2. Goals: learning 1. Review of digestion and absorption in GI 2. Disorders of absorption: Celiac disease Tropical sprue Short bowel syndrome Bacterial overgrowth syndrome Whipple’s disease Protein-losing enteropathy

3. Review of digestion and absorption in GI The lengths of the small intestine and colon are ~300 cm and ~80 cm, respectively. However, the effective functional surface area is approximately 600-fold greater than that of a hollow tube as a result of the presence of folds, villi (in the small intestine), and microvilli. The functional surface area of the small intestine is somewhat greater than that of a doubles tennis court. In addition to nutrient digestion and absorption, the intestinal epithelia have several other functions: (1) Barrier and immune defense. (2) Fluid and electrolyte absorption and secretion. (3) Synthesis and secretion of several proteins. The intestinal mucosa is a major site for the production of proteins, including apolipoproteins. Production of several bioactive amines and peptides.

4. Disorders of absorption Celiac Definition Celiac disease is a common cause of malabsorption of one or more nutrients. as high as 1:113 people. Celiac disease has had several other names, including nontropical sprue, celiac sprue, adult celiac disease, and gluten-sensitive enteropathy. The symptoms range from significant malabsorption of multiple nutrients, with diarrhea, steatorrhea, weight loss, and the consequences of nutrient depletion (i.e., anemia and metabolic bone disease), to the absence of any gastrointestinal symptoms but with evidence of the depletion of a single nutrient (e.g., iron or folate deficiency, osteomalacia, edema from protein loss).

5. Disorders of absorption Celiac Etiology Is not known, but environmental (with gliadin, a component of gluten that is present in wheat, barley, and rye), immunologic (Serum antibodies—IgA antigliadin, IgA antiendomysial, and IgA anti-tTG antibodies), and genetic factors (high in whites, low in blacks and Asians, and is 10% in first-degree relatives of celiac disease patients) are important. The onset of symptoms occurring at ages ranging from the first year of life through the eighth decade.

6. Disorders of absorption Celiac Diagnosis A small-intestinal biopsy is required to establish a diagnosis of celiac disease. A biopsy should be performed in patients with symptoms and laboratory findings suggestive of nutrient malabsorption and/or deficiency and with a positive endomysial antibody test. The diagnosis of celiac disease requires the presence of characteristic histologic changes on small-intestinal biopsy together with a prompt clinical and histologic response following the institution of a gluten- free diet.

7. Disorders of absorption Celiac Treatment Gluten-free diet; use of rice in place of wheat flour (More than 90% of patients who have the characteristic findings of celiac disease will respond to complete dietary gluten restriction) The remainder (called refractory celiac disease or refractory sprue) includes some patients who: (1)respond to restriction of other dietary protein, e.g., soy; (2)respond to glucocorticoids; (3)are "temporary" (i.e., the clinical and morphologic findings disappear after several months or years); or (4)fail to respond to all measures and have a fatal outcome, with or without documented complications of celiac disease, such as development of intestinal T cell lymphoma.

10. Disorders of absorption Tropical sprue Definition Tropical sprue is a poorly understood syndrome, and is manifested by chronic diarrhea, steatorrhea, weight loss, and nutritional deficiencies, including those of both folate and cobalamin. This disease affects 5–10% of the population in some tropical areas.

11. Disorders of absorption Tropical sprue Etiology Because tropical sprue responds to antibiotics, the consensus is that it may be caused by one or more infectious agents. Nonetheless, the etiology and pathogenesis of tropical sprue are uncertain.

12. Disorders of absorption Tropical sprue Diagnosis Is best made by the presence of an abnormal small-intestinal mucosal biopsy in an individual with chronic diarrhea and evidence of malabsorption who is either residing or has recently lived in a tropical country. The small-intestinal biopsy in tropical sprue does not have pathognomonic features but resembles, and can often be indistinguishable from, that seen in celiac disease. A gluten-free diet does not result in either clinical or histologic improvement in tropical sprue.

13. Disorders of absorption Tropical sprue Treatment Broad-spectrum antibiotics and folic acid are most often curative, especially if the patient leaves the tropical area and does not return. Tetracycline should be used for up to 6 months and may be associated with improvement within 1–2 weeks.

15. Disorders of absorption Short bowel syndrome Definition This is a descriptive term for the myriad clinical problems that occur following resection of varying lengths of small intestine; or on rare occasions may be congenital, e.g., microvillous inclusion disease.

16. Disorders of absorption Short bowel syndrome Diagnosis In addition to diarrhea and/or steatorrhea, a range of non- intestinal symptoms is also observed in some patients. A significant increase in renal calcium oxalate calculi is observed in patients with a small-intestinal resection with an intact colon and is due to an increase in oxalate absorption by the large intestine, with subsequent hyperoxaluria (called enteric hyperoxaluria).

