What is the mechanism by which H. pylori causes peptic ulcer disease?

Explanation

## Pathogenesis of H. pylori–Induced Peptic Ulcer Disease **Key Point:** H. pylori causes PUD through a dual mechanism: (1) increased gastric acid secretion via ammonia and inflammatory mediators, and (2) impaired mucosal defense through chronic inflammation and reduced bicarbonate production. ### Stepwise Mechanism 1. **Bacterial colonization and ammonia production** - H. pylori produces urease, which hydrolyzes urea to ammonia and CO₂ - Ammonia neutralizes local acid, allowing the bacterium to survive in the acidic environment - Ammonia also stimulates gastrin release from antral G cells → ↑ acid secretion 2. **Chronic inflammation** - Bacterial lipopolysaccharide (LPS) and virulence factors (CagA, VacA) trigger innate and adaptive immune responses - Recruitment of neutrophils, macrophages, and T cells → IL-8, TNF-α, IL-6 production - Inflammation damages the mucosa and reduces mucus and bicarbonate secretion 3. **Reduced mucosal defense** - Decreased mucus layer thickness and quality - Reduced bicarbonate secretion by duodenal mucosa - Impaired epithelial cell regeneration - Loss of protective prostaglandin production 4. **Net result** - Acid-pepsin activity exceeds mucosal defense → ulceration at the gastroduodenal junction ### H. pylori Virulence Factors | Factor | Mechanism | Effect | |--------|-----------|--------| | **Urease** | Ammonia production | Acid neutralization + gastrin stimulation | | **CagA (cytotoxin-associated antigen)** | Type IV secretion system | Epithelial cell damage, IL-8 induction | | **VacA (vacuolating toxin)** | Pore formation in epithelial cells | Cell apoptosis, reduced barrier function | | **Lipopolysaccharide (LPS)** | TLR4 activation | Systemic and local inflammation | **Mnemonic: CHAMP** — **C**agA, **H**yperchlorhydria (↑ acid), **A**mmonia, **M**ucosa damage, **P**rostaglandin loss **Clinical Pearl:** Not all H. pylori-infected individuals develop PUD (~10–20% progress to ulcer disease). Strain virulence (CagA+ strains), host genetic factors (IL-1β polymorphisms), and environmental factors (smoking, NSAIDs) determine progression. **High-Yield:** The "acid is necessary but not sufficient" concept: eradication of H. pylori alone (without acid suppression during initial treatment) can heal ulcers because the inflammatory stimulus is removed. However, acid suppression accelerates healing during the acute phase.