- Email: [email protected]
Malabsorption Syndromes: Nutritional Management
MALABSORPTION SYNDROMES
Nutritional Management PM Tsai, University of California, San Francisco, CA, USA C Duggan, Harvard Medical School, Boston, MA, USA r 2013 Elsevier Ltd. All rights reserved.
Glossary Anthropometrics Body measurements used to determine body fat composition. Bioelectrical impedance A method that uses a small electrical current to measure body composition. DEXA scan A dual energy X-ray absorptiometry scan that uses X-ray beams to measure bone density and/or body composition.
Introduction The human gastrointestinal tract has an impressive capacitance for water, electrolyte, and nutrient absorption. In some disease states, however, this excess capacity is outpaced by either intestinal secretion or inadequate absorption. Malabsorption is defined as the inability of the gastrointestinal tract to adequately absorb nutrients. Although strictly speaking, malabsorption is distinct and contrasted with maldigestion (inadequate breakdown of nutrients in the intestinal lumen); the therapeutic implications of these two conditions are often similar. Multiple causes of malabsorption exist and reviews of these individual diagnoses can be found in separate sections of this text (e.g., inflammatory bowel disease, cystic fibrosis, short bowel syndrome, etc.). The pathophysiology, symptoms, and nutritional therapies for common malabsorption syndromes have been reviewed.
Pathophysiology and Symptoms Malabsorption can occur when any of the several steps in nutrient digestion, absorption, and/or assimilation are interrupted; see Table 1 for a list of congenital defects in nutrient assimilation. Carbohydrate malabsorption can occur, for instance, when intestinal disaccharidases are reduced in concentration at the enterocyte. The brush border membrane produces four disaccharidases that are important in carbohydrate digestion. These enzymes are sucrase-isomaltase, maltase-glucoamylase, trehalase, and lactase-phlorizin hydrolase. Worldwide, lactase deficiency is the most common type of acquired disaccharidase deficiency. With lactase deficiency, malabsorbed carbohydrate remains in the intestinal lumen and exerts an osmotic pull on fluids and electrolytes, leading
136
Endoscopy A procedure that uses an instrument to look inside the body for diagnostic or therapeutic purposes. Protein hydrolysate A type of formula in which proteins are broken down into smaller peptides by hydrolysis.
to abdominal cramping and loose stools. Malabsorbed carbohydrate can be metabolized by gastrointestinal tract bacteria, and the fermented gas produced is associated with flatulence and bloating. Bacterial overgrowth of the small intestine, as seen with short bowel syndrome, can also be associated with carbohydrate malabsorption. Steatorrhea, excessive fat in the stools, results from fat malabsorption or maldigestion and can have several causes, most notably pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, Shwachman-Diamond syndrome, and Johanson-Blizzard syndrome. Failure of pancreatic secretion of lipase, amylase, and other digestive enzymes leads to persistence of dietary fat in the intestinal lumen, causing bloating, abdominal pain, and bulky, foul-smelling, oily stools. The stools often float due to a high gas content and test positive for fat. Patients also complain of blunted appetite and nausea. Other causes of fat malabsorption include hepatobiliary disease with inadequate bile salt circulation, severe mucosal disease, and short bowel syndrome. The most common cause of protein malabsorption is socalled protein-losing enteropathy. Etiologies include diffuse mucosal disease such as celiac disease or Crohn’s disease, elevated right heart pressure with resultant dilatation of lymphatics and leakage of lymph into the lumen, and invasive enteropathies as seen with Shigella or Salmonella infections. Because protein is a relatively minor component of dietary energy compared with carbohydrate and fat, symptoms of protein malabsorption can sometimes be minimal. However, infectious colitis or exacerbations of inflammatory bowel disease often present with frequent loose stools, which may be bloody. Rarely, congenital etiologies of protein malabsorption include enterokinase and trypsinogen deficiencies (Table 1). Finally, the malabsorption of various micronutrients can occur in conjunction with or separate from the macronutrient
Encyclopedia of Human Nutrition, Volume 3
http://dx.doi.org/10.1016/B978-0-12-375083-9.00178-1
Malabsorption Syndromes: Nutritional Management
137
Table 1 Congenital defects in nutrient assimilation. Included are congenital defects that are associated with gastrointestinal symptoms and/or nutritional deficiencies. Congenital defects not included here include multiple defects in amino acid absorption Disorder
Gene/protein affected
Symptoms
Carbohydrate digestion Congenital lactase deficiency Hypolactasia Congenital sucrase-isomaltase deficiency
Lactase Lactase Sucrase-isomaltase
Lactose-induced diarrhea Lactose-induced diarrhea Sucrose-induced diarrhea
Carbohydrate absorption Glucose–galactose malabsorption Fructose malabsorption Fanconi-Bickel syndrome
Sodium-glucose-co-transport (SGLT1); SLC5A1 Facilitative fructose transport (GLUT5); SLC2A5 Facilitative glucose transport (GLUT2); SLC2A2
Glucose-induced diarrhea Fructose-induced diarrhea Diarrhea and nephropathy
Protein digestion Enterokinase deficiency Trypsinogen deficiency
Serine protease 7 Trypsinogen
Diarrhea and edema Diarrhea and edema
Fat digestion Pancreatic lipase deficiency
Pancreatic lipase
Steatorrhea
Microsomal triglyceride transfer protein Apolipoprotein B Sar1-ADP-ribosylation factor family GTPases Sodium-bile acid transporter; SLC10A2 ATP-binding cassette transporter 1 ATP-binding cassette, subfamily G, member 8; ABCG8
Steatorrhea Steatorrhea Steatorrhea Steatorrhea, bile acid diarrhea Hepatosplenomegaly Atherosclerosis
Ion and metal absorption Congenital sodium diarrhea Congenital chloride diarrhea Cystic fibrosis Acrodermatitis enteropathica Menkes disease Primary hypomagnesemia Hemachromatosis
Defective Na þ /H þ exchange Defective Cl /HCO3 exchange CFTR Zinc and iron-regulated transport proteins; SLC39A4 Copper transporter Paracellin 1; claudin 16 Hepcidin, others
Secretory diarrhea Secretory diarrhea Pancreatic insufficiency, meconium ileus Diarrhea and dermatitis Developmental delay Seizures, deafness and polyuria Cirrhosis, cardiomyopathy, diabetes
Vitamin absorption Folate malabsorption
? Intrinsic factor Cubilin, amnionless Transcobalamin II Thiamine transport protein; SLC19A2 Retinol-binding protein 4
Macrocytic anemia, diarrhea, developmental delay Macrocytic anemia, developmental delay Anemia, proteinuria Anemia, diarrhea, developmental delay Anemia, diabetes, cranial nerve defects Ophthalmologic problems
Alpha-tocopherol transport protein
Vitamin E malabsorption
Fat assimilation Abetalipoproteinemia Hypobetalipoproteinemia Chylomicron retention disease Primary bile acid malabsorption Tangier disease Sitosterolemia
Congenital pernicious anemia Imerslund-Graesbeck syndrome Congenital deficit of transcobalamin II Thiamine-responsive megaloblastic anemia Familial retinol binding protein (RBP) deficiency Selective vitamin E deficiency
Source: Adapted from Martin M and Wright EM (2008) Congenital intestinal transport defects. In: Kleinman RE, Goulet O, Mieli-Vergani G, Sanderson IR, Sherman P, and Shneider B (eds.) Walker’s Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 5th edn., p. 290. Hamilton, Ontario: BC Decker.
malabsorption syndromes noted above. For instance, steatorrhea can be accompanied by excessive fecal losses of the fat soluble vitamins A, D, E, and K, as well as calcium and other minerals. Alternatively, atrophic gastritis or surgical resection of the terminal ileum can lead to Vitamin B12 malabsorption in the absence of any symptoms of diarrhea. Proximal bowel resection can result in iron, zinc and calcium malabsorption. A rare cause of micronutrient inadequacy is abetalipoproteinemia in which fat soluble nutrients are normally digested and absorbed by the intestine but are not delivered to the circulation due to defective transepithelial transport. Other rare causes of micronutrient malabsorption are noted in Table 1.
