Download CASE 32

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CASE 32
A 17-year-old boy presents to his primary care physician with complaints of
diarrhea for the last 2 days. The patient states that he just returned to the
United States after visiting relatives in Mexico. The diarrhea began suddenly
and is described as “water.” He has noticed no abdominal pain or blood in his
stool. On examination, he appears dehydrated, but otherwise his physical
examination is normal. His stool is examined and appears like “rice water.”
The patient is diagnosed with an infectious form of diarrhea, most likely due
to Vibrio cholerae.
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What location in the gastrointestinal (GI) tract has tight, or
impermeable, junctions between the epithelial cells?
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Why do patients with diarrhea often have hypokalemia?
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How does V. cholerae cause diarrhea?
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CASE FILES: PHYSIOLOGY
ANSWERS TO CASE 32: INTESTINAL WATER AND
ELECTROLYTE TRANSPORT
Summary: A 17-year-old boy has profuse watery diarrhea from a V. cholerae
infection.
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Location of impermeable gap junctions: Large intestine.
Hypokalemia with diarrhea: Intestinal secretions are enriched in
potassium, and so there is increased loss with diarrhea.
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V. cholerae and diarrhea: Toxin binds to receptors on apical
membrane of crypt cells and activates adenylate cyclase, which
increases intracellular cyclic adenosine monophosphate (cAMP) and
secretion of chloride. Both sodium and water follow the chloride into
the lumen and result in the secretory diarrhea.
CLINICAL CORRELATION
Diarrhea can be seen in a variety of conditions and disease processes. There
are four basic mechanisms that result in diarrhea: osmotic (lactose intolerance), exudative disorders (inflammatory bowel disease), secretory (V. cholerae),
and motility disturbance (hyperthyroidism). Diarrhea from cholera has a rapid
onset and can lead to progressive dehydration and even death. The incubation
period is about 24 to 48 hours, after which the patient will begin having painless watery diarrhea. The diarrhea is free from blood and appears like rice
water. Patients often complain of muscle cramps that result from electrolyte
abnormalities. Complications are a result of the fluid loss and electrolyte
abnormalities. When patients are adequately hydrated and electrolytes are
replaced, the process is self-limiting and resolves in a few days. The diagnosis can be confirmed by the identification of V. cholerae in stool.
APPROACH TO WATER ABSORPTION
Objectives
1.
2.
Discuss sodium and water absorption and secretion in the small intestine and colon.
Describe potassium, chloride, and bicarbonate absorption and secretion in the small intestine and colon.
DISCUSSION
Approximately 9 L of water and 30 g of sodium are absorbed from the
small intestine and colon each day, but only about 2 L of water and 5 g of
sodium are ingested. The difference between absorbed and ingested values is
CLINICAL CASES
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because of salivary, gastric, pancreatic, biliary, and intestinal secretions, which
then are reabsorbed. The vast majority of this fluid is absorbed by the small
intestine, with only about 1 to 2 L being absorbed from the colon.
Normally, only about 0.1 to 0.2 L is excreted in the feces.
Throughout the GI tract, water permeates membranes passively to maintain isosmotic conditions (except for salivary secretions, which are hypotonic,
and colonic contents, which are hypertonic) as solutes are actively secreted and
absorbed. Salivary glands, the stomach, the pancreas, and the liver are mainly
secretory organs, as discussed in Case 30. The intestine, in contrast, has both
secretory and absorptive functions. Under normal conditions, absorption
dominates, but as in this case, that is not always the case. The mechanisms
involved in small intestinal absorption of the products of digestion are covered
in Case 31. This absorption, which is accompanied by significant amounts of
sodium, chloride, and water, is accomplished by villus epithelial cells.
Intestinal secretion, by contrast, is accomplished by crypt epithelial cells.
There are multiple pathways and mechanisms by which sodium is absorbed
by villus cells of the intestine. The major ones are the sodium-coupled absorption of sugars and amino acids, sodium-chloride cotransport, sodium-hydrogen
countertransport, and the entry of sodium by restricted diffusion. All these are
secondary active processes that are “powered” by the sodium-potassium
ATPase located on the basolateral borders of the villus cells. With this absorption comes the passive absorption of anions, mostly chloride, and water.
Potassium is absorbed by both passive and active processes. In the small intestine, potassium is concentrated in the chyme as sodium and water are absorbed,
but because the paracellular pathways are “leaky,” potassium is absorbed passively down its electrochemical gradient. In the colon, which is less leaky,
potassium is absorbed through a primary active process involving a potassiumhydrogen ATPase. Potassium also is secreted actively by colonic villus cells
because of the restricted diffusion of potassium through apical membrane channels. Thus, as sodium is absorbed, potassium is lost. The net result is that fecal
fluid has a relatively high potassium concentration. The situation with bicarbonate is also complicated. Most of the secreted bicarbonate acts to neutralize
the acid secreted by the stomach. This results in no net loss or gain of bicarbonate because the secretion of acid involves the production of bicarbonate to
balance that which is secreted by the pancreas and liver. In the distal small
intestine and colon, bicarbonate is secreted in exchange for chloride through the
action of a chloride-bicarbonate countertransporter on the apical membrane of
villus cells. Thus, fecal secretions tend to be alkaline.
