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Review Question - QID 212438

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QID 212438 (Type "212438" in App Search)
A 24-year-old man presents to his primary care provider with complaints of 2 days of profuse diarrhea. He states that his stool started to turn watery and lighter in color beginning yesterday, and he has not noticed any fevers. His diarrhea episodes have become more frequent and white-colored over the past day. He has also noticed dry mouth symptoms and darker urine today. He is otherwise healthy but recently returned from a trip with friends to South Asia. None of his friends have reported any symptoms. On exam, his temperature is 98.6°F (37.0°C), blood pressure is 110/68 mmHg, pulse is 80/min, respirations are 14/min. The patient has normal skin turgor, but he has noticeably dry oral mucosa and chapped lips. The patient has dull abdominal aching but no tenderness to palpation. The stool is found to contain large quantities of comma-shaped organisms. Fecal occult blood testing is negative and no steatorrhea is found. The provider recommends immediate oral rehydration therapy. Which of the following is the likely mechanism of this patient’s diarrhea?

Decreased cyclic AMP

1%

1/90

Increased cyclic AMP

89%

80/90

Increased cyclic GMP

3%

3/90

Inhibition of protein synthesis

0%

0/90

Shortening of intestinal villi

2%

2/90

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This patient with comma-shaped organisms producing a profuse, watery diarrhea is likely infected by Vibrio cholerae. Cholera toxin binds to the G protein subunit, which increases cyclic AMP.

Vibrio cholerae is a gram-negative, oxidase-positive, comma-shaped bacteria that is endemic to many low- to middle-income countries around the world. V. cholerae produces cholera toxin, which activates the Gs alpha subunit of the G protein which activates adenylate cyclase. This leads to increased cyclic AMP and eventually the secretion of sodium, potassium, bicarbonate, and water into the intestinal lumen. This produces a profuse diarrhea often termed “rice-water diarrhea” that requires oral rehydration therapy. Of note, heat-labile enterotoxin produced by enterotoxigenic E. coli have a similar mechanism. This toxin stimulates the Gs alpha subunit, which activates adenylate cyclase and also increases cyclic AMP.

Incorrect Answers:
Answer 1: Decreased cyclic AMP is not the mechanism of cholera toxin. By activating the Gs alpha subunit, cholera toxin increases cyclic AMP production.

Answer 3: Increased cyclic GMP is not the mechanism of cholera toxin. Heat-stable enterotoxin produced by enterotoxigenic E. coli binds to guanylate cyclase to increase cyclic GMP. This also results in a watery diarrhea.

Answer 4: Inhibition of protein synthesis is the mechanism of action of Shiga toxins, which are produced by Shigella dystenteriae. Bacillary dysentery caused by Shigella results in a bloody diarrhea.

Answer 5: Shortening of intestinal villi is the mechanism of action of enteropathogenic E. coli (EPEC). EPEC adheres to the intestinal villi, which deforms the actin cytoskeleton of the cells and leads to a blunting of the intestinal villi. EPEC usually causes diarrhea in children.

Bullet Summary:
Vibrio cholerae results in a rice-water diarrhea as a result of cholera toxin binding the Gs alpha subunit, activating adenylate cyclase and increasing cyclic AMP production.

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