CLASSIFICATION OF THE MALABSORPTION SYNDROMES



A very large number of disorders can produce or be associated with intestinal malabsorption, varying from specific genetic defects to acquired diffuse mucosal diseases. It will not be possible to discuss all of these entities in this section, which is devoted to a general understanding of malabsorption, but they are described in detail inthe articles to which reference is made at the end of this section. In general it is useful to think of malabsorption as resulting from abnormalities in one or more of the normal processes of digestion and absorption described earlier.

Inadequate Digestion. Ingested food must be broken down to its proper components for ab­sorption through intraluminal or surface enzy­matic processes. The exocrine secretion of the pancreas, described in Chapter 42, is of particular importance in the supply of lipase, colipase, and certain proteases, especially trypsin. One of the cardinal manifestations of chronic pancreatitis, either acquired or secondary to cystic fibrosis, is malabsorption. Even in the presence of normal pancreatic secretion of lipase, however, a gastri­noma (the Zollinger-Ellison syndrome) may stim­ulate enough gastric acid to lower the duodenal pH sufficiently to impair the activity of lipase and produce fat malabsorption.

The pancreatic component of fat digestion must be supplemented with a sufficient concentration of intraluminal bile salts for normal lipolysis and micelle formation. Inadequacy of bile salts can re­sult from (a) decreased synthesis by the liver, al­though this is rarely severe enough to result in major malabsorption; (b) prolonged cholestasis (see Chapter 49) especially in biliary cirrhosis; (c) deconjugation of the bile salts within the intestine by bacterial action in the bacterial overgrowth syndrome; or (d) interference in the ileal reab-sorption of bile salts for recycling, either due to the use of cholestyramine or more commonly in the presence of ileal disease or an ileal bypass. In these circumstances, the liver is not able to syn­thesize enough bile salts de novo to maintain crit­ical intraluminal levels so that maldigestion and malabsorption of fat and fat-soluble substances (e.g., vitamins A, D, E, and K) occur.
In addition to these more global disorders of digestion associated with deficiencies of pan­creatic enzymes or bile salts, more selective de­fects in digestion can occur. For example, defi­ciency of lactase, an intestinal brush border enzyme that normally hydrolyzes lactose to glu­cose and galactose, impairs the absorption of this disaccharide and may result in milk intolerance with symptoms of flatulence, distention, and diar­rhea. Lactase deficiency may be inherited (lactase deficiency is common in certain ethnic groups such as blacks and Orientals) or may occur sec­ondary to other causes of diffuse mucosal injury (e.g., celiac disease).

Inadequate Absorption. The components of food may not be adequately absorbed even after they have been normally digested. This may result from an insufficient available absorptive surface even though that remaining is normal. The sim­plest example is that of the postsurgical short bowel syndrome, which may follow surgery for mesenteric infarction or bypass” surgery for mor­bid obesity or Crohn’s disease.

Conversely, the absorptive surface may be nor­mal in area but be defective in function. This type of defect can be within the mucosal cell and then is usually highly specific and genetic in origin. Examples are selective absorptive defects for cer­tain amino acids in cystinuria and Hartnup dis­ease and for fat in abetalipoproteinemia, due to defective intracellular synthesis of apolipopro-teins. Selective defects can also be acquired, such as the reduced absorption of calcium when there is insufficient synthesis of 1,25-dihydroxycholecalciferol.

More frequently malabsorption, especially that of fat, is found in conditions in which there is a diffuse disease process involving the small intes­tinal mucosa and/or submucosa. Several causes of such diffuse injury are recognized although the mechanisms involved are often obscure:
Immunologic or Allergic Injury. It is thought that gluten-sensitive enteropathy (to be discussed sub­sequently) falls in this category, as well as pos­sibly some forms of the rare disorder eosinophilic enteritis.

Irifections and IriFESTATioNS. Whipple’s disease is a systemic disorder, the presumed bacterial etiology of which has not been clearly defined. In this disorder marked by malabsorption, the intes­tinal submucosa is packed with macrophages con­taining PAS-staining granules. Patients may also have fever, arthralgias, lymphadenopathy, pig­mentation changes, and neurological manifesta­tions. Whipple’s disease is rare, but the diagnosis is important, since it usually responds to pro­longed antibiotic therapy. Infestation with Giar-dia lamblia may be sufficient to cause mal­absorption, although flatulence, nausea, and diar­rhea are more common symptoms. In addition to causing deconjugation of bile salts, bacterial ov­ergrowth may also produce diffuse mucosal in­jury.
InriLTRATivE Disorders. The mucosa and/or sub­mucosa may be diffusely infiltrated in a number of disorders sufficient to impair its absorptive function. Examples include primary lymphoma of the bowel, particularly important as a cause of malabsorption in certain parts of the world such as the Near East, and such rare disorders as sys­temic mastocytosis and amyloidosis.

Fibrosis. The intestinal wall may become thick­ened and fibrotic in such disorders as systemic sclerosis and radiation injury. The causes of im­paired absorption may be complex in these enti­ties, however, and may result in part from abnor­mal motility and bacterial overgrowth.

Lymphatic Obstruction. After their absorption, long chain fatty acids are largely resynthesized as triglycerides and secreted into the lymphatics as chylomicrons or as very low density lipoproteins (VLDL). Diffuse obstructive lesions of the mes­enteric lymphatics can therefore impair fat ab­sorption. This is not infrequently a second cause of malabsorption in diffuse intestinal lymphoma and may also occur in Whipple’s disease and in the rare congenital disorder lymphangiectasia. The latter entity more commonly presents as pro­tein-losing enteropathy with secondary hypoalbuminemia.

Multiple Mechanisms. In view of the complex­ity of the digestive and absorptive processes, it is not surprising that a number of disorders may im­pair two or more steps. For example after subtotal gastrectomy with a gastroenterostomy (Billroth II procedure) a modest degree of malabsorption is very common. This may result from rapid gastric emptying and rapid intestinal transit, poor mixing of the pancreatic and biliary secretions from the blind duodenal loop with intestinal contents, de­creased stimulus for pancreatic and biliary secre­tion due to decreased release of secretin and cho-lecystokinin, and bacterial overgrowth due to stasis in the afferent blind loop. As noted, bac­terial overgrowth itself not only deconjugates bile salts but may cause diffuse injury to the intestinal epithelium. In diabetes mellitus there may be an associated exocrine deficiency of the pancreas and/or a motility disorder of the small intestine presumed to be due to diabetic neuropathy of the autonomic nervous system. This may be associ­ated with bacterial overgrowth due to stasis.

drugs have been shown to cause malabsorption of specific dietary elements, some of which are listed in Table 36-4.
Hyperabsorptive Malabsorption. Although we are accustomed to think of malabsorption as too little absorption, it can also represent too much absorption. In hemochromatosis, for example, there is inherited continued excessive absorption of iron. In hypervitaminosis D there is excessive absorption of calcium. Enteric hyperoxaluria is an acquired abnormality characterized by excessive absorption of dietary oxalate, largely in the colon, and results in a tendency to form calcium oxalate kidney stones.
Drug-induced Malabsorption. A number of