|
|
|
The primary function of the gastrointestinal tract is the absorption of fluid and nutrients. Failure of this absorptive process is generally referred to as malabsorption. Malabsorption is most commonly caused by dysfunction in the upper gastrointestinal tract. It can be generalized and affect all nutrients, or it can be specific, involving a single substance.
Evaluation of malabsorption relies heavily on an understanding of normal physiology. In this article, most attention is given to fat malabsorption, or steatorrhea. This is because the methods of detecting increased fecal fat are relatively simple, and colonic bacteria metabolize only a very small fraction of unabsorbed fat during its transit through the colon. Although malabsorption of carbohydrate and protein can occur in the adult patient, with the exception of lactose intolerance, these disorders are much more likely to present in childhood.
After ingestion, proteins are emulsified in the mouth and in the stomach and digested by gastric and pancreatic proteases and peptidases. The products of digestion that are delivered to the small bowel for absorption are free amino acids and small peptides. Because of the ability of the intestinal mucosa to absorb incompletely digested peptides, it is very unusual to observe protein malabsorption in the absence of fat and/or carbohydrate malabsorption. The peptides are absorbed and further broken down in the enterocyte into free amino acids and together with the absorbed amino acids are delivered into the portal vein.
Enzymatic deficiencies in protein digestion can occur in
Carbohydrates are ingested primarily as disaccharides and polysaccharides. Digestion begins with salivary amylase, and intestinal carbohydrases break down more complex polysaccharides into mono- and disaccharides. Associated with the intestinal mucosa are multiple disaccharidases (sucrase, lactase, isomaltase, maltase), which break down the disaccharides into monosaccharides. The monosaccharides are then absorbed by a large variety of monosaccharide transport proteins and passed without alteration into the portal vein.
Because of the abundance of disaccharides in the diet, malabsorption of carbohydrate is generally caused by a deficiency of one of the mucosal disaccharidases. Although deficiencies in one of the other disaccharidases are occasionally seen in the neonatal and pediatric population, lactase deficiency is by far the most common in both pediatric and adult populations. Lactase deficiency can be either congenital or acquired; acquired lactase deficiency can occur after a viral gastroenteritis as well as with normal aging if lactose (milk sugar) is only rarely consumed. Deficiency of lactase causes lactose to pass unabsorbed into the colon, where the osmotic load of the lactose and its breakdown products cause an osmotic diarrhea.
Triglycerides, the major chemical constituent of animal fat and vegetable oil, are an important caloric source, accounting for 36% of calories in the typical American diet. Fat contains 9 calories per gram and as such it is a concentrated caloric source.
The evaluation of fat malabsorption is based on knowledge of the normal physiology of fat absorption and upon evaluation of potential defects in one of the steps involved in normal fat absorption. The treatment of malabsorption is then generally aimed at correction of the underlying defect.
The initial step in fat absorption is the emulsification of dietary fat (Figure 1) . This initially occurs by mastication, followed by gastric mixing. The gastric contractions move material toward an initially closed pylorus, with a resultant retrograde current of gastric contents. This movement creates a shearing action, which helps emulsify the fat, with the emulsified fat generally being stabilized by other dietary constituents. Within the small intestine, peristalsis continues to assist in fat emulsification, although in the small intestine, bile is the usual stabilizing agent. The end result of this emulsification is an increase in the surface area of the fatty constituents of the diet that can be exposed to luminal contents, and thus there is an increase in the amount of lipolysis that can take place. Lipolysis is also initiated in the stomach to a small but significant degree by gastric lipase.
Figure 132-1 Normal physiology
of fat absorption. (1) Emulsification; (2) stimulation of cholecystokinin
release; (3) stimulation of bile and pancreatic enzyme release; (4) pancreatic
lipolysis; (5) micellar solubilization by bile acids; (6) mucosal uptake of
mixed micelles; (7) triglyceride resynthesis; (8) chylomicron formation; (9)
lymphatic transport.
The next step in fat absorption occurs when fatty acids (as well as amino acids and peptides) enter the duodenum. As fat enters the duodenum, cholecystokinin is released.
