A patient develops a VIPoma secreting vasoactive intestinal peptide. Which physiological mechanism explains the profuse watery diarrhea (>3 L/day) in this condition?

• A VIP increases intestinal adenylyl cyclase activity → cAMP → CFTR chloride secretion, while inhibiting electroneutral NaCl absorption ✓
• B VIP stimulates CCK-mediated pancreatic enzyme secretion causing osmotic diarrhea
• C VIP activates intestinal smooth muscle via IP3, causing hypermotility and reduced absorption time
• D VIP competitively inhibits sodium-glucose linked transporter (SGLT1) causing malabsorptive diarrhea

Explanation

VIP acts on intestinal crypt cells via adenylyl cyclase (Gs-coupled VIP receptor) to increase cAMP, which activates protein kinase A. This phosphorylates and opens CFTR chloride channels in crypt cells, driving Cl- secretion into the lumen, followed by Na+ and water. Simultaneously, VIP inhibits electroneutral NaCl absorption in villus cells. The net result is massive isotonic fluid secretion — the hallmark of secretory diarrhea (persists with fasting). VIP does not stimulate CCK or SGLT1 inhibition; its primary mechanism is cAMP-mediated secretion, not motility-driven.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.