General Nutritional Management of Malabsorption As with all nutritional disorders, a thorough nutritional assessment is needed to plan rational therapy of malabsorption. Important historical points to review include duration of symptoms, underlying etiology of malabsorption, ability to meet nutritional needs by mouth, presence of food allergies, and concurrent medical and surgical problems. The patient’s nutritional status (weight, height, body mass index, and their respective percentiles) should be determined. Tests of body composition such as arm anthropometrics, bioelectrical impedance, or DEXA scan should be considered. If the
138
Malabsorption Syndromes: Nutritional Management
underlying cause of malabsorption is not known, diagnostic gastrointestinal endoscopy, laboratory studies, and/or imaging studies are indicated.
Specific Nutritional Management of Malabsorption Fluids and Electrolytes Diarrhea is usually the most distressing problem for patients with malabsorption and may cause dehydration. Care should be taken to correct fluid losses with appropriately designed oral rehydration solutions. Even in the setting of massive secretory diarrhea such as seen with cholera infections, oral rehydration solutions are effective at treating dehydration. Recent data have supported the safety and efficacy of oral rehydration solutions of reduced osmolarity in children with dehydration from acute diarrhea. An oral rehydration solution with the following composition: glucose 75 mmol l1, sodium 75 mmol l1, potassium 20 mmol l1, base 30 mEq l1, and osmolality 245 mOsm l1 is well-suited for the rehydration and maintenance therapy during dehydration due to diarrhea. In some cases of severe diarrhea, parenteral hydration is the mainstay of therapy. Examples include glucose–galactose malabsorption, congenital chloride diarrhea, microvillous inclusion disease, and tufting enteropathy. These cases, as well as other severe causes of more common malabsorptive syndromes, also frequently require the use of parenteral nutrition therapy.
Carbohydrate Malabsorption Lactose Intolerance Lactose intolerance is defined by the occurrence of symptoms after ingestion of lactose, the main carbohydrate in milk. These symptoms may include abdominal pain, bloating, diarrhea, or flatulence. Lactose intolerance is usually secondary to lactose malabsorption caused by a relative deficiency of the disaccharidase lactase, which reduces the ability to digest lactose. Primary lactase deficiency is a condition in which lactase activity falls after weaning around 2 years of age. Secondary lactose intolerance may be temporary and is usually due to mucosal injury associated with a condition or disease such as infectious diarrhea, Crohn’s disease, or short bowel syndrome. In addition to the presence or absence of the lactase enzyme, other factors determine whether a person will have symptoms of lactose malabsorption, including the amount of lactose in the diet, the mixture of lactose with other foods, gastric emptying rate, colonic scavenge of malabsorbed carbohydrate, ethnic origin and age. Although persons of Northern European ancestry commonly maintain the ability to digest lactose into adulthood, primary lactose intolerance is prevalent in African–American, Hispanic, Native American, and Asian populations. Nutritional management of lactose intolerance consists largely of the removal of lactose from the diet. Lactose is a common ingredient in many foods, including breads, crackers, soups, cereals, cookies, and baked goods. Eliminating or reducing lactose-containing ingredients from one’s diet is
Table 2
Commercial calcium supplements
Product
Manufacturer
Mg Calcium/ tablet
IU vitamin D
Citracal Regular OsCal 500 þ D Tums Calcium Milk Free Cal-citrate þ D Caltrate 600 þ D Viactiva
Bayer GlaxoSmithKline GlaxoSmithKline Nature’s Plus
500 500 500 250
400 200 0 50
Freeda Pfizer McNeil Nutritionals
250 600 500
100 400 500
a
This product contains less than 0.5 mg lactose. Source: Adapted from DiSanto C and Duggan C (2005) Gastrointestinal diseases. In: Hendricks KM and Duggan C (eds.) Manual of Pediatric Nutrition, 4th edn., p. 212. Hamilton, Ontario: BC Decker.
usually adequate to relieve symptoms. Individuals with primary lactose intolerance may require a permanent dietary change. Individuals with secondary lactose intolerance should eliminate all lactose from their diets for a short period of time ranging from 2 to 6 weeks. If symptoms resolve, lactose may be reintroduced slowly as tolerated by the individual. The amount of lactose that an individual can tolerate is highly variable. Many children can tolerate small amounts of lactose, particularly yogurt or hard cheese, without discomfort. Many adults who consider themselves lactose intolerant can actually tolerate moderate amounts of milk. Lactose intolerant individuals may also tolerate small amounts of lactose consumed over the course of the day better than a large dose all at once. For individuals who choose to restrict lactose in their diets, a variety of lactose-free and low-lactose food choices are available. Lactose-reduced products, containing 70–100% less lactose than standard foods, are available commercially. Individuals may also choose to consume dairy products with concomitant administration of lactase enzyme tablets or drops. Frequent consumption of milk and other dairy foods has been associated with better bone health in some studies, and a strict lactose-free diet may not contain adequate amounts of calcium and vitamin D. Table 2 provides a list of some commercially available lactose-free and lactose-reduced calcium supplements.
Sucrose Congenital sucrase-isomaltase deficiency (SID) is the most common congenital disaccharidase deficiency. Patients with this disorder lack functional sucrase, although isomaltase deficiency may be normal or absent. Symptoms of SID can include diarrhea, abdominal pain, and poor weight gain. Dietary avoidance of sucrose or table sugar helps relieve symptoms, and can sometimes help with the diagnosis. Sucraids, a sacrosidase produced from Saccharomyces cerevisiae, is an enzyme that can be given with meals and allows increased tolerance to sucrose.
