A 48-year-old woman with Zollinger-Ellison syndrome (gastrinoma) presents with severe peptic ulcer disease. Her serum gastrin level is 850 pg/mL (normal <100). Which of the following mechanisms best explains her elevated gastric acid output?

Explanation

## Zollinger-Ellison Syndrome and Gastric Acid Hypersecretion ### Pathophysiology of ZES: **Key Point:** Gastrinoma (ectopic gastrin-secreting tumor) produces unregulated gastrin that continuously stimulates parietal cells and ECL cells, bypassing normal negative feedback mechanisms. ### Why Continuous Gastrin Stimulation Bypasses Normal Regulation: 1. **Normal feedback:** High acid (low pH) → increased somatostatin → inhibits gastrin release from G cells 2. **In ZES:** Gastrin comes from tumor, NOT G cells → somatostatin cannot suppress tumor gastrin production 3. **Result:** Continuous parietal cell stimulation → maximal acid output → severe ulceration ### The Cascade in ZES: - Ectopic gastrin (850 pg/mL) → stimulates parietal cells directly via CCK-B receptors - Ectopic gastrin → stimulates ECL cells → histamine release → H2 receptors on parietal cells - Both pathways are continuously active and not suppressed by normal feedback **Clinical Pearl:** In ZES, the basal acid output is often >15 mEq/hour (normal <5), and the ratio of basal to stimulated acid output is >0.6 (normally <0.4), indicating autonomous acid secretion. **High-Yield:** ZES = Tumor gastrin bypasses negative feedback → continuous parietal cell stimulation → severe acid hypersecretion