A 64-year-old woman on diclofenac for osteoarthritis presents with epigastric pain and melena. Endoscopy reveals the findings shown in the diagram. The structure marked **A** (multiple shallow erosions) in the gastric antrum is characteristic of NSAID-induced gastropathy. Which of the following best describes the PRIMARY PATHOGENIC MECHANISM underlying these lesions?

Explanation

## Why "Inhibition of COX-1 leading to decreased prostaglandin-mediated mucosal protection and impaired epithelial restitution" is right NSAID-induced gastropathy operates via a dual mechanism: (1) topical injury from acidic NSAIDs, and (2) **systemic inhibition of COX-1**, which produces protective prostaglandins (PGE2, PGI2). These prostaglandins are essential for maintaining mucus secretion, bicarbonate production, mucosal blood flow, and epithelial restitution. The multiple shallow erosions marked **A** result primarily from this COX-1 inhibition, which disrupts the protective mechanisms of the gastric mucosa. This is the dominant systemic mechanism and the reason NSAIDs cause gastropathy even when not in direct contact with the mucosa (ACG Guidelines NSAID Gastropathy 2009). ## Why each distractor is wrong - **"Direct topical caustic injury from acidic NSAID molecules combined with reduced mucus and bicarbonate secretion"**: While topical injury contributes, it is NOT the primary mechanism. NSAIDs cause gastropathy systemically through COX-1 inhibition, not merely through local chemical injury. This option conflates mechanism with consequence. - **"Helicobacter pylori-induced chronic inflammation with secondary NSAID-related ulceration"**: H. pylori is a risk factor that synergizes with NSAIDs, but it is NOT the primary pathogenic mechanism of NSAID gastropathy. Many NSAID ulcers occur in H. pylori-negative patients. The question stem does not indicate H. pylori positivity. - **"Increased gastric acid secretion due to loss of somatostatin-producing D cells in the antral mucosa"**: This is incorrect. NSAIDs do not cause loss of D cells or increase acid secretion as a primary mechanism. In fact, NSAIDs reduce protective factors (prostaglandins) rather than increase acid production. **High-Yield:** NSAID gastropathy = COX-1 inhibition → ↓ PGE2/PGI2 → ↓ mucus, bicarbonate, blood flow, epithelial repair = multiple shallow antral erosions. Test for H. pylori; cover with PPI if NSAID must continue. [cite: ACG Guidelines NSAID Gastropathy 2009; Forrest Classification]