Malabsorption Article from Specialty Labs
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Malabsorption
E. Robert Wassman, M.D.& Hermino R. Reyes, Ph.D.
A wide variety of disease states cause malabsorption as a primary or secondary feature. Malabsorption can be pancreatic, hepatic, or enteric in origin, and can be generalized or specific in nature. In general malabsorption, steatorrhea, defined as >5 g of fat in feces per 24 hours, is a major sign.1 The development of age-specific reference values for the fecal acid steatocrit permits the distinction of "physiological steatorrhea" during the first six months of life.2
In malabsorption of pancreatic origin, digestion and subsequent small bowel absorption is impaired. Creatorrhea, the presence of undigested meat fibers in the stool, can also be present. Pancreatic malabsorption is seen with pancreatitis, cancer of the pancreas, and cystic fibrosis (CF). CF can be differentiated by the measurement of sweat electrolytes, stool trypsin,1 or more recently, a specific DNA test for gene mutations.
Hepatic malabsorption, usually accompanied by other signs of liver disease, results from decreased availability of bile salts necessary for fat emulsification. It can occur in combination with pancreatic malabsorption when tumors obstruct drainage from both organs.1 Elevated plasma lathosterol measured by gas liquid chromatography has a 100% sensitivity and 82% specificity for bile acid malabsorption, and is simpler and less expensive than fecal bile acid determination, the 75SeHCAT test or the Schilling test.3
Enteric malabsorption occurs in a wide variety of conditions with normal digestion but reduced assimilation including blind loop syndrome (bacterial overgrowth), diverticulosis of the small intestines, Whipple disease, lymphoma, amyloidosis, shortened bowel length, celiac disease and other food sensitivities, radiation therapy, vasculitis, diabetes, carcinoid, hypogammaglobulinemia and other immunodeficiencies. Most have unique laboratory findings in addition to malabsorption. Enteric malabsorption can be distinguished from the pancreatic forms by the D-xylose absorption test which measures the urinary excretion of the sugar over five hours after ingestion of a 25 gram oral dose. Because pancreatic enzymes play no role in its absorption, the excretion of <3 g in this period is indicative of an enteric malabsorption; in the face of concomitant renal disease, serum concentrations should be simultaneously evaluated. Clinical associations of celiac disease (CD) can include mild weakness, bone pain, aphthous stomatitis, chronic diarrhea, abdominal bloating, progressive weight loss, dermatitis herpetiformis (DH), hyposplenism, IgA nephropathy, primary biliary cirrhosis, sclerosing cholangitis, Sjogren syndrome, Down syndrome and insulin-dependent diabetes mellitus.4-6 Genotyping for CD/DH susceptibility and immunoassays for gliadin, reticulin and endomysial autoantibodies are useful for predicting disease susceptibility and confirming a diagnosis of CD/DH, respectively.
Malabsorption is often accompanied by measurable deficiencies of the fat-soluble vitamins and other general findings related to nutritional deficits such as hypoproteinemia, hypoprothrombinemia and anemia. Many gastrointestinal disorders including gastric and other cancers, inflammatory bowel disease, celiac disease, tropical sprue, intestinal lymphangiectasia, graft versus host disease and a variety of infections and bacterial overgrowth (Whipple disease) can specifically lead to mucosal loss of protein. The cumbersome method of measuring 51chromium-labeled albumin in the stool is inferior to the simple analysis of a1-antitrypsin in the feces. The fact that it is neither reabsorbed nor subject to intestinal proteolysis allows the a1-antitrypsin clearance (grams excreted per 24 hrs multiplied by the ratio of fecal to serum a1-antitrypsin concentrations) to correlate well with the former test.1
In pernicious anemia, the classic example of a specific absorption defect, malabsorption of vitamin B12 reflects lack of the required transport vehicle, intrinsic factor. Acrodermatitis enteropathica, a severe autosomal recessive condition with skin excoriation and pustules, diarrhea and malabsorption, and infections, occurs in infants after weaning due to the lack of a specific zinc absorption factor. Resultant low zinc concentrations can be readily treated with zinc sulfate. Copper deficiency can reflect a similar specific absorption defect in Menkes disease/Occipital Horn syndrome or generalized malabsorption, and can be confused with child abuse. The detection and monitoring of defects of essential trace elements as a result of specific and general malabsorption or other causes was recently reviewed.7
Many conditions presenting with signs and/or symptoms of malabsorption, e.g., acute gastroenteritis and medications, can be associated with secondary intolerance to disaccharides which is often transient and associated with multiple deficiencies of the intestinal disaccharidases. Primary deficiencies of sucrase-isomaltase, lactase, trehalase and primary alactasia are distinct hereditary conditions. Stool pH <5.5 is suggestive of a disaccharidase deficiency, but is invalid in the presence of oral antibiotics, and higher values are not exclusionary. Semi-quantitative (Clinitest tablet, Ames) or quantitative chromatographic analysis demonstrating in excess of 0.5 g/dL of reducing substances in the stool is very helpful, but specific diagnosis requires enzymatic assay on intestinal biopsy material.1 A mutation at nucleotide 3298 in the sucrase subunit of the enzyme complex occurs in sucrase-isomaltase deficiency, and DNA analysis can avoid an invasive procedure.8
Non-invasive analysis of breath hydrogen (H2-BT) is now commonly used to diagnose carbohydrate malabsorption of many causes. H2-BT with D-xylose is simpler and more reliable than the traditional urinary test in celiac disease.7 Overall lactose intolerance is quite common occurring in 10% of Caucasians and over 70% of African-Americans and Asians. A novel automatic sampling system for H2-BT was used in Southern Chinese children to study lactose intolerance with a detection limit of 0.5 ppm H2 and intra-individual coefficients of variation <10%. At a cut-off of 20 ppm rise in H2, 78% of children and 63% of pre-term infants were lactose malabsorbers; whereas, only 18% of term Chinese infants exceeded the cut-off.9 Similarly, a H2-BT is used to diagnose rice carbohydrate malabsorption in Burma where 70% of children are rice-malabsorbers.10
Glucose-galactose malabsorption, a rare autosomal recessive disorder with severe osmotic diarrhea shortly after birth, is due to a missense mutation in the Na+ dependent glucose/galactose cotransporter (SGLT1); a PCR-based assay can be used in prenatal diagnosis.11
For information on Shwachman-Diamond Syndrome check out Shwachman-Diamond America