Fat Malabsorption: Fat and Fat-Soluble Nutrients Patients with pancreatic insufficiency are unable to produce and secrete enough enzymes to aid with the breakdown of fats
Malabsorption Syndromes: Nutritional Management
in the intestinal lumen. In studies of normal adults and those with pancreatic insufficiency, pancreatic enzyme secretion needs to be lower than 15% of normal levels before significant steatorrhea is seen (Figure 1). Once clinically significant steatorrhea is determined, recovery of pancreatic function is therefore unlikely. Historically, patients with pancreatic insufficiency due to cystic fibrosis (CF) were told to minimize symptoms of steatorrhea by limiting dietary fat. However, epidemiologic studies confirmed that this advice lead to negative energy balance, undernutrition, and higher mortality rates, compared to communities in which CF patients were treated with high-energy and high-fat diets. The introduction of effective pancreatic replacement therapy has been heralded as one of the most significant breakthroughs in the nutritional management of CF, responsible partly for the substantial increase in lifespan enjoyed by more recent generations of CF patients. In fact, the finding of a lower incidence of growth failure in CF patients diagnosed and treated with aggressive nutritional therapy early in infancy has been used as justification for neonatal screening of this condition. Judicious use of pancreatic replacement enzymes is the hallmark of nutritional therapy of CF and other disorders of pancreatic insufficiency. Multiple commercial preparations of porcine pancreatic enzymes are available, most of which contain lipase, amylase, and protease enzymes. A nonporcine pancreatic enzyme is currently under development. The dose is usually titrated to the amount of steatorrhea. If meals take more than 30 min, the dose may be divided with half given before the meal and half given mid-way through the meal. Patients who cannot swallow pills may open the capsules and sprinkle the enzymes into acidic foods. Another critical aspect of the nutritional management of fat malabsorption is routine supplementation with the
Fecal fat (gm/24 hr)
100
75
Health EAA ID Pancreatic disease EAA ID CCK-PZ IV
50
25 Upper limit of normal 0
12
25
(<15% of normal)
50
75
100
139
fat-soluble vitamins A, D, E, and K. Multiple studies have confirmed that patients with CF, Crohn’s disease, and other malabsorptive disorders are prone to micronutrient deficiencies, and some literature suggests that dietary needs for these and other antioxidant nutrients may be increased in settings of infectious and catabolic stress often suffered by these patients. The contribution of fat malabsorption contributing to other important mineral malabsorption, as in the case of calcium or zinc, should also be recognized. Routine supplementation of fat-soluble vitamins is indicated in patients with fat malabsorption. In addition, serial measurement of fat-soluble vitamin biochemical status is recommended. Because blood nutrient concentrations of these and other nutrients can vary with the concentration of transport proteins, correction for these can aid the interpretation of these lab findings. For instance, vitamin A toxicity should be suspected if the molar ratio of vitamin A: Retinolbinding protein exceeds 1. Vitamin E concentrations, for example, should be corrected for circulating lipids. Some patients with pancreatic malabsorption may benefit from a diet enriched in medium chain triglycerides (MCTs). MCTs are absorbed directly into the portal circulation and therefore bypass the steps of intraluminal digestion, reesterification, and enterocyte uptake. Therefore, these fats may be a dietary source of fats more easily absorbed in settings of fat malabsorption due to either pancreatic insufficiency or mucosal disease. However, MCT oils are less energy dense than long-chain fats, are more expensive, and do not contain the essential fatty acids alpha-linoleic and linolenic acid.
Protein Malabsorption Protein-losing enteropathy (PLE) can also be treated with a variety of nutritional interventions. PLE due to dilated lymphatics as with right heart failure results in leakage of lymphocytes, proteins, and fats into the intestinal lumen. As with fat malabsorption, MCT-supplemented foods and formulas are therefore indicated to allow improved fat absorption in PLE. Fat-soluble vitamin supplementation is indicated. In congenital protein malabsorption syndromes, peptide- or amino acid-based formulas are often helpful. Mucosal disorders including inflammatory bowel disease, allergic diseases, and celiac disease are other examples of disorders causing protein malabsorption. Once intestinal inflammation is reduced with appropriate medical or nutritional therapy, absorption of protein is usually improved. In Shigella infections, some studies have suggested improved nutritional outcomes with a high-protein diet during recovery from the acute symptoms of diarrhea.
125
Lipase output (kU hr −1)
Figure 1 Pancreatic enzyme secretion and steatorrhea. Significant steatorrhea ensues when pancreatic function is less than 15% of normal. Reproduced with permission from DiMagno EP, Go VLW, and Sumerskill WHJ (1973) Relations between pancreatic enzyme output and malabsorption in severe pancreatic insufficiency. New England Journal of Medicine 288: 814. Copyright r 1973 Massachusetts Medical Society. All rights reserved.
Route of Nutrition in Malabsorption Several factors need to be considered when recommending whether oral, enteral, or parenteral nutrition should be used in providing nutrition to the patient with malabsorption. These factors include etiology of malabsorption, severity of gastrointestinal disease, and underlying nutritional and medical conditions. Oral nutrition using modified diets as noted above is, of course, the most customary and desirable by
140
Malabsorption Syndromes: Nutritional Management
physician and patient alike. In cases of mild lactose malabsorption, for instance, modification of a regular, healthy diet to avoid foods high in lactose should be sufficient. In cases where widespread gastrointestinal disease is leading to severe malabsorption, enteral or ‘tube’ feeding is helpful for two main reasons: (1) use of proprietary formulas specially designed for malabsorption are often indicated, and these formulas may be unpalatable, and (2) enteral feedings, especially with slow continuous ‘drip’ feedings make efficient use of nutrient transport kinetics, thereby maximizing residual gastrointestinal absorptive function. In severe cases of malabsorption in which tube feedings are unable to achieve adequate nutritional intake, parenteral nutrition may be indicated. Emerging data suggest that serum citrulline, an amino acid synthesized principally by the enterocyte, is a reliable biomarker of mucosal mass and may help distinguish among patients who require parenteral versus enteral nutrition.
Selection of Enteral Formulas for Malabsorption A number of commercially available formulas are designed for patients with malabsorption, and these differ with regard to energy density, macronutrient composition, and indicated age. Because infant formulas are often handled in a separate regulatory fashion by governments, infant formulas are usually considered separately from formulas designed for older children and adults. In addition, formulas are also conventionally categorized by the extent of the hydrolysis of their protein source. Categories include intact protein formulas, protein hydrolysate formulas, and amino acid-based formulas. Protein hydrolysate formulas are also sometimes referred to as ‘semielemental’ formulas, and amino-acid formulas are sometimes called ‘elemental’ formulas. However, these terms suffer from vagueness and inaccuracies because not all of their macronutrients are semi or completely elemental. Marketing strategies often compound the confusion with misleading formula names. These terms should be discouraged, and the terms that refer to the composition and/or biochemical processing should be used instead. Patients who have carbohydrate malabsorption from lactose intolerance should use lactose-free formula. Fat malabsorption may call for MCT enriched formula. In cases of protein malabsorption or severe enteropathy, a formula that is a protein hydrolysate or amino acid based would be most appropriate. Because many malabsorption syndromes overlap in terms of the macronutrient affected, as in cases of severe mucosal disease, some formulas are designed for fat, protein, and carbohydrate malabsorption. For example, all formulas designed for use in adults are lactose free, and several formulas contain both hydrolyzed proteins and MCT oils.
Clinical Management of Malabsorption Two of the most clinically challenging scenarios for the management of malabsorption are inflammatory bowel disease (especially Crohn’s disease) and short bowel syndrome. Both are discussed in separate articles of the text, but are considered briefly below.
Inflammatory Bowel Disease Patients with Crohn’s disease have widespread and intermittent gastrointestinal inflammation. Some patients with inflammatory bowel disease may require complete bowel rest for several days or even a few weeks to allow time for mucosal healing. To provide nutrition during this period of time, parenteral nutrition may be needed. Numerous studies have shown that patients with Crohn’s disease may safely and effectively achieve clinical remission with primary nutritional therapy. Early literature in the field highlighted the use of protein hydrolysate formulas, which, due to unpalatability, often required administration via a nasogastric or gastrostomy tube. More recent data have confirmed that intact protein formulas, termed ‘polymeric’ formulas when describing formulas designed for adults, may work as well as protein hydrolysates, and these formulas can be feasibly given by mouth. As patients are recovering from an exacerbation and begin advancing their diet, patients should temporarily minimize the amount of fiber ingested to decrease trauma to healing mucosa. Patients whose disease affects the small intestine often benefit from temporary avoidance of lactose products as the mucosa heals and brush border membrane enzyme production is restored. Micronutrients are also needed in the nutritional management of inflammatory bowel disease. Iron supplementation is recommended for anemia due to acute or chronic blood loss. Treatment of inflammatory bowel disease frequently requires the use of steroids, which affects bone density. Calcium and vitamin D supplementation is commonly needed to minimize the osteopenic effects of steroid therapy and/or the effects of malabsorption and chronic inflammation.
