- Email: [email protected]
Diarrhea
10
DIARRHEA Gigi Veereman-Wauters • Jan Taminiau
Parents often consult a pediatric gastroenterologist with questions about their child’s stool pattern. Personal and cultural beliefs influence their perception of what may be a problem. Precise questions about the aspect of the child’s defecation pattern and the visual appreciation of a stool sample are important on the first encounter. Normal stool consistency and frequency evolve during childhood. It is commonly accepted that the evacuation of liquid or semiformed stools from 7 times a day to once every 7 days is normal in breast-fed babies. Formula-fed babies have more formed or even harder stools. Colic and cramping are eagerly attributed to difficult defecation. The latest innovations in infant formula are the addition of pre- or probiotics that are intended to favor a bifido-predominant intestinal flora and therefore softer stools.1 Defecation frequency and stool volume decrease from birth to 3 years of age when an “adult” pattern is reached. Infants pass 5 to 10 g/kg/day and adults an average of 100 g/day.2,3 There is an individual variation in what can be considered a normal stool pattern. Healthy toddlers may open their bowels more than three times a day,4 and stool consistency may be loose with identifiable undigested particles.5,6 However, in normal circumstances, intestinal nutrient and water absorption should be sufficient for homeostasis and growth of the organism. If such is not the case, fecal losses cause deficits and disease. In this chapter we discuss the clinical approach to pediatric patients with diarrhea and the differential diagnosis for different age groups. Specific etiologic conditions are discussed in other chapters.
PHYSIOLOGY OF INTESTINAL CONTENT HANDLING In adults, 8 to 10 L of fluid containing 800 mmol sodium, 700 mmol chloride, and 100 mmol potassium enters the proximal small intestine daily.7 Two liters comes from the daily diet, and the remainder from secretions of the salivary glands, stomach, biliary and pancreatic ducts, and proximal small intestine. The small intestine absorbs all but 1.5 L of this amount of fluid containing 200 mmol sodium/L; the colon absorbs all but 100 mL containing approximately 3 mmol sodium of the remaining fluid. Regardless whether a subject ingests a hypotonic meal, such as a steak with an osmolality of 230 mOsm/kg water, or a hypertonic meal, such as milk with a doughnut with an osmolality of 630 mOsm/kg water, the very permeable proximal small intestine allows movement of water and electrolytes into the lumen, rendering the meal isotonic with plasma as it reaches the proximal jejunum. The aforementioned secretions augment the volume of the 300-mL milk-doughnut meal to 1200 mL and the steak -meal from 600 to 2000 mL in the duodenum, and further increases the volume of the milk-doughnut meal to 2000 mL when starches and lactose are digested. In the jejunum, fluids and electrolytes are in equilibrium with plasma, allowing optimal absorption.8,9 106
Water absorption is only possible together with solutes. In the absence of food, all water is absorbed through the neutral NaCl carrier, located mainly in the ileum. This is the so-called sodium-hydrogen exchanger, as the negatively charged anions chloride and bicarbonate are exchanged. With the NaCl carrier a single molecule of sodium co-transports 50 molecules of water. After a meal, the glucose-galactose-sodium carrier (SGLT1), located mainly in the jejunum, transports most sodium and water. One molecule of sodium then co-transports 250 molecules of water.10 All macronutrient transport through the small intestinal epithelium is driven by Na+ transport: amino acids, dipeptides, and fatty acids. The maximal absorption for both the NaCl carrier and the SGLT1 is estimated at 5 to 7 L. After 2 m of small intestinal absorption by the nutrient sodium carriers, the chloride content diminishes, probably suggesting substantial postprandial use of the NaCl carrier.11 In the human colon water absorption is again dependent on Na+ absorption. Na+ is absorbed through an electrogenic process at the apical membrane and maintained by the basolateral Na,K-ATPase, which in each cycle extrudes three Na+ ions for two K+ ions. Another proportionally larger Na+ absorptive mechanism is the electrical neutral Na-Cl absorption in which Na+ is exchanged for H+ and Cl− for bicarbonate. This Na+ absorption is coupled with short-chain fatty acids (SCFAs). The proximal colon contains high luminal concentrations of organic nutrients (nonstarch polysaccharides from plant walls and proteins not absorbed by the small intestine) and high bacterial growth rates parallel high fermentation rates. Of the three SCFAs (acetate, propionate, and butyrate), butyrate is the most abundant and physiologically important. Butyrate serves as a major energy source for colonocytes and plays a crucial role in their growth and differentiation. The butyrate-bicarbonate exchange is the main driving force for Na-Cl absorption, each molecule co-transporting 50 molecules of water. Maximal absorption amounts to 3 to 5 L daily.12 The Na+ absorptive processes are restricted to small intestinal villous cells, whereas Cl− secretory processes are located in the small intestinal crypts. In the colon, Na+ absorption occurs in the crypts; consequently, additional hydraulic forces due to a small neck enlarge Na+ and water absorption enormously.13 This Na+ absorptive state is reversed to a Cl– secretory state under the influence of cAMP or calcium secretagogues. In the small intestine Cl– secretion induced by these secretagogues occurs mainly in the crypts.
