A 58-year-old woman with chronic knee pain takes naproxen daily and presents with melena. Endoscopy shows a gastric body ulcer. The earliest physiological defect produced by NSAIDs that predisposes to this lesion is:

• A Loss of the H-K-ATPase pump leading to achlorhydria
• B Reduced prostaglandin mediated secretion of mucus and bicarbonate by surface epithelial cells ✓
• C Impaired tight junction integrity due to reduced claudin expression
• D Excess somatostatin release suppressing protective hyperaemia

Explanation

NSAIDs inhibit cyclooxygenase 1, lowering mucosal prostaglandin E2 and prostacyclin. These prostaglandins normally stimulate surface epithelial cells to secrete mucus and bicarbonate, maintain mucosal blood flow, and support epithelial restitution. Their loss strips the pre-epithelial defence first, allowing acid back diffusion. Acid secretion is not reduced by NSAIDs, and the initial lesion is not a tight junction disorder or a hormonal excess state.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.