Short Bowel Syndrome Patients who have suffered acquired or congenital loss of small intestinal surface area that makes them dependent on specialized enteral or parenteral support are said to have short bowel syndrome (SBS). Patients with SBS often malabsorb carbohydrates, proteins, fat, as well as numerous micronutrients, depending on the extent and location of bowel resection, as well as the presence of mucosal disease in the nonresected bowel. Special attention should be given to exactly what part of the intestine remains as well as the length of the remaining intestine. Some patients may have the terminal ileum removed and are unable to absorb vitamin B12 and bile acids. Removal of the ileocecal valve increases the risk of bacterial overgrowth. Reduced length also means reduced surface area for the absorption of nutrients and decreased intestinal transit time. In the immediate postoperative period, parenteral nutrition and gut rest should be used because significant stool output is the norm. Output should be quantified, and electrolytes must be carefully monitored in order to determine appropriate replacement fluids to make up for excess urine, stool, and ostomy losses. Replacement fluids should generally be given separately from standard parenteral nutrition so that
Malabsorption Syndromes: Nutritional Management
Table 3
141
Feeding advancement in short bowel syndrome
1. Stool output Ifo10 g kg 1 d 1 or o10 stools d 1 If 10–20 g kg 1 d 1 or 10–12 stools d 1 If420 g kg 1 d 1 or412 stools d 1 or 2. Ileostomy output Ifo2 g kg 1 h 1 If 2–3 g kg 1 h 1 If43 g kg 1 h 1 3. Stool reducing substances Ifo1% If¼1% If41% 4. Signs of dehydration If absent If present 5. Gastric aspirates o four times previous hour’s infusion 4 four times previous hour’s infusion
Advance rate by 10–20 ml kg d 1 no change Reduce rate or hold feedsa Advance rate by 10–20 ml kg 1 d 1 no change Reduce rate or hold feedsa Advance feeds per stool or ostomy output no change Reduce rate or hold feedsa Advance feeds per stool or ostomy output Reduce rate or hold feedsa Advance feeds Reduce rate or hold feedsa
a
Feeds should generally be held for 8 h, then restarted at 3/4 the previous rate. Source: Adapted from Utter SL and Duggan C (2005) Short bowel syndrome. In: Hendricks KM and Duggan C (eds.) Manual of Pediatric Nutrition, 4th edn., pp. 728–729. Hamilton, Ontario: BC Decker.
they can be adjusted as needed to rapid shifts in fluid and electrolyte status. As patients recover from surgery, every attempt should be made to feed them enterally as soon as is feasible. Enteral feeds facilitate growth and adaptation of the remaining bowel to allow partial compensation for the missing portion, and several studies have correlated early feeding with better longterm outcome. Attaining independence from parenteral nutrition may take weeks to months to years. Table 3 outlines an approach to determine feeding advancement in SBS. Although some patients are able to grow well or maintain their body weight with only enteral feeds, many are dependent on parenteral nutrition. Some patients with SBS also have oral feeding aversion due to prematurity, prolonged mechanical ventilation, and/or prolonged orogastric or nasogastric feeding. Gastrostomy tubes are particularly helpful in this regard. In infants, breast milk should be used if available. The breast milk may need to be fortified to increase calories, protein, or fat. For older patients or infants who are not receiving breast milk, protein hydrolysates or amino acid-based formulas may be better tolerated because the residual bowel more easily absorbs these nutrients. Lactose-free and MCTcontaining formulas are often used, as well. Formulas may need to be supplemented with oral rehydration solutions if electrolyte abnormalities persist, particularly with sodium losses through persistent high stool or ostomy output. Because many patients with SBS are dependent on parenteral nutrition for prolonged periods of time, selenium, carnitine, copper, and zinc blood concentrations should be checked periodically and supplemented if needed. Parenteral nutrition should be cycled off for a few hours each day to help simulate more natural cyclic fluctuations of gastrointestinal hormones. These patients also often have poor absorption of calcium and need calcium supplements to prevent osteopenia, which increases the risk of fractures. Iron may also be needed in patients with anemia from decreased absorption secondary to resection of the duodenum or jejunum. Ultimately,
weaning from parenteral and enteral nutrition remain the goals of treatment, though lifelong dietary therapy is often needed.
Summary Congenital or acquired diseases of the gastrointestinal tract can lead to life-threatening malabsorption of numerous macronutrients and micronutrients. Determining the type and etiology of malabsorption is essential to provide appropriate nutritional and medical therapy. Multiple formulas, supplements, and dietary regimens exist to target specific defects in the digestion, absorption, and assimilation of nutrients. In addition, many new nutrients are undergoing investigation that may become a standard part of care in the future, including probiotics, prebiotics, and various amino acids.
See also: Celiac Disease. Cystic Fibrosis. Lactose Intolerance
Further Reading Ce´zard JP (2008) Normal physiology of intestinal digestion and absorption. In: Kleinman RE, Goulet O, Mieli-Vergani G, Sanderson IR, Sherman P, and Shneider B (eds.) Walker’s Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 5th edn., pp. 245–252. Hamilton, Ontario: BC Decker. Crenn P, De Truchis P, and Neveux N (2009) Plasma citrulline is a biomarker of enterocyte mass and an indicator of parenteral nutrition in HIV-infected patients. American Journal of Clinical Nutrition 90(3): 587–594. Holt PR (2007) Intestinal malabsorption in the elderly. Digestive Diseases 25: 144–150. Iannitti T and Palmieri B (2010) Therapeutical use of probiotic formulations in clinical practice. Journal of Clinical Nutrition In press.http://dx.doi.org/10.1016/ j.clnu.2010.05.004. Olieman JF, Penning C, Ijsselstijn H, et al. (2010) Enteral nutrition in children with short-bowel syndrome: Current evidence and recommendations for the clinician. Journal of the American Dietetic Association 110: 420–426.
142
Malabsorption Syndromes: Nutritional Management
Rubio-Tapia A and Murray JA (2010) Celiac disease. Current Opinion in Gastroenterology 26: 116–122. Shikhare G and Kugathasan S (2010) Inflammatory bowel disease in children: Current trends. Journal of Gastroenterology 45: 673–682. Stallings VA, Stark LJ, Robinson KA, et al. (2008) Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: Results of a systematic review. Journal of the American Dietetic Association 108: 832–839. Treem WR, McAdams L, Stanford L, et al. (1999) Sacrosidase therapy for congenital sucrase-isomaltase deficiency. Journal of Pediatric Gastroenterology and Nutrition 28: 137–142.
Relevant Websites http://www.nutrition.org/ American Society for Nutrition.
http://www.celiac.org Celiac Disease Foundation. http://www.cdhnf.org Children’s Digestive Health and Nutrition Foundation. http://www.ccfa.org Crohn’s and Colitis Foundation of America. http://www.cff.org Cystic Fibrosis Foundation.
