Peptic Ulcer Disease: Causes, Pathogenesis, Diagnosis, and Management

Peptic ulcer disease (PUD) refers to chronic, recurrent ulcers that affect the gastric and duodenal mucosa. Ulcerations may also occur in the lower esophagus, at gastrojejunal anastomosis sites, and within Meckel’s diverticulum. PUD results from an imbalance between aggressive factors (gastric acid, pepsin, and external insults) and mucosal defenses.

Epidemiology and Risk Factors

• Prevalence: Affects 5–10% of the population over a lifetime, with duodenal ulcers more common than gastric ulcers.
• Age and Gender: Duodenal ulcers peak in younger adults; gastric ulcers in older adults; slightly more common in males.
• Helicobacter pylori Infection: Present in >70% of duodenal and 50% of gastric ulcers.
• NSAID Use: Chronic nonsteroidal anti-inflammatory drug use (aspirin, ibuprofen) increases risk of ulceration and bleeding.
• Lifestyle and Diet: Smoking, alcohol, caffeine, and high-stress lifestyles may exacerbate mucosal injury.
• Genetic and Comorbid Conditions: Zollinger–Ellison syndrome, stress ulcers (critically ill patients).

Pathogenesis

1. Acid–Pepsin Injury
2. Parietal cells secrete hydrochloric acid under stimulation by:
   • Acetylcholine (vagal tone)
   • Gastrin (G cells in the antrum)
   • Histamine (mast cells)

3. Increased parietal cell mass and hypersecretory states drive mucosal damage.

4. Helicobacter pylori

5. Colonizes the antral mucosa, producing urease and cytotoxins that disrupt the mucosal barrier.

6. Induces chronic inflammation and increases gastrin release.

7. NSAID-Induced Injury

8. Inhibition of cyclooxygenase enzymes reduces protective prostaglandins (PGE₂, PGI₂).

9. Impairs mucus and bicarbonate secretion and decreases mucosal blood flow.

10. Psychophysiological Factors

11. Stress and emotional disturbances enhance vagal tone, increase acid secretion, and impair mucosal blood flow via sympathetic activation and hypothalamic–pituitary–adrenal axis (cortisol release).

12. Antral Retention and Gastrin Hypersecretion

13. Delayed gastric emptying or pyloric spasm leads to food stasis, stimulating G cells and excess acid production.

14. Dietary Insults

15. Spicy foods, alcohol, and rough foods can directly irritate and damage the mucosa, promoting ulcer formation.

Clinical Manifestations

• Epigastric Pain: Burning or gnawing pain, often relieved by eating (duodenal) or worsened by food (gastric).
• Dyspepsia: Fullness, bloating, early satiety.
• Nausea and Vomiting: Occasional, particularly with gastric outlet obstruction.
• Alarm Symptoms: Weight loss, anemia, hematemesis, melena, or obstruction.

Diagnosis

• Endoscopy:
• Direct visualization and biopsy to rule out malignancy.
• H. pylori Testing:
• Urea breath test, stool antigen, or biopsy-based tests.
• Laboratory Studies:
• CBC (anemia), serum gastrin levels if Zollinger–Ellison suspected.
• Imaging:
• Barium swallow for suspected perforation or obstruction when endoscopy is contraindicated.

Management

1. Eradication of H. pylori (if positive)

• Triple Therapy: PPI + clarithromycin + amoxicillin (or metronidazole) for 10–14 days.
• Quadruple Therapy: PPI + bismuth + tetracycline + metronidazole if resistance or prior treatment failure.

2. Acid Suppression

• Proton Pump Inhibitors (PPIs): Omeprazole, esomeprazole preferred for rapid ulcer healing.
• H2-Receptor Antagonists: Ranitidine or famotidine as adjuncts or for mild cases.

3. Mucosal Protectants

• Sucralfate: Binds to ulcer base and protects against acid.
• Prostaglandin Analogues: Misoprostol for NSAID-induced ulcers (caution in pregnancy).

4. Lifestyle and Supportive Measures

• Discontinue NSAIDs and other ulcerogenic medications if possible.
• Smoking cessation and moderation of alcohol and caffeine.
• Dietary modifications: small, frequent meals; avoid irritants.

5. Surgical Intervention (rare)

• Indicated for complications: bleeding, perforation, obstruction.
• Options include vagotomy and pyloroplasty or ulcer excision.

Prevention and Patient Education

• H. pylori Screening in high-prevalence areas or first-degree relatives of ulcer patients.
• NSAID Stewardship: Use COX-2 selective agents or co-therapy with PPIs when NSAID use is unavoidable.
• Stress Management: Psychosocial interventions to control stress-related acid secretion.
• Symptom Awareness: Prompt evaluation of alarm signs.

References

1. Malfertheiner P, et al. Management of Helicobacter pylori infection: the Maastricht V/Florence Consensus Report. Gut. 2022.
2. Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2020.
3. Sonnenberg A. Review article: Historical perspective of the epidemiology of peptic ulcer disease. Aliment Pharmacol Ther. 2018.
4. Vakil N, et al. The Montreal Definition and Classification of GERD. Am J Gastroenterol. 2006.