DEFINITIONS OF DIARRHEA Feces contain up to 75% water. A relatively small increase in water losses will cause liquid stools. In infants, stool volume in excess of 10 g/kg/day is considered abnormal.3 Diarrhea is the frequent (more than three times a day) evacuation of liquid
DIARRHEA Gigi Veereman-Wauters • Jan Taminiau
Parents often consult a pediatric gastroenterologist with questions about their child’s stool pattern. Personal and cultural beliefs influence their perception of what may be a problem. Precise questions about the aspect of the child’s defecation pattern and the visual appreciation of a stool sample are important on the first encounter. Normal stool consistency and frequency evolve during childhood. It is commonly accepted that the evacuation of liquid or semiformed stools from 7 times a day to once every 7 days is normal in breast-fed babies. Formula-fed babies have more formed or even harder stools. Colic and cramping are eagerly attributed to difficult defecation. The latest innovations in infant formula are the addition of pre- or probiotics that are intended to favor a bifido-predominant intestinal flora and therefore softer stools.1 Defecation frequency and stool volume decrease from birth to 3 years of age when an “adult” pattern is reached. Infants pass 5 to 10 g/kg/day and adults an average of 100 g/day.2,3 There is an individual variation in what can be considered a normal stool pattern. Healthy toddlers may open their bowels more than three times a day,4 and stool consistency may be loose with identifiable undigested particles.5,6 However, in normal circumstances, intestinal nutrient and water absorption should be sufficient for homeostasis and growth of the organism. If such is not the case, fecal losses cause deficits and disease. In this chapter we discuss the clinical approach to pediatric patients with diarrhea and the differential diagnosis for different age groups. Specific etiologic conditions are discussed in other chapters.
PHYSIOLOGY OF INTESTINAL CONTENT HANDLING In adults, 8 to 10 L of fluid containing 800 mmol sodium, 700 mmol chloride, and 100 mmol potassium enters the proximal small intestine daily.7 Two liters comes from the daily diet, and the remainder from secretions of the salivary glands, stomach, biliary and pancreatic ducts, and proximal small intestine. The small intestine absorbs all but 1.5 L of this amount of fluid containing 200 mmol sodium/L; the colon absorbs all but 100 mL containing approximately 3 mmol sodium of the remaining fluid. Regardless whether a subject ingests a hypotonic meal, such as a steak with an osmolality of 230 mOsm/kg water, or a hypertonic meal, such as milk with a doughnut with an osmolality of 630 mOsm/kg water, the very permeable proximal small intestine allows movement of water and electrolytes into the lumen, rendering the meal isotonic with plasma as it reaches the proximal jejunum. The aforementioned secretions augment the volume of the 300-mL milk-doughnut meal to 1200 mL and the steak -meal from 600 to 2000 mL in the duodenum, and further increases the volume of the milk-doughnut meal to 2000 mL when starches and lactose are digested. In the jejunum, fluids and electrolytes are in equilibrium with plasma, allowing optimal absorption.8,9 106
Water absorption is only possible together with solutes. In the absence of food, all water is absorbed through the neutral NaCl carrier, located mainly in the ileum. This is the so-called sodium-hydrogen exchanger, as the negatively charged anions chloride and bicarbonate are exchanged. With the NaCl carrier a single molecule of sodium co-transports 50 molecules of water. After a meal, the glucose-galactose-sodium carrier (SGLT1), located mainly in the jejunum, transports most sodium and water. One molecule of sodium then co-transports 250 molecules of water.10 All macronutrient transport through the small intestinal epithelium is driven by Na+ transport: amino acids, dipeptides, and fatty acids. The maximal absorption for both the NaCl carrier and the SGLT1 is estimated at 5 to 7 L. After 2 m of small intestinal absorption by the nutrient sodium carriers, the chloride content diminishes, probably suggesting substantial postprandial use of the NaCl carrier.11 In the human colon water absorption is again dependent on Na+ absorption. Na+ is absorbed through an electrogenic process at the apical membrane and maintained by the basolateral Na,K-ATPase, which in each cycle extrudes three Na+ ions for two K+ ions. Another proportionally larger Na+ absorptive mechanism is the electrical neutral Na-Cl absorption in which Na+ is exchanged for H+ and Cl− for bicarbonate. This Na+ absorption is coupled with short-chain fatty acids (SCFAs). The proximal colon contains high luminal concentrations of organic nutrients (nonstarch polysaccharides from plant walls and proteins not absorbed by the small intestine) and high bacterial growth rates parallel high fermentation rates. Of the three SCFAs (acetate, propionate, and butyrate), butyrate is the most abundant and physiologically important. Butyrate serves as a major energy source for colonocytes and plays a crucial role in their growth and differentiation. The butyrate-bicarbonate exchange is the main driving force for Na-Cl absorption, each molecule co-transporting 50 molecules of water. Maximal absorption amounts to 3 to 5 L daily.12 The Na+ absorptive processes are restricted to small intestinal villous cells, whereas Cl− secretory processes are located in the small intestinal crypts. In the colon, Na+ absorption occurs in the crypts; consequently, additional hydraulic forces due to a small neck enlarge Na+ and water absorption enormously.13 This Na+ absorptive state is reversed to a Cl– secretory state under the influence of cAMP or calcium secretagogues. In the small intestine Cl– secretion induced by these secretagogues occurs mainly in the crypts.
DEFINITIONS OF DIARRHEA Feces contain up to 75% water. A relatively small increase in water losses will cause liquid stools. In infants, stool volume in excess of 10 g/kg/day is considered abnormal.3 Diarrhea is the frequent (more than three times a day) evacuation of liquid