Peptic Ulcer Disease: Stepwise Pathogenesis from Acid–Mucosal Defense Imbalance

Step 1: Normal Stomach (Balanced State) Gastric acid (HCl) is produced by parietal cells. Mucosal defenses maintain integrity: Mucus layer Bicarbonate secretion Adequate mucosal blood flow Prostaglandins (PGE₂) Result: Intact gastric and duodenal mucosa; no ulcer. Step 2: Imbalance Occurs → Ulcer Formation Ulcer forms when: Acid is excessive, or Mucosal protection is weakened Step 3: Pathways Leading to Ulcer A. H. pylori Pathway (Increased Acid / Impaired Defense) H. pylori infects gastric mucosa → inflammation Mechanisms: ↑ Gastrin → ↑ Acid → duodenal mucosal injury Impaired mucus and bicarbonate locally Typical location: Duodenum > Stomach Symptoms: Often present before complications (epigastric pain) Treatment: PPI + Antibiotics (10–14 days) B. NSAID Pathway (Decreased Protection) NSAIDs inhibit cyclooxygenase → ↓ prostaglandins Consequences: ↓ Mucus & bicarbonate ↓ mucosal blood flow → weak barrier Typical location: Stomach > Duodenum Symptoms: Often silent; may first appear as bleeding or perforation Treatment: PPI alone (8–12 weeks) Step 4: Outcome Persistent imbalance → Peptic ulcer formation Possible complications: bleeding, perforation, obstruction