Peptic Ulcer Disease (PUD)

Definition

Sites

Aetiology and Pathogenesis

1. Helicobacter pylori

• Responsible for >70% of PUD cases.
• Found in almost all duodenal ulcer patients and ~70-80% of gastric ulcer patients.
• Only 5-10% of infected individuals develop ulcers, implying host and strain-specific cofactors.
• Acts by disrupting the mucus layer, triggering inflammation, and increasing gastric acid output (via gastrin upregulation). - Robbins & Kumar Basic Pathology, p. 589

2. NSAIDs (including aspirin)

• Inhibit COX enzymes, suppressing prostaglandin synthesis, which reduces mucus and bicarbonate secretion and impairs mucosal blood flow.
• Asymptomatic peptic ulceration develops in 10-20% of regular NSAID users; ulcer complications (bleeding, perforation) occur in 1-2% per year. - Katzung's Pharmacology, 16th ed.
• In the US, NSAID-induced gastric ulcers are now becoming the leading cause as H. pylori rates fall and low-dose aspirin use rises in aging populations. - Robbins & Kumar, p. 589

3. Acid hypersecretion

• Duodenal and prepyloric ulcer patients tend to have higher gastric acid levels vs. controls, though the overlap is wide.
• Gastric ulcer patients often have normal acid levels - mucosal defence failure is more relevant.
• Extreme acid hypersecretion (e.g., gastrinoma in Zollinger-Ellison syndrome) causes florid, treatment-resistant ulcers. - Bailey and Love's Surgery, p. 1179

4. Other cofactors

• Cigarette smoking - reduces mucosal blood flow and increases relapse rates.
• Corticosteroids - suppress prostaglandin synthesis, impair healing.
• Alcohol-related cirrhosis, COPD, chronic renal failure, hyperparathyroidism - all increase PUD risk.
• Hypercalcaemia (from hyperparathyroidism or renal failure) stimulates gastrin secretion.
• Robbins & Kumar, p. 589

Endoscopic Appearance

Duodenal ulcer at gastroduodenoscopy - Bailey and Love's Surgery, Fig. 67.10

Benign incisural gastric ulcer at gastroscopy - Bailey and Love's Surgery, Fig. 67.12

Duodenal vs Gastric Ulcer: Key Distinctions

Clinical Features

• Epigastric pain - the cardinal symptom; often described as burning or gnawing.
• Relationship to meals: DU pain classically comes 2-3 hours after eating and at night (relieved by food); GU pain may be precipitated by eating.
• Symptoms are often indistinguishable between DU and GU.
• Examination typically reveals epigastric tenderness; significant findings are absent unless a complication has occurred.
• Bailey and Love's Surgery, p. 1180

Investigations

• Upper GI endoscopy (gastroduodenoscopy) - gold standard; allows biopsy, CLO (Campylobacter-like organism) testing for H. pylori, and assessment of the antrum, pylorus, duodenum, and GOJ.
• H. pylori testing: CLO test (endoscopic biopsy), urea breath test (UBT), or monoclonal stool antigen test for non-invasive detection.
• Barium meal - historical; shows characteristic "niche" sign.
• GU at body or fundus - must biopsy and re-endoscope at 8-12 weeks to confirm healing. DU does not routinely require repeat endoscopy unless symptoms persist.
• Harrison's Principles 22nd ed.; Bailey and Love's Surgery

Treatment

1. H. pylori-associated ulcers

• PPI (twice daily) + clarithromycin 500 mg BD + amoxicillin 1 g BD (or metronidazole 500 mg BD)

• PPI BD + bismuth subsalicylate 524 mg QID + metronidazole 500 mg QID + tetracycline 500 mg QID

• PPI BD + amoxicillin 1 g BD + clarithromycin 500 mg BD + metronidazole 500 mg BD

2. NSAID-associated ulcers

• Discontinue the NSAID if possible; treat with PPI or H2-antagonist.
• If NSAID cannot be stopped, a PPI more reliably promotes healing than an H2-blocker.
• For prevention: daily PPI in patients requiring chronic NSAID/aspirin therapy. - Katzung's Pharmacology 16th ed.

3. Acid suppression agents

• PPIs (omeprazole, esomeprazole, pantoprazole, lansoprazole): render patients virtually achlorhydric; most potent.
• H2-receptor antagonists (ranitidine, famotidine): still effective but less so than PPIs; useful in mild disease or prevention.

4. Lifestyle modification

• Cessation of smoking (reduces mucosal blood flow and increases relapse rate).
• Avoid NSAIDs, limit alcohol.

5. Refractory ulcers

• GU failing to heal after 12 weeks / DU after 8 weeks = refractory.
• Exclude: poor compliance, persistent H. pylori, covert NSAID use, continued smoking.
• Consider ZES or idiopathic acid hypersecretion. Check fasting serum gastrin.
• Harrison's Principles 22nd ed.

Complications

Epidemiology

• Lifetime risk: ~10% in men, ~4% in women.
• More than 4 million Americans treated annually.
• Incidence of H. pylori-related ulcers is declining in developed countries; NSAID-related ulcers are proportionally increasing.
• In developing nations, H. pylori remains the predominant cause. - Robbins & Kumar, p. 589

Recent Evidence

• PMID 38818853 (2024): Endoscopic vs. medical management of peptic ulcers with adherent clots - meta-analysis showing endoscopic therapy reduces rebleeding.
• PMID 40337979 (Cochrane, 2025): PPIs effectively prevent NSAID-induced ulcers and dyspepsia, supporting their use as prophylaxis in high-risk NSAID users.
• PMID 40132025 (2025): Pharmacist-led interventions improve PUD management outcomes.