Cholecystokinin in turn stimulates gallbladder contraction and pancreatic secretion. It also causes relaxation of the sphincter of Oddi. As a result, bile is discharged into the duodenum. Cholecystokinin also induces the discharge of zymogen granules into the pancreatic acini. These pancreatic enzymes and proenzymes then enter the duodenum, where the proenzymes are activated by enzyme enterokinase (located on the surface of intestinal enterocytes). The active enzymes then hydrolyze dietary fat, releasing more fatty acids, which in turn provide positive feedback as the increasing concentration of fatty acids in the intestinal lumen stimulates the release of more cholecystokinin.
Breakdown of triglycerides into fatty acids is essential for micelle formation and fat absorption. Although a small amount of lipolysis occurs in the stomach, pancreatic lipase is responsible for the vast majority of hydrolysis of dietary triglyceride. Pancreatic lipase is secreted by the pancreas in its active form and has both hydrophilic and hydrophobic portions. It binds to the lipid-water interface, where it hydrolyzes triglycerides. The enzyme does have positional specificity and attacks only the alpha ester bonds, generating two fatty acids and one monoglyceride from each triglyceride
The products of lipolysis, free fatty acids and monoglycerides, are insoluble in water. This problem is overcome by the formation of bile acid micelles, which requires a bile acid concentration of greater than 2 mM, the critical micellar concentration. Micellar dispersion increases the concentration of lipolytic products in the aqueous phase approximately 1000-fold.
Bile acids are synthesized by the liver from cholesterol and conjugated with glycine or taurine and stored in the gallbladder. Upon release, they form solubilized lipolytic products for efficient absorption in the jejunum. As they continue to pass down the small intestine, they are actively absorbed in the ileum and returned to the liver via the portal vein; they are then taken up and re-excreted into the bile. This cycle, referred to as enterohepatic circulation of bile acids, represents an extremely efficient reuse of bile acids, as more than 95% are absorbed in the intestine.
After micellar dispersion of lipolytic products by bile salts, diffusion to the cell membrane occurs. A fatty acid-binding protein then assists in the passive diffusion of the micellar lipid into the enterocyte.
Triglycerides are then resynthesized within the cell by the joining of a monoglyceride with two fatty acid-CoA molecules.
Chylomicrons are formed to carry the resynthesized triglycerides in an aqueous-soluble form. A lipoprotein coat is formed around the lipid droplets, and they are extruded through the basolateral membrane of the enterocyte.
Chylomicrons are carried by the lymphatics to the thoracic duct and then into the systemic circulation.
A defect in any of the steps required for proper fat absorption can result in steatorrhea. Loss of emulsification, as with surgical gastrectomy, can be a contributory factor. In addition, a duodenal bypass is part of many gastric ulcer surgeries (e.g., Bilroth II gastrojejunostomy or a Roux-en-Y gastrojejunostomy), resulting in decreased pancreatic and biliary secretion of bile acids and lipase. This reduced secretion can play a role in postgastrectomy malabsorption.
Any form of exocrine pancreatic insufficiency can cause steatorrhea if pancreatic lipase concentration falls to a low enough level. In addition to decreased production, diminished lipase function can occur at a low duodenal pH, as can occur in gastric acid hypersecretory states.
Liver and biliary diseases that cause decreased bile acid secretion can interfere with micellar solubilization of lipids. If the intestinal lumen has a low pH, bile salts can precipitate and micellar solubilization will not occur. Bile acids can also be deconjugated by bacterial overgrowth in the small intestine, and any disruption in the enterohepatic circulation (such as by ileectomy or problems with bile excretion) can result in a deficiency of bile acids being delivered to the intestine. Although the liver can compensate for interference in the enterohepatic circulation to a certain extent, that capacity is limited.
Mucosal uptake of solubilized lipid is impaired in a variety of diseases in which the intestinal mucosa is damaged. Although there is no known defect in the resynthesis of triglycerides after absorption, failure of packaging and lymphatic transport does occur. Failure to synthesize the protein coat of chylomicrons occurs in abetalipoproteinemia, and any disruption of lymphatic transport, whether congenital or acquired, will interfere with transport of lipid from the intestine and likewise result in steatorrhea.