Nutritional Management PM Tsai, University of California, San Francisco, CA, USA C Duggan, Harvard Medical School, Boston, MA, USA r 2013 Elsevier Ltd. All rights reserved.
Glossary Anthropometrics Body measurements used to determine body fat composition. Bioelectrical impedance A method that uses a small electrical current to measure body composition. DEXA scan A dual energy X-ray absorptiometry scan that uses X-ray beams to measure bone density and/or body composition.
Introduction The human gastrointestinal tract has an impressive capacitance for water, electrolyte, and nutrient absorption. In some disease states, however, this excess capacity is outpaced by either intestinal secretion or inadequate absorption. Malabsorption is defined as the inability of the gastrointestinal tract to adequately absorb nutrients. Although strictly speaking, malabsorption is distinct and contrasted with maldigestion (inadequate breakdown of nutrients in the intestinal lumen); the therapeutic implications of these two conditions are often similar. Multiple causes of malabsorption exist and reviews of these individual diagnoses can be found in separate sections of this text (e.g., inflammatory bowel disease, cystic fibrosis, short bowel syndrome, etc.). The pathophysiology, symptoms, and nutritional therapies for common malabsorption syndromes have been reviewed.
Pathophysiology and Symptoms Malabsorption can occur when any of the several steps in nutrient digestion, absorption, and/or assimilation are interrupted; see Table 1 for a list of congenital defects in nutrient assimilation. Carbohydrate malabsorption can occur, for instance, when intestinal disaccharidases are reduced in concentration at the enterocyte. The brush border membrane produces four disaccharidases that are important in carbohydrate digestion. These enzymes are sucrase-isomaltase, maltase-glucoamylase, trehalase, and lactase-phlorizin hydrolase. Worldwide, lactase deficiency is the most common type of acquired disaccharidase deficiency. With lactase deficiency, malabsorbed carbohydrate remains in the intestinal lumen and exerts an osmotic pull on fluids and electrolytes, leading
136
Endoscopy A procedure that uses an instrument to look inside the body for diagnostic or therapeutic purposes. Protein hydrolysate A type of formula in which proteins are broken down into smaller peptides by hydrolysis.
to abdominal cramping and loose stools. Malabsorbed carbohydrate can be metabolized by gastrointestinal tract bacteria, and the fermented gas produced is associated with flatulence and bloating. Bacterial overgrowth of the small intestine, as seen with short bowel syndrome, can also be associated with carbohydrate malabsorption. Steatorrhea, excessive fat in the stools, results from fat malabsorption or maldigestion and can have several causes, most notably pancreatic insufficiency due to cystic fibrosis, chronic pancreatitis, Shwachman-Diamond syndrome, and Johanson-Blizzard syndrome. Failure of pancreatic secretion of lipase, amylase, and other digestive enzymes leads to persistence of dietary fat in the intestinal lumen, causing bloating, abdominal pain, and bulky, foul-smelling, oily stools. The stools often float due to a high gas content and test positive for fat. Patients also complain of blunted appetite and nausea. Other causes of fat malabsorption include hepatobiliary disease with inadequate bile salt circulation, severe mucosal disease, and short bowel syndrome. The most common cause of protein malabsorption is socalled protein-losing enteropathy. Etiologies include diffuse mucosal disease such as celiac disease or Crohn’s disease, elevated right heart pressure with resultant dilatation of lymphatics and leakage of lymph into the lumen, and invasive enteropathies as seen with Shigella or Salmonella infections. Because protein is a relatively minor component of dietary energy compared with carbohydrate and fat, symptoms of protein malabsorption can sometimes be minimal. However, infectious colitis or exacerbations of inflammatory bowel disease often present with frequent loose stools, which may be bloody. Rarely, congenital etiologies of protein malabsorption include enterokinase and trypsinogen deficiencies (Table 1). Finally, the malabsorption of various micronutrients can occur in conjunction with or separate from the macronutrient
Encyclopedia of Human Nutrition, Volume 3
http://dx.doi.org/10.1016/B978-0-12-375083-9.00178-1
Malabsorption Syndromes: Nutritional Management
137
Table 1 Congenital defects in nutrient assimilation. Included are congenital defects that are associated with gastrointestinal symptoms and/or nutritional deficiencies. Congenital defects not included here include multiple defects in amino acid absorption Disorder
Gene/protein affected
Symptoms
Carbohydrate digestion Congenital lactase deficiency Hypolactasia Congenital sucrase-isomaltase deficiency
Lactase Lactase Sucrase-isomaltase
Lactose-induced diarrhea Lactose-induced diarrhea Sucrose-induced diarrhea
Carbohydrate absorption Glucose–galactose malabsorption Fructose malabsorption Fanconi-Bickel syndrome
Sodium-glucose-co-transport (SGLT1); SLC5A1 Facilitative fructose transport (GLUT5); SLC2A5 Facilitative glucose transport (GLUT2); SLC2A2
Glucose-induced diarrhea Fructose-induced diarrhea Diarrhea and nephropathy
Protein digestion Enterokinase deficiency Trypsinogen deficiency
Serine protease 7 Trypsinogen
Diarrhea and edema Diarrhea and edema
Fat digestion Pancreatic lipase deficiency
Pancreatic lipase
Steatorrhea
Microsomal triglyceride transfer protein Apolipoprotein B Sar1-ADP-ribosylation factor family GTPases Sodium-bile acid transporter; SLC10A2 ATP-binding cassette transporter 1 ATP-binding cassette, subfamily G, member 8; ABCG8
Steatorrhea Steatorrhea Steatorrhea Steatorrhea, bile acid diarrhea Hepatosplenomegaly Atherosclerosis
Ion and metal absorption Congenital sodium diarrhea Congenital chloride diarrhea Cystic fibrosis Acrodermatitis enteropathica Menkes disease Primary hypomagnesemia Hemachromatosis
Defective Na þ /H þ exchange Defective Cl /HCO3 exchange CFTR Zinc and iron-regulated transport proteins; SLC39A4 Copper transporter Paracellin 1; claudin 16 Hepcidin, others
Secretory diarrhea Secretory diarrhea Pancreatic insufficiency, meconium ileus Diarrhea and dermatitis Developmental delay Seizures, deafness and polyuria Cirrhosis, cardiomyopathy, diabetes
Vitamin absorption Folate malabsorption
? Intrinsic factor Cubilin, amnionless Transcobalamin II Thiamine transport protein; SLC19A2 Retinol-binding protein 4
Macrocytic anemia, diarrhea, developmental delay Macrocytic anemia, developmental delay Anemia, proteinuria Anemia, diarrhea, developmental delay Anemia, diabetes, cranial nerve defects Ophthalmologic problems
Alpha-tocopherol transport protein
Vitamin E malabsorption
Fat assimilation Abetalipoproteinemia Hypobetalipoproteinemia Chylomicron retention disease Primary bile acid malabsorption Tangier disease Sitosterolemia
Congenital pernicious anemia Imerslund-Graesbeck syndrome Congenital deficit of transcobalamin II Thiamine-responsive megaloblastic anemia Familial retinol binding protein (RBP) deficiency Selective vitamin E deficiency
Source: Adapted from Martin M and Wright EM (2008) Congenital intestinal transport defects. In: Kleinman RE, Goulet O, Mieli-Vergani G, Sanderson IR, Sherman P, and Shneider B (eds.) Walker’s Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 5th edn., p. 290. Hamilton, Ontario: BC Decker.
malabsorption syndromes noted above. For instance, steatorrhea can be accompanied by excessive fecal losses of the fat soluble vitamins A, D, E, and K, as well as calcium and other minerals. Alternatively, atrophic gastritis or surgical resection of the terminal ileum can lead to Vitamin B12 malabsorption in the absence of any symptoms of diarrhea. Proximal bowel resection can result in iron, zinc and calcium malabsorption. A rare cause of micronutrient inadequacy is abetalipoproteinemia in which fat soluble nutrients are normally digested and absorbed by the intestine but are not delivered to the circulation due to defective transepithelial transport. Other rare causes of micronutrient malabsorption are noted in Table 1.
