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1 NUTRITIONAL CONSEQUENCES OF ACUTE DIARRHEA INTRODUCTION Nearly all children suffer from diarrhea. Preschool children in some developing countries have diarrhea 10-20% of the time, or about 35-70 days a year.5 Depending on etiology, as many as 10% of children with diarrhea become severely dehydrated and 0.5% of all those with diarrhea may die of it.4& Oral dehydration therapy (ORT) saves lives by replacing lost body fluids and electrolytes. If universally used, ORT could signi- ficantly reduce diarrhea-related mortality and morbidity. Besides causing a loss of water and electrolytes, acute diarrhea has important adverse effects on the nutritional status of a child. Among the common infec- tious diseases, diarrhea! diseases are the most common contributors to malnutrition. In industrialized countries, nutritional reserves of children are generally sufficient to offset the detri- mental effects of diarrhea. The greater availability of high-quality foods and the lower incidence of diarrhea in individual children also reduce its adverse nutri- tional consequences by permitting rapid catch-up growth during convalescence. In some developing countries, however, 30% or more of the children may be moderately to severely malnourished. In a malnourished child, even a brief episode of diarrhea can seriously affect nutri- tional status and require prompt attention to prevent further nutritional deterioration and its consequences. Furthermore, the high frequency of diarrhea allows less time for recovery and catch-up growth between episodes.

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Diarrhea contributes to malnutrition through reduc- tion in food intake, decrease in absorption of nutrients, and increase in catabolism of nutrient reserves. Physio- logic causes of a decrease in food intake include anorexia, nausea, and vomiting, all of which may be associated with electrolyte loss, imbalance, and dehy- dration, although the exact mechanisms are not well defined. Maldigestion and malabsorption can occur in children in whom intestinal digestive enzyme activity is decreased and transit through the intestine is more rapid. Malabsorption is excerbated by the preferential destruction of mature cells often caused by the infec- tion. Some invasive bacteria (e.g., shigellae), viruses (e.g., measles), and protozoa (e.g., amebae) can direct- ly damage the intestinal lining and lead to protein loss. Bacterial overgrowth in the upper portions of the intestine can accentuate malabsorption, and competition with intestinal helminths and bacteria for available nutrients can reduce the availability of food to the child. Fever, generally associated with invasive intes- tinal organisms, results in increased metabolic rates, which lead to increased energy requirements and losses of muscle and visceral protein. In addition, food is often withheld during the acute illness. These nutritional consequences of diarrhea, described in some detail in this chapter, often set the stage for more severe illness, which can lead to increasingly severe nutrient deficiencies. The potential for the accelerated deterioration of nutritional status demands that lost fluids and nutrients be rapidly replaced. DECREASE IN DIETARY INTAKE Hospital-based investigations of dietary intake by children with diarrhea have consistently shown a reduc- tion in food intake, and hence caloric intake, during their illness. The findings vary considerably with the site of the study, the comparison group used, and the children's major sources of dietary energy. Three clinical studies from Bangladesh noted a 30-50% decrease in caloric intake during the early days of illness, compared with an illness-free control group or with the same patients after recovery from diarrhea.l8~31~45 The comparison groups were offered a relatively energy- dense hospital diet frequently throughout the day and

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thus consumed substantially more energy than illness- free children from the same country who consumed their usual diet. The apparent decrease in energy consumption during illness would presumably be smaller if estimated on the basis of the usual dietary intake at home. No significant decrease in breast-milk consumption was detected during illness in the two studies in which it was measured.l8~45 Three community-based studies of dietary intake during illness have produced conflicting results. Two reports from Central America identified a reduction in energy consumption by young children who were completely weaned from the breast.27~28 In these field studies, the decrease in energy consumption averaged only 15-20%, possibly because the energy consumed was compared with the children's usual intake, not with a hospital diet. In contrast, a recent study of Bangladeshi infants, who were still receiving most of their dietary energy from breast milk, did not find significant decreases in energy intake during diarrhea.6 Many explanations for the observed reductions in energy intake are possible, including food withholding (as dictated by parental beliefs or recommendations by health-care personnel), substitution of nutrient-poor Dehydration solutions for other dietary components, reduction in the nutrient density of the diet, vomiting, and anorexia. No studies have attempted to distinguish among these factors, and data are insufficient to deter- mine how diarrhea affects dietary intake or to assess the impact on appetite of specific metabolic disturb- ances, such as acidosis and electrolyte imbalances. Despite all efforts to encourage continued feeding during diarrhea, net nutrient losses occur, in part because of anorexia (unavoidable in some cases), malabsorption, and increased catabolism. 21,30,31 In growing children, these losses are manifested by a slowing of growth or by persistent weight loss even after full Dehydration. Consumption greater than normal is required during convalescence to compensate for nutrient losses and to permit catch-up growth. Indeed, young undernourished children fed energy-rich and protein-rich foods increase their intake substantially and might gain weight at up to 7 times the expected rate until they catch up to their optimal nutritional