The clinical manifestations of fat malabsorption are associated with steatorrhea (Figure 2) . Typically, the stool is malodorous and large in quantity. There may be an oily sheen on the surface of the water in the toilet. The stool may tend to float (although this commonly occurs with air in the stool as well) and is typically difficult to flush, tending to stick to the porcelain surface of the toilet. Weight loss and abdominal cramping are also frequent complaints.
Physical findings suggestive of fat malabsorption tend to be nonspecific. Weight loss may be clinically apparent but is frequently absent. As fat malabsorption often causes deficiencies in vitamins A, D, E, or K, ecchymoses may be present because of an elevated prothrombin time. The patient may have night blindness secondary to vitamin A deficiency or may present with osteoporosis from calcium malabsorption (vitamin D deficiency). There may be peripheral edema from hypoalbuminemia.
Without evidence pointing toward one single cause of steatorrhea, a relatively simple algorithm can be followed (see Figure 2) . The first step in any evaluation of fat malabsorption is to confirm that steatorrhea is indeed present. A quick screening test is a Sudan stain of a single stool specimen (generally ordered as a ""spot"" or ""qualitative"" fecal fat study); the presence of large globules of fat is strongly suggestive. This can be confirmed by obtaining a 48- or 72-hour fecal fat study. For this, the patient is placed on a high-fat diet (100 grams fat per day), and stool is collected in a 1-gallon paint can (supplied by the laboratory) for 48 or (preferably) 72 hours. A ""typical"" American diet contains approximately 100 grams of fat per day; patients in whom dietary intake is substantially decreased can take a high-fat supplement such as Pulmocare to ensure an adequate fat intake for this study. More than 7 grams of fat in the stool per 24-hour period is considered abnormal. This study has the advantage of quantifying both the degree of fat malabsorption and total stool output. The degree of fat malabsorption may be a useful indicator of the cause of the malabsorption; pancreatic insufficiency tends to have a higher degree of malabsorption then does an intestinal mucosal defect. If the 72-hour fecal fat study does not reveal steatorrhea, then the quantification of total stool output is useful for the evaluation of other nonmalabsorptive causes of diarrhea.
Once steatorrhea has been confirmed, a review of the patient s medical and surgical history is useful. Has the patient undergone gastric or intestinal surgery that may
Figure 132-2 Suggested algorithm for the evaluation of fat malabsorption. The algorithm is
primarily intended for situations in which the cause of the fat malabsorption
is not immediately clinically apparent.
Unless the history suggests a likely cause of malabsorption, the first step is to determine whether the malabsorption is due to a problem in digesting the lipid (i.e., an intraluminal disorder) or to a defect in mucosal uptake and removal. This usually involves evaluation of mucosal function and/or integrity. This is easily accomplished with a small bowel series, which can provide clues as to the diagnosis of a mucosal dysfunction (such as Crohn s disease) or to a predisposition for other causes of the steatorrhea (such as the presence of large jejunal diverticula, which may predispose to bacterial overgrowth, or pancreatic calcifications, which are associated with chronic pancreatitis).
The D-xylose test is a simple and rapid method of assessing mucosal integrity. Twenty-five grams of D-xylose are ingested, and under normal conditions, approximately 50% is absorbed in the small intestine. Of the 50% absorbed, approximately half is metabolized by the liver, with the remaining amount being excreted unchanged by the kidney. Urine is collected for 5 hours after the oral ingestion of the D-xylose and the amount excreted quantified. If 5 grams or more of the D-xylose appears in the urine, mucosal absorption is most likely intact.
The D-xylose test is limited in its specificity for mucosal disease. A decrease in the glomerular filtration rate of the kidney can decrease the amount of D-xylose in urine, as can significant third-space fluid (as in ascites or anasarca), bacterial overgrowth in the small intestine, unusually rapid transit through the small intestine, or incomplete collection of urine by the patient. Hepatic decompensation can result in a falsely elevated level of D-xylose in the urine.
If the small bowel series and D-xylose study are both unremarkable, the most likely cause of steatorrhea is pancreatic insufficiency. A useful study for pancreatic insufficiency is the noninvasive bentiromide test in which an analog of para-amino benzoic acid (PABA), which is rapidly absorbed in the intestine, conjugated in the liver, and excreted in the urine, is photometrically measured in a 6-hour urine sample. PABA is provided bound to an N-benzoyl- L-tyrosyl group (bentiromide), in a 500-mg oral dose. The active pancreatic enzyme chymotrypsin is necessary to free the PABA, which is then rapidly absorbed and excreted. A low urinary level of PABA is strongly suggestive of pancreatic exocrine insufficiency (in the absence of liver disease).
