Malabsorption of Carbohydrates: Lactose Intolerance

230 PHYSIOLOGY CASES AND PROBLEMS Case 40 Malabsorption of Carbohydrates: Lactose Intolerance Candice Nguyen is a 21-year-old student at a prestigious engineering school. During the past 6 months, she experienced several bouts of severe abdominal bloating and cramps, followed by diarrhea. At first, she thought these episodes were caused by the stress of her demanding aca- demic program. However, she noticed that the symptoms occurred approximately 1 hour after she drank milk or ate ice cream. On a visit home, Candice mentioned the symptoms to her mother, who exclaimed, "Don't you know that your father and I have never been able to drink milk?" Candice was examined by her primary care physician, who found her to be in excellent health. Because Candice's symptoms were temporally related to ingestion of dairy products, the physician ordered a lactose-H 2 breath test, which confirmed that Candice has lactose intolerance. Her fecal osmolar gap was measured and was elevated. As further confirmation of the diag- nosis, Candice abstained from dairy products for 1 week and had no episodes of bloating, cramping, or diarrhea. 111/ QUESTIONS 1. How are dietary carbohydrates digested in the gastrointestinal tract? What are the roles of sali- vary, pancreatic, and intestinal mucosal brush border enzymes in carbohydrate digestion? What three monosaccharides are the final products of these digestive steps? 2. How are dietary carbohydrates absorbed from the lumen of the gastrointestinal tract into the blood? Draw a small intestinal epithelial cell that shows the appropriate transporters in the apical and basolateral membranes. 3. Describe the steps involved in the digestion and absorption of lactose. 4. Propose a mechanism for Candice's lactose intolerance. 5. Why did her lactose intolerance cause diarrhea? 6. Candice's lactose-H2 breath test (which involves measuring H2 gas in the breath after ingesting 50 g lactose) was positive. Why? 7. What is the fecal osmolar gap? Why was Candice's fecal osmolar gap elevated? 8. What treatment was recommended? 232 PHYSIOLOGY CASES AND PROBLEMS 9 ANSWERS AND EXPLANATIONS 1. Dietary carbohydrates include starch, disaccharides, monosaccharides, and cellulose (which is indigestible). Of these, only monosaccharides (glucose, galactose, and fructose) are absorbable. Thus, to be absorbed, starches and disaccharides must first be digested to glucose, galactose, or fructose (Figure 5-1). Starch (Y. - Amylase 1 / Disaccharides a -Dextrins Maltose Maltotriose Trehalose Lactose Sucrose I Lactase 1 1 I I 'I' 1 1 Monosaccharides Glucose Glucose Glucose Galactose Glucose Fructose Figure 5-1 Digestion of carbohydrates in the gastrointestinal tract. Starch is digested to disaccharides (a-dextrins, maltose, and maltotriose) by a-amylase in saliva and pancreatic secretions. Other disaccharides, present in the diet, include trehalose, lactose, and sucrose. Thus, disaccharides are either produced from the digestion of starch or are ingested in food. These disaccharides are then digested to monosaccharides by enzymes located in the brush border of intestinal mucosal cells. a-Dextrins, maltose, and maltotriose are digested to glucose by a-dextrinase, maltase, and sucrase, respectively. Trehalose is digested to glucose by trehelase. Lactose is digested to glucose and galactose by lactase. Sucrose is digested to glucose and fructose by sucrase. Thus, the three monosaccharide products of all these digestive steps are glucose, galactose, and fructose. 2. Monosaccharides are the only absorbable form of carbohydrates. Figure 5-2 shows a small intestinal epithelial cell with its apical membrane facing the lumen of the intestine and its basolateral membrane facing the blood. Absorption of monosaccharides is a two-step process involv- ing (1) transport across the apical membrane and (2) subsequent transport across the basolateral membrane. In this regard, glucose and galactose are processed somewhat differently from fructose, as follows. Glucose and galactose enter the cell across the apical membrane by Nal-- dependent cotransport mechanisms (Na +-glucose and Na 4 -galactose cotransporters). These Nat-dependent cotransporters, which are secondary active transport, are energized (driven) by the Na + gradient across the apical cell membrane. (This Na' gradient is maintained by Na--K+ ATPase that is located in the basolateral membrane.) Glucose and galactose then exit the cell across the basolateral membrane by facilitated diffusion. In contrast, fructose enters and exits the cell by facilitated diffusion. GASTROINTESTINAL PHYSIOLOGY 233 Epithelial cell of small intestine Lumen Blood Na+ K+ Na+ Glucose Glucose Na+ Galactose Galactose 10- Fructose Fructose Apical Basolateral membrane membrane Figure 5-2 Absorption of monosaccharides by epithelial cells in the small intestine. 3. The steps in the digestion and absorption of lactose are given in the answers to the previous questions. Lactose (a dietary disaccharide that is present in dairy products) is digested by lactase (a brush border enzyme) to glucose and galactose. Glucose and galactose are then absorbed by the two-step process described in Question 2: Na t -dependent cotransport across the apical membrane followed by facilitated diffusion across the basolateral membrane. 4. Lactose cannot be absorbed by intestinal epithelial cells. As a disaccharide, it must first be digested to the absorbable monosaccharides glucose and galactose. Thus, lactose intolerance can result from a defect in lactose digestion to monosaccharides (e.g., lactase deficiency) or from a defect in one of the monosaccharide transporters. Note, however, that a defect in the glucose or galactose transporter would create nonspecific intolerance to di- and monosaccharides. Can- dice has lactase deficiency (either too little lactase or none at all). Because of this deficiency, she cannot digest dietary lactose in milk products to the absorbable monosaccharides glucose and galactose. 5. Lactose intolerance causes diarrhea because undigested lactose is not absorbed. Some of the lactose is fermented by colonic bacteria to lactic acid, methane, and H2 gas. Undigested lactose and lactic acid then behave as osmotically active solutes in the lumen of the gastrointestinal tract. These solutes draw water isosmotically into the intestinal lumen and produce osmotic diarrhea. (When lactose is digested normally to glucose and galactose, these osmotically active monosaccharides are absorbed and, thus, do not remain in the lumen of the gastrointestinal tract.) 6. Candice's lactose-H 2 breath test was positive because undigested lactose in the lumen of the gastrointestinal tract was fermented by colonic bacteria. A byproduct of this fermentation (H2 gas) was absorbed into the bloodstream, expired by the lungs, and then detected in the test. 234 PHYSIOLOGY CASES AND PROBLEMS 7. The fecal osmolar gap may be an unfamiliar term that refers to unmeasured solutes in the feces. The concept can be useful in understanding the pathophysiology of diarrhea. The test measures the total osmolarity and the Na + and K+ concentrations of a stool sample. The sum of the Na+ and IC+ concentrations are multiplied by two to account for the balancing anions (usually Cl- and HCO3-) that must accompany these cations. The difference between total fecal osmolarity and the sum of two times the fecal Na+ and K* concentrations is the fecal osmolar gap. The fecal osmolar gap represents unmeasured fecal solutes. Candice's fecal osmolar gap was elevated because unabsorbed lactose contributed to the total osmolarity of the stool. 8. Candice's treatment is simple. If she avoids dairy products that contain lactose, no unabsorbed lactose will accumulate in the lumen of her gastrointestinal tract. If she does not want to elim- inate dairy products from her diet, she can take lactase tablets, which will substitute for the missing brush border enzyme. Key topics Digestion of carbohydrates Facilitated diffusion Fecal osmolar gap Lactase Lactose intolerance Na--galactose cotransport Na '-glucose cotransport Osmotic diarrhea Secondary active transport.

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