General Nutritional Management of Malabsorption As with all nutritional disorders, a thorough nutritional assessment is needed to plan rational therapy of malabsorption. Important historical points to review include duration of symptoms, underlying etiology of malabsorption, ability to meet nutritional needs by mouth, presence of food allergies, and concurrent medical and surgical problems. The patient’s nutritional status (weight, height, body mass index, and their respective percentiles) should be determined. Tests of body composition such as arm anthropometrics, bioelectrical impedance, or DEXA scan should be considered. If the
138
Malabsorption Syndromes: Nutritional Management
underlying cause of malabsorption is not known, diagnostic gastrointestinal endoscopy, laboratory studies, and/or imaging studies are indicated.
Specific Nutritional Management of Malabsorption Fluids and Electrolytes Diarrhea is usually the most distressing problem for patients with malabsorption and may cause dehydration. Care should be taken to correct fluid losses with appropriately designed oral rehydration solutions. Even in the setting of massive secretory diarrhea such as seen with cholera infections, oral rehydration solutions are effective at treating dehydration. Recent data have supported the safety and efficacy of oral rehydration solutions of reduced osmolarity in children with dehydration from acute diarrhea. An oral rehydration solution with the following composition: glucose 75 mmol l1, sodium 75 mmol l1, potassium 20 mmol l1, base 30 mEq l1, and osmolality 245 mOsm l1 is well-suited for the rehydration and maintenance therapy during dehydration due to diarrhea. In some cases of severe diarrhea, parenteral hydration is the mainstay of therapy. Examples include glucose–galactose malabsorption, congenital chloride diarrhea, microvillous inclusion disease, and tufting enteropathy. These cases, as well as other severe causes of more common malabsorptive syndromes, also frequently require the use of parenteral nutrition therapy.
Carbohydrate Malabsorption Lactose Intolerance Lactose intolerance is defined by the occurrence of symptoms after ingestion of lactose, the main carbohydrate in milk. These symptoms may include abdominal pain, bloating, diarrhea, or flatulence. Lactose intolerance is usually secondary to lactose malabsorption caused by a relative deficiency of the disaccharidase lactase, which reduces the ability to digest lactose. Primary lactase deficiency is a condition in which lactase activity falls after weaning around 2 years of age. Secondary lactose intolerance may be temporary and is usually due to mucosal injury associated with a condition or disease such as infectious diarrhea, Crohn’s disease, or short bowel syndrome. In addition to the presence or absence of the lactase enzyme, other factors determine whether a person will have symptoms of lactose malabsorption, including the amount of lactose in the diet, the mixture of lactose with other foods, gastric emptying rate, colonic scavenge of malabsorbed carbohydrate, ethnic origin and age. Although persons of Northern European ancestry commonly maintain the ability to digest lactose into adulthood, primary lactose intolerance is prevalent in African–American, Hispanic, Native American, and Asian populations. Nutritional management of lactose intolerance consists largely of the removal of lactose from the diet. Lactose is a common ingredient in many foods, including breads, crackers, soups, cereals, cookies, and baked goods. Eliminating or reducing lactose-containing ingredients from one’s diet is
Table 2
Commercial calcium supplements
Product
Manufacturer
Mg Calcium/ tablet
IU vitamin D
Citracal Regular OsCal 500 þ D Tums Calcium Milk Free Cal-citrate þ D Caltrate 600 þ D Viactiva
Bayer GlaxoSmithKline GlaxoSmithKline Nature’s Plus
500 500 500 250
400 200 0 50
Freeda Pfizer McNeil Nutritionals
250 600 500
100 400 500
a
This product contains less than 0.5 mg lactose. Source: Adapted from DiSanto C and Duggan C (2005) Gastrointestinal diseases. In: Hendricks KM and Duggan C (eds.) Manual of Pediatric Nutrition, 4th edn., p. 212. Hamilton, Ontario: BC Decker.
usually adequate to relieve symptoms. Individuals with primary lactose intolerance may require a permanent dietary change. Individuals with secondary lactose intolerance should eliminate all lactose from their diets for a short period of time ranging from 2 to 6 weeks. If symptoms resolve, lactose may be reintroduced slowly as tolerated by the individual. The amount of lactose that an individual can tolerate is highly variable. Many children can tolerate small amounts of lactose, particularly yogurt or hard cheese, without discomfort. Many adults who consider themselves lactose intolerant can actually tolerate moderate amounts of milk. Lactose intolerant individuals may also tolerate small amounts of lactose consumed over the course of the day better than a large dose all at once. For individuals who choose to restrict lactose in their diets, a variety of lactose-free and low-lactose food choices are available. Lactose-reduced products, containing 70–100% less lactose than standard foods, are available commercially. Individuals may also choose to consume dairy products with concomitant administration of lactase enzyme tablets or drops. Frequent consumption of milk and other dairy foods has been associated with better bone health in some studies, and a strict lactose-free diet may not contain adequate amounts of calcium and vitamin D. Table 2 provides a list of some commercially available lactose-free and lactose-reduced calcium supplements.
Sucrose Congenital sucrase-isomaltase deficiency (SID) is the most common congenital disaccharidase deficiency. Patients with this disorder lack functional sucrase, although isomaltase deficiency may be normal or absent. Symptoms of SID can include diarrhea, abdominal pain, and poor weight gain. Dietary avoidance of sucrose or table sugar helps relieve symptoms, and can sometimes help with the diagnosis. Sucraids, a sacrosidase produced from Saccharomyces cerevisiae, is an enzyme that can be given with meals and allows increased tolerance to sucrose.