The utility of this test has been severely hampered in recent years by the inconsistent availability of bentiromide. A reasonable alternative is a therapeutic trial of pancreatic enzyme replacements. The enzymes must be given in sufficient amount (a minimum of 20,000 to 40,000 units of lipase (one or two Pancrease MT-20 capsules)) before each meal, and the clinical response to enzyme replacement monitored. Although a symptomatic response
Bacterial overgrowth is suspected when there are suggestive radiographic findings (e.g., jejunal diverticula, a blind intestinal loop, or other functional intestinal defect), or when the D-xylose test is abnormal but the small bowel series and/or mucosal biopsies are normal. The best readily available diagnostic test for bacterial overgrowth of the small intestine is the breath hydrogen test. A 50- to 80-gram dose of glucose is consumed, and serial measurements of breath hydrogen are made (the patient exhales into a bag at fixed intervals). An early rise in exhaled hydrogen concentration suggests bacterial overgrowth. An alternative method is a therapeutic trial of antibiotics and observation for clinical response. Typically, metronidazole (Flagyl), tetracycline, or trimethoprim-sulfamethoxazole (TMP-SMX, Bactrim) is used in standard therapeutic doses. A clinical response should be observed within 1 week.
Endoscopic small bowel biopsies are easily obtained and can provide valuable clues to the cause of steatorrhea in patients in whom the evaluation has suggested a disorder of mucosal function. The small bowel biopsy can occasionally be diagnostic but is more often suggestive. Nonspecific or normal biopsies make it likely that the studies suggesting mucosal disease were misleading and that the diagnosis is more likely pancreatic insufficiency, bile salt deficiency, or small intestinal bacterial overgrowth.
Diagnostic small bowel biopsies can be obtained in Whipple s disease. These tissue specimens have PAS-positive (and AFB-negative) macrophages in the lamina propria. In addition to steatorrhea, polyarticular arthritis, lymphadenopathy, and neurologic problems (from concurrent central nervous system infection) are usually present.
Other mucosal infections can also be diagnosed by biopsy. Steatorrhea is often the sole presenting sign in giardiasis. The beaver is the natural reservoir for Giardia lamblia, so a recent history of camping or consumption of water of unproven potability is common. Some outbreaks have been reported in municipal water systems as well; it can take a year or more for the water system to be purged of Giardia. In immunosuppressed patients, cryptosporidia, mycobacteria, and cytomegalovirus can be seen; these organisms are also occasionally found in patients without other clinical evidence of immunosuppression.
Diagnostic intestinal biopsies can also be obtained in noninfectious mucosal abnormalities. Abetalipoproteinemia is caused by a defect in the packaging of chylomicrons. Intestinal lymphangectasia occurs when the flow of chyle from the intestine is obstructed, and can be congenital, caused by trauma (disruption of the thoracic duct), or associated with medical illnesses (severe pancreatitis). Amyloidosis can also be diagnosed by intestinal biopsy, although rectal biopsies are more commonly performed if this diagnosis is suspected (e.g., in myeloma or connective tissue disorders).
The majority of mucosal biopsies, however, are more likely to be suggestive rather than diagnostic in and of themselves. In celiac disease (nontropical sprue, gluten-sensitive enteropathy) the small bowel biopsy reveals a flattened mucosal surface, villus blunting, elongated crypts, and an inflammatory infiltrate of the lamina propria with a predominance of lymphocytes and plasma cells. Gliadin, a component of the wheat protein gluten, appears to be the causative agent of celiac disease. The diagnosis of celiac disease is made after dietary modification (gluten-free diet) and demonstration of improvement of villus architecture by repeat endoscopic mucosal biopsies.
Mucosal biopsies can also suggest the diagnosis in tropical sprue (similar biopsy appearance to celiac sprue but with a history of travel to tropical areas). Eosinophilic gastroenteritis is suggested by the presence of eosinophils in unusual amounts in the mucosa. The presence of mucosal ulceration or noncaseating granulomata raises the suspicion of Crohn s disease. Granulomata can also be seen in intestinal sarcoid. Intestinal tuberculosis is unlikely to be present unless pulmonary tuberculosis is clinically apparent.
