vasoactive intestinal peptide
Summary
Vasoactive intestinal peptide (VIP) is a neuropeptide secreted by neurons in the GI tract and pancreatic islet delta cells (or non-beta islet cells) that stimulates intestinal water and electrolyte secretion, relaxes GI smooth muscle and sphincters, and dilates blood vessels. Excess VIP secretion, typically from a VIPoma (pancreatic islet cell tumor), causes WDHA syndrome: Watery Diarrhea, Hypokalemia, and Achlorhydria (also called pancreatic cholera or Verner-Morrison syndrome).
Detail
VIP is a 28-amino acid peptide hormone/neurotransmitter structurally related to secretin and glucagon, released by parasympathetic neurons throughout the GI tract and by non-beta islet cells of the pancreas. Physiologically, VIP: (1) stimulates intestinal and pancreatic secretion of water and electrolytes (via increased intracellular cAMP, activating CFTR-mediated Cl- secretion), (2) inhibits gastric acid secretion, (3) relaxes GI smooth muscle including sphincters (lower esophageal sphincter relaxation), and (4) causes vasodilation.
Clinically, VIPomas are rare pancreatic neuroendocrine tumors that secrete excess VIP, producing WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria), also known as Verner-Morrison syndrome or pancreatic cholera. The massive secretory diarrhea persists even with fasting (distinguishing it from osmotic diarrhea), and can lead to severe dehydration, hypokalemia (due to potassium loss in stool), and hypochlorhydria/achlorhydria (VIP inhibits gastric acid secretion). Patients may also have hyperglycemia (VIP has glucagon-like effects) and flushing.
Diagnosis involves elevated serum VIP levels and imaging (CT/MRI) to localize the pancreatic tumor, often with octreotide scan (somatostatin receptor scintigraphy) since these tumors express somatostatin receptors. Treatment includes fluid/electrolyte repletion, octreotide (somatostatin analog) to reduce VIP secretion and diarrhea, and surgical resection of the tumor when localized. VIPomas are associated with MEN1 syndrome in some cases.
High-yield board associations: VIPoma = WDHA syndrome, watery diarrhea despite fasting, hypokalemia, achlorhydria, treat with octreotide.
Sources
- First Aid for the USMLE Step 1
- Guyton and Hall Textbook of Medical Physiology
- Robbins and Cotran Pathologic Basis of Disease
- Goldman-Cecil Medicine
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