Fat Malabsorption: Fat and Fat-Soluble Nutrients Patients with pancreatic insufficiency are unable to produce and secrete enough enzymes to aid with the breakdown of fats
Malabsorption Syndromes: Nutritional Management
in the intestinal lumen. In studies of normal adults and those with pancreatic insufficiency, pancreatic enzyme secretion needs to be lower than 15% of normal levels before significant steatorrhea is seen (Figure 1). Once clinically significant steatorrhea is determined, recovery of pancreatic function is therefore unlikely. Historically, patients with pancreatic insufficiency due to cystic fibrosis (CF) were told to minimize symptoms of steatorrhea by limiting dietary fat. However, epidemiologic studies confirmed that this advice lead to negative energy balance, undernutrition, and higher mortality rates, compared to communities in which CF patients were treated with high-energy and high-fat diets. The introduction of effective pancreatic replacement therapy has been heralded as one of the most significant breakthroughs in the nutritional management of CF, responsible partly for the substantial increase in lifespan enjoyed by more recent generations of CF patients. In fact, the finding of a lower incidence of growth failure in CF patients diagnosed and treated with aggressive nutritional therapy early in infancy has been used as justification for neonatal screening of this condition. Judicious use of pancreatic replacement enzymes is the hallmark of nutritional therapy of CF and other disorders of pancreatic insufficiency. Multiple commercial preparations of porcine pancreatic enzymes are available, most of which contain lipase, amylase, and protease enzymes. A nonporcine pancreatic enzyme is currently under development. The dose is usually titrated to the amount of steatorrhea. If meals take more than 30 min, the dose may be divided with half given before the meal and half given mid-way through the meal. Patients who cannot swallow pills may open the capsules and sprinkle the enzymes into acidic foods. Another critical aspect of the nutritional management of fat malabsorption is routine supplementation with the
Fecal fat (gm/24 hr)
100
75
Health EAA ID Pancreatic disease EAA ID CCK-PZ IV
50
25 Upper limit of normal 0
12
25
(<15% of normal)
50
75
100
139
fat-soluble vitamins A, D, E, and K. Multiple studies have confirmed that patients with CF, Crohn’s disease, and other malabsorptive disorders are prone to micronutrient deficiencies, and some literature suggests that dietary needs for these and other antioxidant nutrients may be increased in settings of infectious and catabolic stress often suffered by these patients. The contribution of fat malabsorption contributing to other important mineral malabsorption, as in the case of calcium or zinc, should also be recognized. Routine supplementation of fat-soluble vitamins is indicated in patients with fat malabsorption. In addition, serial measurement of fat-soluble vitamin biochemical status is recommended. Because blood nutrient concentrations of these and other nutrients can vary with the concentration of transport proteins, correction for these can aid the interpretation of these lab findings. For instance, vitamin A toxicity should be suspected if the molar ratio of vitamin A: Retinolbinding protein exceeds 1. Vitamin E concentrations, for example, should be corrected for circulating lipids. Some patients with pancreatic malabsorption may benefit from a diet enriched in medium chain triglycerides (MCTs). MCTs are absorbed directly into the portal circulation and therefore bypass the steps of intraluminal digestion, reesterification, and enterocyte uptake. Therefore, these fats may be a dietary source of fats more easily absorbed in settings of fat malabsorption due to either pancreatic insufficiency or mucosal disease. However, MCT oils are less energy dense than long-chain fats, are more expensive, and do not contain the essential fatty acids alpha-linoleic and linolenic acid.
Protein Malabsorption Protein-losing enteropathy (PLE) can also be treated with a variety of nutritional interventions. PLE due to dilated lymphatics as with right heart failure results in leakage of lymphocytes, proteins, and fats into the intestinal lumen. As with fat malabsorption, MCT-supplemented foods and formulas are therefore indicated to allow improved fat absorption in PLE. Fat-soluble vitamin supplementation is indicated. In congenital protein malabsorption syndromes, peptide- or amino acid-based formulas are often helpful. Mucosal disorders including inflammatory bowel disease, allergic diseases, and celiac disease are other examples of disorders causing protein malabsorption. Once intestinal inflammation is reduced with appropriate medical or nutritional therapy, absorption of protein is usually improved. In Shigella infections, some studies have suggested improved nutritional outcomes with a high-protein diet during recovery from the acute symptoms of diarrhea.
125
Lipase output (kU hr −1)
Figure 1 Pancreatic enzyme secretion and steatorrhea. Significant steatorrhea ensues when pancreatic function is less than 15% of normal. Reproduced with permission from DiMagno EP, Go VLW, and Sumerskill WHJ (1973) Relations between pancreatic enzyme output and malabsorption in severe pancreatic insufficiency. New England Journal of Medicine 288: 814. Copyright r 1973 Massachusetts Medical Society. All rights reserved.
Route of Nutrition in Malabsorption Several factors need to be considered when recommending whether oral, enteral, or parenteral nutrition should be used in providing nutrition to the patient with malabsorption. These factors include etiology of malabsorption, severity of gastrointestinal disease, and underlying nutritional and medical conditions. Oral nutrition using modified diets as noted above is, of course, the most customary and desirable by
140
Malabsorption Syndromes: Nutritional Management
physician and patient alike. In cases of mild lactose malabsorption, for instance, modification of a regular, healthy diet to avoid foods high in lactose should be sufficient. In cases where widespread gastrointestinal disease is leading to severe malabsorption, enteral or ‘tube’ feeding is helpful for two main reasons: (1) use of proprietary formulas specially designed for malabsorption are often indicated, and these formulas may be unpalatable, and (2) enteral feedings, especially with slow continuous ‘drip’ feedings make efficient use of nutrient transport kinetics, thereby maximizing residual gastrointestinal absorptive function. In severe cases of malabsorption in which tube feedings are unable to achieve adequate nutritional intake, parenteral nutrition may be indicated. Emerging data suggest that serum citrulline, an amino acid synthesized principally by the enterocyte, is a reliable biomarker of mucosal mass and may help distinguish among patients who require parenteral versus enteral nutrition.
Selection of Enteral Formulas for Malabsorption A number of commercially available formulas are designed for patients with malabsorption, and these differ with regard to energy density, macronutrient composition, and indicated age. Because infant formulas are often handled in a separate regulatory fashion by governments, infant formulas are usually considered separately from formulas designed for older children and adults. In addition, formulas are also conventionally categorized by the extent of the hydrolysis of their protein source. Categories include intact protein formulas, protein hydrolysate formulas, and amino acid-based formulas. Protein hydrolysate formulas are also sometimes referred to as ‘semielemental’ formulas, and amino-acid formulas are sometimes called ‘elemental’ formulas. However, these terms suffer from vagueness and inaccuracies because not all of their macronutrients are semi or completely elemental. Marketing strategies often compound the confusion with misleading formula names. These terms should be discouraged, and the terms that refer to the composition and/or biochemical processing should be used instead. Patients who have carbohydrate malabsorption from lactose intolerance should use lactose-free formula. Fat malabsorption may call for MCT enriched formula. In cases of protein malabsorption or severe enteropathy, a formula that is a protein hydrolysate or amino acid based would be most appropriate. Because many malabsorption syndromes overlap in terms of the macronutrient affected, as in cases of severe mucosal disease, some formulas are designed for fat, protein, and carbohydrate malabsorption. For example, all formulas designed for use in adults are lactose free, and several formulas contain both hydrolyzed proteins and MCT oils.
Clinical Management of Malabsorption Two of the most clinically challenging scenarios for the management of malabsorption are inflammatory bowel disease (especially Crohn’s disease) and short bowel syndrome. Both are discussed in separate articles of the text, but are considered briefly below.
Inflammatory Bowel Disease Patients with Crohn’s disease have widespread and intermittent gastrointestinal inflammation. Some patients with inflammatory bowel disease may require complete bowel rest for several days or even a few weeks to allow time for mucosal healing. To provide nutrition during this period of time, parenteral nutrition may be needed. Numerous studies have shown that patients with Crohn’s disease may safely and effectively achieve clinical remission with primary nutritional therapy. Early literature in the field highlighted the use of protein hydrolysate formulas, which, due to unpalatability, often required administration via a nasogastric or gastrostomy tube. More recent data have confirmed that intact protein formulas, termed ‘polymeric’ formulas when describing formulas designed for adults, may work as well as protein hydrolysates, and these formulas can be feasibly given by mouth. As patients are recovering from an exacerbation and begin advancing their diet, patients should temporarily minimize the amount of fiber ingested to decrease trauma to healing mucosa. Patients whose disease affects the small intestine often benefit from temporary avoidance of lactose products as the mucosa heals and brush border membrane enzyme production is restored. Micronutrients are also needed in the nutritional management of inflammatory bowel disease. Iron supplementation is recommended for anemia due to acute or chronic blood loss. Treatment of inflammatory bowel disease frequently requires the use of steroids, which affects bone density. Calcium and vitamin D supplementation is commonly needed to minimize the osteopenic effects of steroid therapy and/or the effects of malabsorption and chronic inflammation.