There are many clinical situations in which a full malabsorption evaluation may not be necessary, even in the presence of significant steatorrhea. A patient with known chronic pancreatitis, for example, who presents with foul-smelling, oily stools is very likely to have pancreatic insufficiency. In this situation, it would be reasonable to start pancreatic enzyme replacement without further evaluation and pursue evaluation only if there is no appropriate clinical response. Likewise, the clinical manifestations and laboratory or radiologic studies may suggest a cause of the malabsorption prior to the initiation of a full evaluation. In these situations, it is reasonable to evaluate the most likely cause of the malabsorption first, and if the presumptive diagnosis appears to be correct, treat appropriately and observe for a reduction in steatorrhea. If the expected reduction does not occur, then a more complete evaluation for steatorrhea is certainly warranted.
There is an essential requirement for exogenous protein in order to avoid protein deficiency in all parts of the body. During illness, nitrogen (and protein) loss is exacerbated and intake requirements tend to be higher. The normal adult requires approximately 1 gram of protein per kilogram body weight per day. If an adequate intestinal mucosa is present, it is generally possible to attain protein needs with an oral diet, but some patients may need high-protein supplements.
If protein malabsorption is due to pancreatic enzyme deficiency, these peptidases can be easily replaced with virtually any of the pancreatic enzyme supplements. An inadequately functioning mucosa is much more difficult to manage, however, as the uptake of amino acids and peptides is dependent on transport proteins that are an integral part of the mucosa. If significant mucosal inflammation is present, it can often be decreased with a variety of anti-inflammatory agents, such as aminosalicylates or steroids. In some situations, especially when there is inadequate functioning mucosa because of surgical removal (short bowel syndrome), it may be necessary to provide protein in the form of parenteral amino acids.
As most carbohydrate malabsorption syndromes occur because of a deficiency of an individual disaccharidase, the mainstay of treatment is to eliminate problematic disaccharide from the diet. By far the most common disaccharidase deficiency is of lactase. If dairy products and other rich sources of lactose (regular chewing gum, many presweetened cereals) are avoided, the patient tends to do quite well. As the disaccharidases work within the intestinal lumen, enzyme replacements can be provided orally. There are several commercially available lactase supplements (e.g., Lactaid), which, when taken before ingestion of lactose-containing foods, can ameliorate the malabsorption associated with the native enzyme deficiency.
It is not uncommon for a transient lactase deficiency to develop after an episode of viral gastroenteritis. This is treated by avoiding dairy products for a few weeks, after which they may slowly be reintroduced. As lactase is an inducible enzyme, once the brush border of the intestine is re-established, the enzyme will slowly return to its previously normal levels.
Treatment of fat malabsorption is primarily based on the underlying cause of the malabsorption, which is why determination of the defective step in fat absorption is of importance. A defect in any of the steps required for proper fat absorption can result in steatorrhea.
Defects in fat emulsification occur most commonly after surgical gastrectomy. In this situation, an inadequate amount of surface area of the lipid is exposed for lipolysis and micelle formation. The main treatment for this condition is to limit dietary fat intake or to alter the lipid ratio toward shorter-chain fatty acids; the assistance of a registered dietitian may be useful for dietary instruction.
Other surgical interventions in the upper gastrointestinal tract may also have adverse effects on the stimulation of bile and pancreatic enzyme release. As mentioned, most gastric ulcer surgeries (Bilroth II gastrojejunostomy or Roux-en-Y gastrojejunostomy) bypass the duodenum and thus decrease pancreatic and biliary secretion of bile acids and lipase. Although the flow of bile and pancreatic secretions is maintained, pancreatic enzyme supplementation may be necessary.
