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 academic 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 diagnosis, 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 salivary, 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
Monosaccharides
Glucose
'I'
1
1
I
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 involving (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
Na t -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
Lumen
Epithelial cell of small intestine
Blood
Na+
K+
Na+
Glucose
Glucose
Na+
Galactose
Galactose
Fructose
10- Fructose
Apical
membrane
Basolateral
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. Candice 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 eliminate 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