Short Bowel Syndrome Patients who have suffered acquired or congenital loss of small intestinal surface area that makes them dependent on specialized enteral or parenteral support are said to have short bowel syndrome (SBS). Patients with SBS often malabsorb carbohydrates, proteins, fat, as well as numerous micronutrients, depending on the extent and location of bowel resection, as well as the presence of mucosal disease in the nonresected bowel. Special attention should be given to exactly what part of the intestine remains as well as the length of the remaining intestine. Some patients may have the terminal ileum removed and are unable to absorb vitamin B12 and bile acids. Removal of the ileocecal valve increases the risk of bacterial overgrowth. Reduced length also means reduced surface area for the absorption of nutrients and decreased intestinal transit time. In the immediate postoperative period, parenteral nutrition and gut rest should be used because significant stool output is the norm. Output should be quantified, and electrolytes must be carefully monitored in order to determine appropriate replacement fluids to make up for excess urine, stool, and ostomy losses. Replacement fluids should generally be given separately from standard parenteral nutrition so that
Malabsorption Syndromes: Nutritional Management
Table 3
141
Feeding advancement in short bowel syndrome
1. Stool output Ifo10 g kg 1 d 1 or o10 stools d 1 If 10–20 g kg 1 d 1 or 10–12 stools d 1 If420 g kg 1 d 1 or412 stools d 1 or 2. Ileostomy output Ifo2 g kg 1 h 1 If 2–3 g kg 1 h 1 If43 g kg 1 h 1 3. Stool reducing substances Ifo1% If¼1% If41% 4. Signs of dehydration If absent If present 5. Gastric aspirates o four times previous hour’s infusion 4 four times previous hour’s infusion
Advance rate by 10–20 ml kg d 1 no change Reduce rate or hold feedsa Advance rate by 10–20 ml kg 1 d 1 no change Reduce rate or hold feedsa Advance feeds per stool or ostomy output no change Reduce rate or hold feedsa Advance feeds per stool or ostomy output Reduce rate or hold feedsa Advance feeds Reduce rate or hold feedsa
a
Feeds should generally be held for 8 h, then restarted at 3/4 the previous rate. Source: Adapted from Utter SL and Duggan C (2005) Short bowel syndrome. In: Hendricks KM and Duggan C (eds.) Manual of Pediatric Nutrition, 4th edn., pp. 728–729. Hamilton, Ontario: BC Decker.
they can be adjusted as needed to rapid shifts in fluid and electrolyte status. As patients recover from surgery, every attempt should be made to feed them enterally as soon as is feasible. Enteral feeds facilitate growth and adaptation of the remaining bowel to allow partial compensation for the missing portion, and several studies have correlated early feeding with better longterm outcome. Attaining independence from parenteral nutrition may take weeks to months to years. Table 3 outlines an approach to determine feeding advancement in SBS. Although some patients are able to grow well or maintain their body weight with only enteral feeds, many are dependent on parenteral nutrition. Some patients with SBS also have oral feeding aversion due to prematurity, prolonged mechanical ventilation, and/or prolonged orogastric or nasogastric feeding. Gastrostomy tubes are particularly helpful in this regard. In infants, breast milk should be used if available. The breast milk may need to be fortified to increase calories, protein, or fat. For older patients or infants who are not receiving breast milk, protein hydrolysates or amino acid-based formulas may be better tolerated because the residual bowel more easily absorbs these nutrients. Lactose-free and MCTcontaining formulas are often used, as well. Formulas may need to be supplemented with oral rehydration solutions if electrolyte abnormalities persist, particularly with sodium losses through persistent high stool or ostomy output. Because many patients with SBS are dependent on parenteral nutrition for prolonged periods of time, selenium, carnitine, copper, and zinc blood concentrations should be checked periodically and supplemented if needed. Parenteral nutrition should be cycled off for a few hours each day to help simulate more natural cyclic fluctuations of gastrointestinal hormones. These patients also often have poor absorption of calcium and need calcium supplements to prevent osteopenia, which increases the risk of fractures. Iron may also be needed in patients with anemia from decreased absorption secondary to resection of the duodenum or jejunum. Ultimately,
weaning from parenteral and enteral nutrition remain the goals of treatment, though lifelong dietary therapy is often needed.
Summary Congenital or acquired diseases of the gastrointestinal tract can lead to life-threatening malabsorption of numerous macronutrients and micronutrients. Determining the type and etiology of malabsorption is essential to provide appropriate nutritional and medical therapy. Multiple formulas, supplements, and dietary regimens exist to target specific defects in the digestion, absorption, and assimilation of nutrients. In addition, many new nutrients are undergoing investigation that may become a standard part of care in the future, including probiotics, prebiotics, and various amino acids.
See also: Celiac Disease. Cystic Fibrosis. Lactose Intolerance
Further Reading Ce´zard JP (2008) Normal physiology of intestinal digestion and absorption. In: Kleinman RE, Goulet O, Mieli-Vergani G, Sanderson IR, Sherman P, and Shneider B (eds.) Walker’s Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, 5th edn., pp. 245–252. Hamilton, Ontario: BC Decker. Crenn P, De Truchis P, and Neveux N (2009) Plasma citrulline is a biomarker of enterocyte mass and an indicator of parenteral nutrition in HIV-infected patients. American Journal of Clinical Nutrition 90(3): 587–594. Holt PR (2007) Intestinal malabsorption in the elderly. Digestive Diseases 25: 144–150. Iannitti T and Palmieri B (2010) Therapeutical use of probiotic formulations in clinical practice. Journal of Clinical Nutrition In press.http://dx.doi.org/10.1016/ j.clnu.2010.05.004. Olieman JF, Penning C, Ijsselstijn H, et al. (2010) Enteral nutrition in children with short-bowel syndrome: Current evidence and recommendations for the clinician. Journal of the American Dietetic Association 110: 420–426.
142
Malabsorption Syndromes: Nutritional Management
Rubio-Tapia A and Murray JA (2010) Celiac disease. Current Opinion in Gastroenterology 26: 116–122. Shikhare G and Kugathasan S (2010) Inflammatory bowel disease in children: Current trends. Journal of Gastroenterology 45: 673–682. Stallings VA, Stark LJ, Robinson KA, et al. (2008) Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: Results of a systematic review. Journal of the American Dietetic Association 108: 832–839. Treem WR, McAdams L, Stanford L, et al. (1999) Sacrosidase therapy for congenital sucrase-isomaltase deficiency. Journal of Pediatric Gastroenterology and Nutrition 28: 137–142.
Relevant Websites http://www.nutrition.org/ American Society for Nutrition.
http://www.celiac.org Celiac Disease Foundation. http://www.cdhnf.org Children’s Digestive Health and Nutrition Foundation. http://www.ccfa.org Crohn’s and Colitis Foundation of America. http://www.cff.org Cystic Fibrosis Foundation.