DISORDERS ASSOCIATED WITH MALABSORPTION



A very large number of disorders may result in intestinal malabsorption of varying degrees of se­verity. Some but not all of these have been listed in as examples of the potential causes of the syndrome. This section will discuss only two of these entities, celiac sprue and the bacterial overgrowth syndrome. Other specific disorders are discussed elsewhere in this book or are dis­cussed in detail in the appended references.

Celiac Sprue (Gluten-sensitive Enteropathy, nontropical Sprue). Celiac sprue is a chronic, seemingly familial disorder associated with a life­long sensitivity to dietary gluten, a protein found in wheat and wheat products. When this protein (or certain peptides derived from it) is ingested, a diffuse mucosal injury results that is character­istic but nonspecific. The villi are shortened and blunted with decreased absorptive surface area, the crypts are hyperplastic, and the lamina pro­pria is usually heavily infiltrated with lympho­cytes.

Pathogenesis. The pathogenesis of the injury has not been established, although the best evidence suggests an immunological mechanism. Patients with celiac sprue have a high prevalence of cer­tain histocompatibility types (HLA-B8 and Dw3), suggesting a linkage on chromosome 6 and strengthening the possibility of an immunological origin. On careful examination as many as 10 percent of firstdegree relatives of patients with celiac sprue may have the disorder. A second hypothesis postulates that an incomplete hydrolysis of pep­tides derived from gluten leads to the accumu­lation of toxic intermediates that directly injure the mucosal cell and that the immunological phe­nomena are secondary to this direct cell injury. Whatever the cause, it is known that the lesion is locally produced, disappears when gluten is with­drawn, and recurs within a few days when gluten is reintroduced. The pathogenesis of the resulting malabsorption is largely that of a diffuse mucosal abnormality. It has also been suggested that the abnormal mucosa has a reduced ability to secrete secretin and cholecystokinin-pancreozymin and therefore that pancreatic and biliary functions are secondarily impaired.

Symptoms and Signs. The symptoms and signs of celiac sprue are largely those that have been de­scribed for malabsorption in general. Symptoms tend to be more severe in childhood, diminishing after adolescence. Once again it must be empha­sized that the gastrointestinal symptoms may be very mild and the patient may present with other manifestations such as anemia [iron or folate de­ficiency), a bleeding diathesis (vitamin K defi­ciency), or metabolic bone disease (vitamin D or calcium deficiency).
Diagnosis. Patients with sprue usually exhibit fat malabsorption, an abnormal xylose test, and an abnormal pattern of dilated intestinal loops with thickened mucosal folds and flocculation of barium on radiographic examination. The Schill­ing test is usually normal but may be abnormal if the disorder extends to the ileum. Peroral biopsy shows the characteristic but not pathognomonic lesion. Finally, and most importantly, there is a clinical and histological response to a gluten-free diet.

Treatment and Prognosis. Treatment is by life­long adherence to a gluten-free diet. Corn flour and rice products can safely be substituted for wheat, barley, and oats. A clinical response usu­ally begins within a few weeks and the patient may continue to improve over a number of months. Reversion to a regular diet usually leads to a rapid return of symptoms. The long-term prognosis is excellent, although patients with ce­liac sprue appear to have a higher incidence of nonHodgkin’s lymphoma in later life.
Bacterial Overgrowth Syndrome. The small intestine usually harbors very few microorga­nisms (<104 colonies per ml). This comparatively sterile sanctuary is thought to result from the com­bined effects of gastric acidity, the rapid sweeping action of normal intestinal motility, and the se­cretion into the intestine of immunoglobulins. When bacteria are present in increased numbers in the small intestine, malabsorption is a frequent consequence. Loss of the normal sweeping func­tion of the gut due to motility disorders or to "blind loops" (e.g., spontaneous or surgically cre­ated diverticula) is the most common cause of upper intestinal bacterial overgrowth.

Pathogenesis. As noted previously the malabsorption associated with bacterial overgrowth may result from three mechanisms: (a) deconju-gation of bile salts, leading to impaired micelle formation; (b) a patchy injury to mucosal cells thought to be due to direct injury by bacteria or bacterial products; and (c) direct utilization of nu­trients by bacteria, best established for vitamin
Conditions Associated with Bacterial Over, growth. A large number of disorders may be as­sociated with bacterial overgrowth. In addition to such gross structural derangements as blind loops, fistulas, or strictures, this syndrome may be found in the impaired intestinal motility of sys­temic sclerosis, amyloidosis, diabetes mellitus, and chronic pseudo-obstruction. It may also occur in hypogammaglobulinemia and in pancreatic in­sufficiency.

Diagnosis. The initial approach to a patient with malabsorption of any cause has been described above and in Figure 36-2. If bacterial overgrowth is suspected based on anatomical abnormalities or on the finding of an abnormal xylose test in the presence of a normal jejunal biopsy, this can be confirmed in one of several ways: (a) by an ab­normal bile acid breath test (if there is no ileal disease), (b) by a positive three-stage Schilling test, (c) by direct culture of jejunal fluid (usually >107 organisms/ml with a mixed culture of an­aerobes for significant bacterial overgrowth), or (d) more simply by a 10- to 14-day therapeutic trial using a broad-spectrum antibiotic.

Treatment. The treatment depends upon the an­atomical and functional cause of the impaired sweeping function of the intestine. Sometimes surgery is indicated. More often patients will re­quire chronic or intermittent antibiotic therapy on an indefinite basis. The most frequently used agents are tetracycline, ampicillin, and trimeth­oprim-sulfamethoxazole. In some forms of mal­absorption, parenteral nutrition may be required. This form of therapy will not be described in this introductory textbook.