Chapter 25. Overview of Gastrointestinal Function & Regulation
Following a natural disaster in Haiti, there is an outbreak of cholera among displaced persons living in a tent encampment. The affected individuals display severe diarrheal symptoms because of which of the following changes in intestinal transport?
A. Increased K+–Cl− cotransport in the small intestine
B. Decreased K+ secretion into the colon
C. Increased K+ absorption in the crypts of Lieberkühn
D. Increased Na+ absorption in the small intestine
E. Increased Cl− secretion into the intestinal lumen
The correct answer is E. The active (A) subunit of cholera toxin is internalized by intestinal epithelial cells and causes an irreversible increase in intracellular cAMP, which in turn activates intestinal chloride secretion driving fluid accumulation in the lumen. cAMP also activates ENaC activity thereby stimulating Na+ absorption, but this mechanism only exists in the distal colon; furthermore, electroneutral NaCl absorption in the small intestine is inhibited rather than stimulated by cAMP (rules out option D). Similarly, basolateral K+–Cl− cotransport contributes to electroneutral NaCl absorption, but would be reduced rather than increased in the setting of cholera (rules out option A). Finally, neither secretion nor absorption of K+ ions is of large enough magnitude to account for the marked fluid loss seen in cholera, nor are the direction of effects stated consistent with luminal fluid accumulation and thus diarrhea (rules out options B and C).
A 50-year-old man comes to see his clinician complaining of severe epigastric pain, frequent heartburn, and unexplained weight loss of 20 lb over a 6-month period. He claims to have obtained no relief from over-the-counter H2 antihistamine drugs. He is referred to a gastroenterologist, and upper endoscopy reveals erosions and ulcerations in the proximal duodenum and an increased output of gastric acid in the fasting state. The patient is most likely to have a tumor secreting which of the following hormones?
The correct answer is D. Zollinger–Ellison syndrome, with increased gastric acid secretion even in the absence of signals triggered by ingestion of a meal, is caused by a secreting gastrinoma. The uncontrolled increase in circulating gastrin markedly upregulates gastric secretion, which overcomes normal defensive mechanisms and leads to mucosal injury. Somatostatin inhibits rather than stimulates gastric secretion, and thus the clinical picture is not consistent ...