Any significant decrease in exocrine pancreatic function can lead to a defect in pancreatic lipolysis. The primary treatment for pancreatic insufficiency is oral pancreatic enzyme replacement. The degree of pancreatic insufficiency is highly variable, and dose titration for pancreatic enzymes is necessary. Most pancreatic enzyme preparations are labeled according to the lipase content, with the more recent formulations containing 5, 10, or 20 thousand international units of lipase (e.g., Creon 10 and Pancrease MT10 both contain 10,000 IU lipase). To avoid fat malabsorption after a typical meal, approximately 28,000 IU active lipase must be in the duodenum during the 4-hour postprandial period. The amount that the patient is supplying from the pancreas cannot be easily measured. In addition, given that substantial amounts of lipase can be degraded by acid pepsin in the stomach, it is clear that inadequate supplementation is a frequent problem. Pancreatic enzyme replacement should start at 10,000 to 20,000 IU lipase at a minimum, and increase from there. Occasionally, the requirement for pancreatic enzyme replacement is lower in borderline cases of steatorrhea. Although histamine-2 receptor antagonists (Tagamet, Zantac, Pepcid, Axid) are often given with pancreatic enzymes, there does not appear to be any advantage to further acid suppression with proton pump inhibitors (Prilosec, Prevacid). In gastric acid hypersecretory states, however, even high doses of lipase can be degraded, and more aggressive gastric acid suppression may be required.
Liver and biliary diseases that cause a decrease in bile acid secretion can interfere with micellar solubilization of lipids. Disruption of the enterohepatic circulation by significant (usually greater than 100 cm) ileectomy can result in a deficiency of bile acids being delivered to the intestine. Although the liver can compensate for interference in the hepatic circulation to a certain extent, that capacity is limited. The steatorrhea from disruption of enterohepatic circulation is controlled by limiting fat intake or by correcting the interruption. Biliary obstruction caused by malignancy of the pancreas or bile duct (cholangiocarcinoma) can often be alleviated by endoscopic stent placement. Use of the bile salt-binding agent cholestyramine can also cause a relative deficiency of bile salts, but this is reversible by lowering the dose of the cholestyramine or discontinuing it altogether.
Bile acids can also be deconjugated by bacterial overgrowth in the small intestine. Bacterial overgrowth is treated with metronidazole (Flagyl), tetracycline, or TMP-SMX in standard therapeutic doses. Clinical response is usually rapid. Given that there is often an anatomic defect that allows the bacterial overgrowth, retreatment is frequently required, often with rotation of the antibiotics used.
Mucosal uptake of solubilized lipid is impaired in a number of diseases in which the intestinal mucosa is damaged. The prototypical mucosal disorder is celiac disease (also called celiac sprue, gluten-sensitive enteropathy, and nontropical sprue). Strict adherence to a gluten-free diet is the most effective therapy for celiac disease, although the diet may be difficult to maintain because it requires avoidance of not only wheat, but also barley and rye cereals and flour. Rice, soybean, and corn flours do not induce celiac disease. This is a disease in which early referral to a registered dietitian is beneficial; unfortunately, insurance coverage for this is spotty. No patient with a biopsy suggestive for celiac disease should be labeled a diet failure without a thorough dietary review. There are some patients who are refractory to dietary treatment;
The diagnosis of tropical sprue is likewise suggested by biopsies that have villus blunting and inflammation very similar to that seen with nontropical (celiac) sprue. This disease occurs primarily (but not universally) in adults who have lived in tropical regions for a year or more, most commonly India, southeast Asia, and the Caribbean. Treatment involves pharmacologic replacement of vitamins and antibiotic treatment of the contaminating coliform bacteria that are thought to cause the disease. Specifically, folate, 5 mg orally (PO) every day with parenteral vitamin B12 , 1000 mug every week, along with tetracycline, 250 mg PO four times a day, is curative in patients who have returned to a temperate climate. Treatment should be given for at least 2 months and can be needed for as long as 6 months, until the intestinal abnormalities disappear. Recurrence has been reported only in those who have returned to the tropical region where the disease was acquired.
The etiology of eosinophilic gastroenteritis has not been determined. In young children, sensitivity to milk is not uncommon, but in other populations evidence for an immune (allergic) pathogenesis is inconclusive and response to dietary elimination is usually disappointing. A stool study for intestinal parasites is warranted, and diagnostic consideration should be given to Crohn s disease and intestinal lymphoma. Effective symptomatic treatment of eosinophilic gastroenteritis is usually obtained with prednisone, 20 to 40 mg PO every day for 7 to 10 days. Retreatment is frequently necessary, and prolonged treatment with steroids is sometimes required. The disease typically waxes and wanes in severity, but the overall prognosis is usually good. Parenteral nutrition is required rarely in patients with refractory disease.
