## Pathogenesis of Peptic Ulcer Disease **Key Point:** Peptic ulcer disease results from an imbalance between aggressive factors (acid, pepsin, H. pylori) and defensive factors (mucus, bicarbonate, prostaglandins, blood flow). Increased acid is a hallmark, not decreased acid. ### Aggressive Factors - **Helicobacter pylori infection** — most common cause worldwide; causes chronic active gastritis and mucosal damage [cite:Robbins 10e Ch 17] - **NSAIDs** — inhibit COX-1/COX-2, reducing prostaglandin synthesis and mucosal protection - **Gastric acid hypersecretion** — elevated in Zollinger-Ellison syndrome (gastrin-secreting tumors), leading to severe ulceration - **Pepsin** — proteolytic enzyme that damages mucosa in acidic environment ### Defensive Factors - Mucus layer and bicarbonate secretion - Prostaglandin E2 (PGE2) and prostacyclin — maintain mucosal blood flow and stimulate mucus/bicarbonate secretion - Mucosal blood flow and epithelial regeneration - Trefoil peptides and growth factors (EGF, HGF) **High-Yield:** The pathophysiology is **acid-dependent** — ulcers do not form without acid. Reduced gastric pH and acid secretion would be protective, not causative. Option 4 contradicts fundamental pathophysiology. ### Mechanisms of H. pylori and NSAID Ulcers | Factor | H. pylori Ulcer | NSAID Ulcer | |--------|-----------------|-------------| | Primary mechanism | Chronic inflammation + acid | Reduced mucosal defense | | Gastric acid | Normal or elevated | Normal | | Prostaglandins | Reduced by inflammation | Reduced by COX inhibition | | Location | Antrum > fundus | Antrum and fundus | | Healing | Rapid with eradication therapy | Slow; recurrence if NSAID continued | **Clinical Pearl:** Patients with achlorhydria (absent gastric acid) do not develop peptic ulcers — acid is obligatory for ulcer formation.
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