17. Disorders of absorption Short bowel syndrome Treatment Following resection of the small intestine, the residual intestine undergoes adaptation of both structure and function that may last for up to 6–12 months. Continued intake of dietary nutrients and calories is required to stimulate adaptation via direct contact with intestinal mucosa, the release of one or more intestinal hormones, and pancreatic and biliary secretions. Thus, enteral nutrition with calorie administration must be maintained, especially in the early postoperative period, even if an extensive intestinal resection requiring parenteral nutrition (PN) had been performed. Cholestyramine, an anion-binding resin, and calcium have proved useful in reducing the hyperoxaluria.

18. Disorders of absorption Short bowel syndrome Treatment (continued) Depends on the severity of symptoms and whether the individual is able to maintain caloric and electrolyte balance with oral intake alone. Initial treatment includes judicious use of opiates (including codeine) to reduce stool output and to establish an effective diet. An initial diet should be low-fat and high-carbohydrate, if the colon is in situ, to minimize the diarrhea from fatty acid stimulation of colonic fluid secretion. MCTs, a low-lactose diet, and various soluble fiber-containing diets should also be tried.

19. Disorders of absorption Short bowel syndrome Treatment (continued) The patient's vitamin and mineral status must also be monitored; replacement therapy should be initiated if indicated. Fat-soluble vitamins, folate, cobalamin, calcium, iron, magnesium, and zinc are the most critical factors to monitor on a regular basis. If these approaches are not successful, home PN is an established therapy that can be maintained for many years. Small intestinal transplantation is becoming established as a possible approach for individuals with extensive intestinal resection who cannot be maintained without PN, i.e., "intestinal failure.”

20. Disorders of absorption Bacterial overgrowth syndrome Definition Bacterial overgrowth syndrome comprises a group of disorders with diarrhea, steatorrhea, and macrocytic anemia whose common feature is the proliferation of colonic-type bacteria within the small intestine. This bacterial proliferation is due to stasis caused by impaired peristalsis (functional stasis), changes in intestinal anatomy (anatomic stasis), or direct communication between the small and large intestine. These conditions have also been referred to as stagnant bowel syndrome or blind loop syndrome.

21. Disorders of absorption Bacterial overgrowth syndrome Etiology Is bacterial proliferation in the small intestinal lumen secondary to either anatomic or functional stasis or to a communication between the relatively sterile small intestine and the colon with its high levels of aerobic and anaerobic bacteria. Several examples of anatomic stasis have been identified: (1)One or more diverticula (both duodenal and jejunal); (2)Fistulas and strictures related to Crohn's disease ; (3)A proximal duodenal afferent loop following a subtotal gastrectomy and gastrojejunostomy; (4)A bypass of the intestine, e.g., jejunoileal bypass for obesity; (5)Dilation at the site of a previous intestinal anastomosis.

22. Disorders of absorption Bacterial Overgrowth Syndrome Treatment Bacterial overgrowth secondary to strictures, one or more diverticula, or a proximal afferent loop can potentially be cured by surgical correction of the anatomic state. In contrast, the functional stasis of scleroderma or certain anatomic stasis states (e.g., multiple jejunal diverticula) cannot be corrected surgically, and these conditions should be treated with broad-spectrum antibiotics. Tetracycline used to be the initial treatment of choice; due to increasing resistance, however, other antibiotics such as metronidazole, amoxicillin/clavulanic acid, and cephalosporins have been employed. The antibiotic should be given for approximately 3 weeks or until symptoms remit.

23. Disorders of absorption Whipple’s disease Definition Whipple's disease is a chronic multisystem disease associated with diarrhea, steatorrhea, weight loss, arthralgia, and central nervous system (CNS) and cardiac problems; it is caused by the bacteria Tropheryma Whipplei. The onset of Whipple's disease is insidious and is characterized by diarrhea, steatorrhea, abdominal pain, weight loss, migratory large-joint arthropathy, and fever as well as ophthalmologic and CNS symptoms. The development of dementia is a relatively late symptom and an extremely poor prognostic sign, especially in patients who relapse following the induction of a remission with antibiotics.

24. Disorders of absorption Whipple’s disease Treatment Is prolonged use of antibiotics. The current drug of choice is double-strength trimethoprim/sulfamethoxazole for approximately 1 year. If trimethoprim/sulfamethoxazole is not tolerated, chloramphenicol is an appropriate second choice.

25. Disorders of absorption Protein-losing enteropathy Definition A group of gastrointestinal and nongastrointestinal disorders with hypoproteinemia and edema in the absence of either proteinuria or defects in protein synthesis such as chronic liver disease. These diseases are characterized by excess protein loss into the gastrointestinal tract.

26. Disorders of absorption Protein-losing enteropathy Diagnosis The diagnosis of protein-losing enteropathy is suggested by the presence of peripheral edema and low serum albumin and globulin levels in the absence of renal and hepatic disease.

27. Disorders of absorption Protein-losing enteropathy Treatment Should be directed primarily to the underlying disease process and not to the hypoproteinemia. For example, if significant hypoproteinemia with resulting peripheral edema is secondary to either celiac disease or ulcerative colitis, a gluten-free diet or mesalamine, respectively, would be the initial therapy. When enhanced protein loss is secondary to lymphatic obstruction, it is critical to establish the nature of this obstruction. Treatment of the hypoproteinemia is accomplished by a low-fat diet and the administration of MCTs.