Which pathogenic mechanism is responsible for NSAID-induced peptic ulcer disease?

Question

Accepted Answer

A. Inhibition of prostaglandin synthesis leading to reduced mucosal protection and bicarbonate secretion. ## Pathogenesis of NSAID-Induced Peptic Ulcer Disease

**Key Point:** NSAIDs cause peptic ulcers primarily by inhibiting COX-1 and COX-2, which reduces prostaglandin (PG) synthesis. Prostaglandins are essential for mucosal cytoprotection, and their depletion leads to ulcer formation.

### Mechanism of Mucosal Injury

1. **COX inhibition**: NSAIDs block both COX-1 and COX-2 enzymes.
2. **Prostaglandin depletion**: Reduced synthesis of PGE~2~ and PGI~2~.
3. **Loss of protective functions**:
   - Decreased mucus secretion
   - Reduced bicarbonate secretion
   - Impaired mucosal blood flow
   - Weakened epithelial cell tight junctions
4. **Net result**: Increased acid-induced mucosal damage and ulcer formation.

### Prostaglandin Functions in Mucosal Protection

| Function | Effect |
| --- | --- |
| Mucus secretion | Creates protective barrier |
| Bicarbonate secretion | Neutralizes acid at mucosal surface |
| Blood flow | Maintains mucosal perfusion and healing |
| Cell proliferation | Supports epithelial regeneration |
| Tight junction integrity | Prevents back-diffusion of acid |

**Clinical Pearl:** This is why COX-2 selective inhibitors (e.g., celecoxib) were developed — they spare COX-1 in the stomach, preserving prostaglandin-mediated cytoprotection. However, they still carry ulcer risk, albeit lower than non-selective NSAIDs.

**High-Yield:** NSAID ulcers are typically **gastric** (especially antral) and **duodenal**, and are often **asymptomatic** until complications (bleeding, perforation) occur. This contrasts with H. pylori ulcers, which are usually symptomatic.

**Mnemonic:** **"PG DOWN = Ulcer UP"** — Prostaglandins down → ulcer risk up.

![Peptic Ulcer Disease diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2966.webp)

Answer

B. Increased Helicobacter pylori colonization due to altered gastric pH

Answer

C. Increased gastric acid secretion via COX-1 inhibition in parietal cells

Answer

D. Direct mucosal injury from NSAID crystals deposited in the gastric epithelium

Which pathogenic mechanism is responsible for NSAID-induced peptic ulcer disease?

Explanation

Pathogenesis of NSAID-Induced Peptic Ulcer Disease

Mechanism of Mucosal Injury

Prostaglandin Functions in Mucosal Protection

Practice similar questions

Join our NEET PG community

Function	Effect
Mucus secretion	Creates protective barrier
Bicarbonate secretion	Neutralizes acid at mucosal surface
Blood flow	Maintains mucosal perfusion and healing
Cell proliferation	Supports epithelial regeneration
Tight junction integrity	Prevents back-diffusion of acid