Gastroenterology
Peptic Ulcer Disease
H. pylori, NSAIDs, and the breakdown of mucosal defenses
Peptic ulcer disease (PUD) is mucosal erosion deeper than 5 mm in stomach (gastric ulcer) or duodenum (duodenal ulcer, more common). Two dominant causes — H. pylori infection (causing 70-80% of duodenal and 60% of gastric ulcers) and NSAIDs (15-30% of ulcers). Other causes: Zollinger-Ellison syndrome, stress ulcers in critical illness, smoking, and rare etiologies. Pathophysiology centers on imbalance between aggressive factors (acid, pepsin, H. pylori) and defenses (mucus, bicarbonate, prostaglandins, blood flow). Complications: bleeding (15%), perforation (7%), gastric outlet obstruction. Treatment: PPIs, H. pylori eradication, NSAID cessation. Marshall and Warren's 1982 discovery of H. pylori revolutionized the field — earned 2005 Nobel Prize.
- H. pylori prevalence~50% global, ~30% US adults
- NSAID risk4x ulcer risk; aspirin even at 81 mg
- Triple therapyPPI + clarithromycin + amoxicillin × 14 days
- PPI examplesOmeprazole, pantoprazole, esomeprazole
- Bleeding mortality5-10% in severe upper GI bleeds
- DiscoveredH. pylori — Marshall & Warren, 1982
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Why peptic ulcer disease matters
- Common GI complaint. 5-10% lifetime prevalence; major source of dyspepsia.
- Bleeding ulcers. Leading cause of upper GI bleeding; mortality 5-10%.
- NSAID prescribing. Co-prescribe PPI in high-risk patients to prevent ulcers.
- H. pylori eradication. Reduces ulcer recurrence and gastric cancer risk.
- Cancer screening. Gastric ulcers require biopsy to exclude adenocarcinoma.
- Critical care. Stress ulcer prophylaxis is standard in ICU.
- Antibiotic stewardship. Rising clarithromycin resistance changes treatment regimens.
Common misconceptions
- Stress causes ulcers. Psychological stress alone doesn't cause PUD; H. pylori and NSAIDs do.
- Spicy food causes ulcers. No causal evidence; can aggravate existing symptoms.
- Ulcers cause acid reflux. Different conditions; ulcers cause epigastric pain, not heartburn.
- PPI is benign long-term. Linked to fractures, B12, magnesium, and infection risks; deprescribe when possible.
- All ulcers heal with PPI. Without H. pylori eradication or NSAID cessation, recurrence is high.
- Gastric ulcer = duodenal ulcer. Gastric needs biopsy and follow-up to rule out cancer; duodenal almost never malignant.
Frequently asked questions
How does H. pylori cause ulcers?
Helicobacter pylori is a gram-negative spiral bacterium that survives stomach acid by producing urease, which converts urea to ammonia, neutralizing local pH. It burrows under the mucus layer, attaches to gastric epithelium, and induces inflammation via cag-PAI virulence factors and VacA toxin. Chronic inflammation causes hypergastrinemia, increased acid secretion (especially in antral-predominant gastritis), and impaired mucosal defense. Eradication heals ulcers and prevents recurrence.
How do NSAIDs cause ulcers?
NSAIDs inhibit COX-1 in gastric mucosa, blocking synthesis of protective prostaglandins (PGE2, PGI2) that normally maintain mucus, bicarbonate, blood flow, and epithelial regeneration. Without prostaglandins, even normal acid damages mucosa. Risk factors: age > 65, prior ulcer, anticoagulants, corticosteroids, high dose, long duration. Risk persists with low-dose aspirin (81 mg). Mitigation: COX-2 selective NSAIDs (celecoxib, lower GI risk but higher CV risk), co-prescribe PPI, eradicate H. pylori first.
How do PPIs work?
Proton pump inhibitors irreversibly bind H+/K+ ATPase (the proton pump) on gastric parietal cells — the final common step in acid secretion. Suppress acid 90%+ for 24-48 hours. Best taken 30-60 minutes before meals when proton pumps are active. Examples: omeprazole 20-40 mg, pantoprazole 40 mg, esomeprazole 20-40 mg. Long-term risks: B12 deficiency, hypomagnesemia, osteoporotic fractures, C. difficile, possibly dementia (controversial).
How is H. pylori diagnosed and treated?
Tests: urea breath test (active infection, ~95% sensitive/specific), stool antigen, biopsy with rapid urease test or histology, serology (less specific — can't distinguish active from past infection). Treat with quadruple therapy (bismuth, PPI, tetracycline, metronidazole × 14 days) or PPI + clarithromycin + amoxicillin where resistance is < 15%. Confirm eradication with breath test or stool antigen 4+ weeks post-treatment.
When is endoscopy needed?
Indications: active GI bleeding (hematemesis, melena), persistent symptoms despite PPI, alarm features (weight loss, dysphagia, age > 60 with new symptoms, anemia, vomiting). Endoscopy allows visualization, biopsy (diagnose H. pylori, exclude malignancy in gastric ulcers), and therapeutic intervention — clipping, injection epinephrine, thermal coagulation for bleeding ulcers. All gastric ulcers need biopsy and follow-up endoscopy to confirm healing and rule out cancer.
What is Zollinger-Ellison syndrome?
Gastrinoma (gastrin-secreting tumor, usually in pancreas or duodenum) causing massive acid hypersecretion and refractory ulcers, often multiple and in unusual locations (jejunum). Present with severe ulcers, diarrhea (excess acid inactivates pancreatic enzymes), weight loss. Diagnosis: fasting gastrin > 1000 pg/mL with elevated gastric acid output, secretin stimulation test (paradoxical gastrin rise). Treatment: high-dose PPIs and tumor localization/resection. 25% associated with MEN1.
What causes stress ulcers in critically ill patients?
Mucosal ischemia from hypotension, sepsis, or shock impairs prostaglandin synthesis and mucosal defense. Risk factors: mechanical ventilation > 48 hours, coagulopathy, head injury (Cushing ulcer), burns (Curling ulcer), spinal cord injury. Manifestation: typically painless GI bleeding. Prophylaxis with PPI or H2 blocker reduces clinically significant bleeding from 5% to 1% in high-risk ICU patients. Stop prophylaxis when oral feeds resume to avoid PPI overuse.