• Vesy CJ, Peterson WL. Review article: the management of Giardiasis. Aliment Pharmacol Ther. Jul 1999;13(7):843-50. [Medline].
• Virally-Monod M, Tielmans D, Kevorkian JP, et al. Chronic diarrhoea and diabetes mellitus: prevalence of small intestinal bacterial overgrowth. Diabetes Metab. Dec 1998;24(6):530-6. [Medline].
• Washington K, Stenzel TT, Buckley RH, et al. Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia. Am J Surg Pathol. Oct 1996;20(10):1240-52. [Medline].

Article Last Updated: Aug 14, 2008