The diagnosis of Crohn s disease, suggested by mucosal ulceration and/or noncaseating granulomata (present in less than half of biopsy tissue), is effectively treated with aminosalicylates, steroids (if more severe), and occasionally immune modifying agents such as azathioprine * (Imuran) or 6-mercaptopurine * (Purinethol). Because active drug is released more proximally in the time-release formulation of the aminosalicylate mesalamine (Pentasa), there are theoretical advantages to using this drug to treat proximal intestinal disease. However, no studies have demonstrated that Pentasa is any more effective for the treatment of proximal intestinal Crohn s than any of the other aminosalicylate preparations (sulfasalazine (Azulfidine), mesalamine (Asacol), olsalazine (Dipentum)).
Whipple s disease, although uncommon, is readily treatable. Identification of the organism is made by genetic analysis (polymerase chain reaction) of biopsy tissue; the organism is resistant to culture. Initial treatment should be with penicillin G (1.2 million units) and streptomycin (1 gram) daily for 10 to 14 days, followed by double-strength TMP-SMX, one tablet PO twice a day for 1 year. Relapses occur in as many as one third of patients but usually respond to repeated twice a day antibiotic therapy.
Infection with Giardia lamblia is treated with metronidazole, 500 mg three times a day for 1 to 2 weeks. Cryptosporidiosis, mycobacterial infection, and cytomegalovirus infection are not uncommon in immunocompromised patients. Cytomegalovirus infection of the intestinal tract is treated with ganciclovir * (Cytovene), 5 mg per kg every 12 hours intravenously or 1000 mg orally three times a day. The duration of treatment is dependent on the cause of immune suppression and whether it can be reversed. If possible, immunosuppression should be lessened (e.g., by decreasing doses of immunosuppressive agents).
Abnormalities in chylomicron formation occur in abetalipoproteinemia. The only effective treatment for this disorder is reduction in dietary lipid consumption. Additionally, pharmacologic replacement of vitamin E (100 mg per kg per day) and supplemental vitamin A and K are given. Likewise, the treatment for defects in lymphatic transport, such as lymphangiectasia, also revolves around dietary fat restriction. If the intestinal lymphangiectasia is secondary (i.e., caused by another disease process blocking the lymphatic drainage of the intestinal tract), then therapy should be aimed at the underlying disease process (e.g., tuberculosis, lymphoma, sarcoidosis, constrictive pericarditis). Malabsorption from congenital lymphangiectasia (Milroy s disease), as well as from secondary lymphangiectasia, is treated by reduction of long chain triglycerides in the diet and substitution with short and medium chain dietary triglycerides. Because of their higher water solubility, the shorter chain fatty acids are more readily absorbed through the portal venous system than through the lymphatics. By manipulating the dietary fatty acid mix to decrease the rate of chylomicron formation, the associated protein-losing enteropathy is generally also decreased.
Finally, steatorrhea can occur from consumption of a nonabsorbable fat product. Olestra (Olean) is a sucrose-lipid polymer that has many of the cooking properties of natural fat but is not absorbed in the human gastrointestinal tract. Olestra s current use is limited to snack foods such as potato chips (fat-free Pringles) or corn chips (Frito Lay MAX chips). Although normal serving sizes of snacks containing olestra are unlikely to cause overt steatorrhea, the likelihood of developing symptoms increases with greater consumption. Because the fat-soluble vitamins can be adsorbed by and excreted with the olestra, vitamins A, D, E, and K are added by federal regulation as a precautionary measure. Avoidance of olestra is curative if symptomatic steatorrhea occurs when consuming this product.
The evaluation and treatment of patients with malabsorption can be intellectually rewarding for the physician. Once the clinical suspicion of malabsorption arises, a careful history, examination, and selective diagnostic evaluation can quickly be performed based upon the knowledge of the normal physiology of absorption. This evaluation almost always leads to establishment of a cause of the malabsorption, which in turn allows initiation of appropriate treatment, and, in the majority of patients, an appreciable clinical response.
|
|
|
"