There normally is a low level of secretion of sodium, chloride, and water
by crypt epithelial cells of the small intestine because of the secondary
active transport of chloride. A sodium-potassium-chloride cotransporter is
located on the basolateral surface of these cells (see Figure 32-1). Thus, the
movement of sodium down its electrochemical gradient facilitates the uptake of
chloride. This chloride then exits the apical membrane down its electrochemical gradient by restricted diffusion through a chloride channel. Sodium and
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CASE FILES: PHYSIOLOGY
Lumen
Interstitium
CI−
K+
∼
CI−
Na+
Na+ (K+)
CI−(CI−)
Na+
Na+
Figure 32-1. Crypt cells of the intestine. Cl− is secreted by a secondary active
process.
water follow passively through paracellular pathways. The fluid secreted by
these cells helps maintain the liquidity of the intestinal contents and aids in
digestion and absorption. The activity of the chloride channel is regulated by
both calcium and cAMP. Elevations of either caused by actions of neurotransmitters, or in this case toxins, increase flux through the channels and result
in an increase in secretion. This secretion can exceed the ability of the villus
cells to absorb, thus resulting in diarrhea rich in volume, potassium, and bicarbonate. Fortunately, the absorptive abilities of the villus cells are large and can
be maximized by orally administering fluids that are rich in sodium and glucose. This is the basis for the oral rehydration (replacement) therapies that have
been so successful in decreasing mortality from secretory diarrhea.
COMPREHENSION QUESTIONS
[32.1]
Oral rehydration formulas are noted to facilitate the absorption of
sodium chloride and water. This observation is due in particular
because of the inclusion of which of the following?
A.
B.
C.
D.
E.
Bile salts
Other chloride salts
Carbohydrates
Fatty acids
Proteins
CLINICAL CASES
[32.2]
Which of the following is the rank order, from greatest to least, of
areas of water absorption in the GI tract in a normal individual?
A.
B.
C.
D.
E.
[32.3]
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Colon, small intestine, stomach
Colon, stomach, small intestine
Small intestine, colon, stomach
Small intestine, stomach, colon
Stomach, small intestine, colon
Patients with cystic fibrosis have a defect in apical chloride channels
in many epithelial cells. Such patients have a major defect in which
of the following?
A.
B.
C.
D.
E.
Colonic sodium chloride and water absorption
Gastric acid secretion
Ileal bile acid absorption
Jejunal glucose absorption
Small intestinal sodium chloride and water secretion
Answers
[32.1]
C. Owing to the presence of sodium-coupled glucose transporters in
intestinal epithelial cells, sodium and water absorption are greatly
enhanced by the inclusion of carbohydrates. Although amino acid and
bile salt absorption also are sodium coupled, those transporters are
not as abundant. Absorption of fatty acids is not sodium coupled.
[32.2]
C. By far, the greatest volume of intestinal contents is absorbed by
the small intestine. The volume absorbed by the colon is significant
and can increase when the functioning of the small intestine is
impaired. However, the volume absorbed is much less than in the
small intestine. The stomach absorbs little, if any, water. It mostly is
a secretory organ.
[32.3]
E. Sodium, potassium, and chloride are transported actively into
intestinal crypt cells across their basolateral borders. Chloride then
exits the cells down its electrochemical gradient through apical chloride channels. These channels are defective in cystic fibrosis. HCl
secretion by the gastric parietal cells does not involve these chloride
channels. Also, the chloride that is absorbed along with sodium in the
small intestine and large intestine does not pass through these channels. Bile acids are anions at the pH existing in the ileum and are not
associated with chloride absorption.
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CASE FILES: PHYSIOLOGY
PHYSIOLOGY PEARLS
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Water absorption and secretion in the intestine are passive and are
driven by the absorption and secretion of solutes.
Small intestinal villus epithelial cells absorb sodium and water; villus
crypt cells secrete sodium and water.
The majority of water absorption takes place in the proximal small
intestine and is isosmotic.
Sodium absorption in the ileum and colon is partially regulated by
aldosterone.
If bile salts are not absorbed in the ileum and pass into the colon,
they increase secretion of electrolytes and water by the colon.
Loss of gastric contents by vomiting results in alkalosis because of
loss of hydrochloric acid. Diarrhea results in acidosis because of
loss of bicarbonate.
REFERENCES
Johnson LR. Intestinal electrolyte and water transport. In: Johnson LR, ed. Essential
Medical Physiology. 3rd ed. San Diego, CA: Elsevier Academic Press;
2003:547-555.
Johnson LR. Fluid and electrolyte absorption. In: Johnson LR, ed. Gastrointestinal
Physiology. 7th ed. Philadelphia, PA: Mosby; 2007:127-135.
Kutchai HC. Digestive system. In: Levy MN, Koeppen BM, and Stanton BA, eds.
Berne & Levy, Principles of Physiology. 4th ed. Philadelphia, PA: Mosby;
2006:429-494.