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status.50~51 However, the traditional weaning diets in many societies are composed primarily of staple foods that are diluted to a semisolid consistency. The bulkiness of this diet limits the amount of food that can be consumed and therefore limits the rate of catch-up growth. High-quality, well-balanced, energy-dense foods must be added to such diets during illness and recovery if the catch-up growth rate is to be optimal and preillness nutritional status is to be restored. DECREASE IN INTESTINAL ABSORPTION Digestion and absorption are complicated and involve several organ systems acting in concert. Protein requires digestion by proteolytic enzymes, primarily pancreatic, before it is absorbed as small peptides and amino acids. Triglycerides, the major form of dietary lipid, must be digested by lipases to their component fatty acids and monoglycerides and then be incorporated with bile acids into water-miscible, mixed micelles for efficient absorption. Starches are broken down to oligo- saccharides (primarily maltose and dextrins) by salivary and pancreatic amylase and in part by brush-border enzymes. These oligosaccharides and dietary sugars are ultimately hydrolyzed by brush-border disaccharidases before active or facilitated transport of the component monosaccharides across the cellular membrane can occur. Some vitamins and minerals have specific intestinal transport pathways. The intestinal villus cells, which are partly responsible for digestion and absorption of dietary components, migrate upward from the crypts of the mucosa to the villus tips and are eventually sloughed into the intestinal lumen. The entire intestinal surface is renewed about every 3 days. Mucosal renewal probably requires stimulation by the diet and pancreatic secre- tions. During chronic starvation and after acute with- drawal of food, mucosal cell turnover and production of brush-border hydrolytic enzymes decrease. Withholding of food to control diarrhea might thus contribute to mucosal abnormalities and worsen malabsorption and diarrhea when feeding is reintroduced. — 4 —

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The efficiency of intestinal absorption is deter- mined not only by the physiologic maturity and state of health of the child, but also by the dietary sources of particular nutrients. In general, breast milk and other foods derived from animal sources are more readily - - The digestibility and bioavailability of nutrients from vegetable products, however, vary widely according to the specific food, the way it is processed, and the extent of cooking. Interactions among specific foods or nonnutritive components (such as phytates, tannins, and fiber) can also influence digestion and absorption of individual nutrients. These factors should be consider- ed in planning the dietary management of persons with diarrhea. digested than those obtained trom plant sources. Intestinal absorption is commonly impaired during and after acute intestinal infections in humans.8~41 Because the gastrointestinal system is not fully mature at birth, infants and young children might be particular- ly susceptible to the adverse effects of intestinal infections on digestive and absorptive capacity. Clini- cal studies of children with acute intestinal infections have documented malabsorption of macronutrients carbohydrates, fat, and protein. __ · Transient malabsorption of carbohydrates has been observed often, especially in episodes of viral origin.24~42 This malabsorption is presumably caused by secondary disaccharidase deficiencies, impairment in monosaccharide transport, alterations in intestinal motility, and loss of intestinal surface area. It remains unknown whether intestinal infections alter pancreatic function, either directly or by reducing the endocrine stimulation of pancreatic secretion by damaged intestinal mucosa. o Malabsorption of fat is common during and after diarrhea.25 An increase in fecal excretion of bile acids, possibly secondary to impairment of ileal trans- port or to bacterial overgrowth in the small intestine, can result in intestinal bile acid concentrations that are too low for micelle formation, which is necessary for fat absorption.l9

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· The efficiency of protein absorption during diar- rhea has not been studied extensively, but marked loss of endogenous protein in stool can occur, especially with dysentery.40 Despite the demonstration of increased fecal nutrient losses during intestinal infections, substan- tial nutrient absorption occurs. Studies with either common mixed diets or synthetic formulas have found that an average of 80-90% of ingested carbohydrate, 50-70Z of fat, and 50-7 5Z of nitrogen are absorbed, depending on the food sources of these nutrients, the amounts ingested, and the type and severity of diarrhea.7~30 Thus, although absorption of macronutrients can be 10-30% lower than that in illness-free children consuming the same diets, nutrient absorption during diarrhea is sizable. This points to a nutritional advantage of continued feeding. In the few comparative studies that have been completed, increasingly high dietary intakes were associated with absorption of increasingly high amounts of ingested nutrients.7~12~26 Nutrient-balance studies, which measure the amounts of specific nutrients ingested and excreted in feces, do not distinguish between the excretion of exogenous (dietary) and endogenous nutrients. Febrile illnesses and intestinal infections with agents that invade the mucosa and cause inflammation result in losses of endo- genous nutrients. Fever increases the basal metabolic rate and energy requirements.21 It also triggers increases in urinary concentrations of a variety of trace minerals and an increase in tissue catabolism, which leads to substantial losses of nitrogen stores from contractile muscle and the viscera. The cumulative balance of these nutrients can remain negative for many days or even weeks after the onset of illness. During dysentery, the additional loss of blood and blood pro- teins can be large. These illnesses often precipitate acute protein-energy malnutrition of the kwashiorkor type if dietary intake is not kept high enough to offset these stress-induced losses. As noted earlier, in the absence of food intake, the turnover and maturation of intestinal cells lessen; that decreases the surface area available for the end stages of digestion and absorption. Pancreatic function also decreases in acute or chronic malnutrition. Even for these reasons alone, the continued feeding of nutrients in acute diarrhea is necessary. — 6

