A 58-year-old man with osteoarthritis of the knee has been taking NSAIDs regularly for 6 months. He now presents with epigastric pain and melena. Upper GI endoscopy reveals a gastric ulcer. Which is the most common site of NSAID-induced gastrointestinal ulceration?

Explanation

## Most Common Site of NSAID-Induced GI Ulceration ### Anatomical Distribution **Key Point:** The **gastric antrum** is the most common site of NSAID-induced gastric ulceration, accounting for the majority of NSAID-related gastric ulcers. This is well-established in standard pharmacology and gastroenterology references (KD Tripathi, Harrison's Principles of Internal Medicine). ### Why the Gastric Antrum? 1. **Prostaglandin dependence**: NSAIDs inhibit COX-1, depleting cytoprotective prostaglandins (PGE₂, PGI₂). The antral mucosa is highly dependent on prostaglandin-mediated bicarbonate and mucus secretion for protection against luminal acid and pepsin. 2. **Acid-pepsin exposure**: The antrum is the transitional zone where gastric acid and pepsin are concentrated before gastric emptying, making it particularly vulnerable when mucosal defenses are compromised. 3. **Mucosal vulnerability**: With COX-1 inhibition, reduced mucus and bicarbonate secretion in the antrum allows back-diffusion of H⁺ ions, leading to mucosal injury and ulceration. ### Comparison of NSAID Ulcer Sites | Site | Frequency | Notes | |------|-----------|-------| | **Gastric antrum** | **Most common** | **Primary site of NSAID-induced ulcers** | | Duodenum | Second most common | Acid-peptic mechanism | | Gastric body / greater curvature | Less common | More typical of stress ulcers | | Pyloric region | Uncommon | Rare in isolation | ### Clinical Pearl **Clinical Pearl:** NSAID-induced gastric ulcers most commonly occur in the **antrum**, whereas *H. pylori*-associated ulcers favour the antrum and lesser curvature via a different (inflammatory/urease-mediated) mechanism. Duodenal ulcers are more strongly associated with *H. pylori* than with NSAIDs alone. At endoscopy, multiple antral erosions/ulcers in an NSAID user without *H. pylori* infection strongly suggest NSAID gastropathy. ### High-Yield Risk Factors for NSAID Ulceration **High-Yield:** Age >65 years, concurrent corticosteroid or anticoagulant use, high-dose or long-term NSAID therapy, prior peptic ulcer disease, and absence of PPI co-therapy significantly increase the risk of NSAID-induced ulceration. [cite: KD Tripathi 8e Ch 12; Harrison's Principles of Internal Medicine 20e Ch 317]