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INCREASE NUTRIENT REQUIREMENTS Age-specific nutrient requirements and recommended intakes or allowances for normally growing children are published periodically by national and international authorities.14~15~35 Recommended allowances are targeted to the needs of approximately 98% of the members of specified normal populations. Recommended allowances of most nutrients are calculated by estimat- ing average requirements for the population and adding some quantity to account for individual variability. Recommended intakes of energy beyond early infancy are calculated by summing average estimates of the needs for maintenance, growth, and activity. When the nutrient needs of an undernourished child with acute diarrhea are estimated, the nutrient losses imposed by the illness and by catch-up growth must be added to the baseline allowances for healthy children. There is no need for an additional allowance for physical activity, because that is included in the estimation of recommended allowances. Nutrient needs in diarrhea are increased because intestinal absorption is impaired, metabolic rates are increased, and tissue must be repaired. The increased needs are difficult to estimate. Age- and disease- specific data on children are meager; impairment of intestinal absorption in diarrhea is highly variable and might depend in part on the etiology of the illness. In the absence of fever or sepsis, needs for metabolism are not likely to be much more than 10% above normal. Nutrient needs for tissue repair are probably included in the estimates for catch-up growth. The metabolic cost of catch-up growth is easier to estimate than that of diarrhea. Once fluid losses have been corrected, the weight-for-height deficit can be determined. Although there is no consensus on the extra nutrient requirements for tissue accretion during catch-up growth, estimates of 5-8 kcal and approximately 0.4 g of protein per gram of desired gain of lean body mass appear reasonable. The daily caloric requirement for growth is approximately 2% of the recommended energy intake for a 2-year-old child.49 If diet is not limiting, catch-up growth after diarrhea might be as much as 7 times as great as average daily

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growth.50~51 Thus, 14% (i.e., 7 x 2%) more energy intake might be needed to provide for maximal catch-up. The comparable figures for protein are 12% of the daily allowance for growth and 84% (7 x 12%) for catch-up growth. To allow for additional factors that could interfere with utilization of food, it has been suggested that diets during periods of catch-up growth provide an increment of 30% of energy and 100% of protein.50 The above considerations suggest that the provision of energy at least 25% above the estimated mean requirement for normal children is a conservative goal during early convalescence. Estimates of energy intake and weight gain required for recovery from various categories of weight loss according to selected recovery periods are presented in the Appendix. , , A target protein intake of twice the recommended allowance would be an appropriate coal to cover losses due to malabsorption, . . . ~ . · . . . . . ~ ~ ~ ~ . . increases In needs that result from catabolic losses, and inefficient use when energy is inadequate because of lowered intake or malabsorption. . It must be recognized that these figures are only gross estimates of the actual requirement of a given child during recovery from illness. These estimates of intake should not be used bv themselves as the target of therapy. _ ~ Rather, the growth response of a child should be used to monitor the adequacy of dietary intake. POTENTIAL COMPLICATIONS OF CONTINUED FEEDING Although continued feeding during diarrhea is advocated for its favorable nutritional consequences, the potential complications of intestinal malabsorption must be considered. Unabsorbed water-soluble substances exert an osmotic force that draws water and, to a lesser extent, electrolytes into the intestinal lumen. Colonic bacterial fermentation of unabsorbed carbohydrate that reaches the large intestine produces short-chain organic acids, increases the number of small molecules, and thus contributes to systemic acidosis and augments diarrhea.47 Dietary intake that exceeds intestinal absorptive capacity can result in a greater risk of dehydration, electrolyte imbalance, and systemic acidosis. — 8 —

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Early studies of food intake during diarrhea found increased fecal losses in children who ate more. However, these studies used milk-based diets.12 Human milk appears to be well tolerated.8 Recent studies with lactose-free diets have found no increase in severity of diarrhea among children who consumed these diets, compared with children who received only oral glucose-electrolyte solutions.7~44

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