Chronic Peptic Ulcer

1. Epidemiology

• Affects more than 4 million individuals per year in the United States alone.
• Lifetime risk: ~10% in males, ~4% in females.
• Incidence of H. pylori-related ulcers is falling as infection rates decline, but NSAID-related ulcers (especially in those over 60) are rising.
• Duodenal ulcers are more common than gastric ulcers; both share largely indistinguishable symptoms.

2. Etiology and Risk Factors

Key Causes

Associated Conditions

• Alcohol-related cirrhosis
• Chronic obstructive pulmonary disease
• Chronic renal failure and hyperparathyroidism (hypercalcemia stimulates gastrin → acid)

More than 70% of PUD cases are associated with H. pylori infection. However, only 5-10% of infected individuals develop ulcers, so host factors and bacterial strain variation both matter.

3. Pathogenesis in Detail

1. Mucus-bicarbonate layer secreted by surface epithelium and Brunner's glands
2. Mucosal blood flow (delivering oxygen and removing acid)
3. Epithelial tight junctions
4. Prostaglandins (E2 and I2)
5. Pancreatic bicarbonate neutralizing duodenal acid

• H. pylori in the antrum → antral gastritis → loss of somatostatin-secreting D cells → unchecked gastrin → parietal cell hyperplasia → excess HCl
• H. pylori also directly damages the duodenal mucosa and reduces bicarbonate secretion
• NSAIDs deplete prostaglandins systemically (COX-1 inhibition) even if taken parenterally or rectally
• Both H. pylori and NSAIDs act synergistically, especially with low-dose aspirin in cardiovascular patients

4. Morphology (Gross and Histological)

Gross Appearance

• Solitary in >80% of patients
• Round to oval, sharply punched-out ("cookie cutter") defect
• Mucosal margin is flat or at the same level as surrounding mucosa (heaped/rolled margins suggest malignancy)
• Located most often in the proximal duodenum (within a few cm of the pyloric valve) or lesser curvature of gastric antrum/body junction
• The base is smooth and clean due to peptic digestion of exudate

Histological Appearance

1. Superficial fibrinoid necrosis - thin layer of fibrinoid debris
2. Neutrophilic infiltrate - active inflammation
3. Granulation tissue - immature vessels, neutrophils, mononuclear cells
4. Fibrous/collagenous scar - the defining feature of "chronic" ulcer; extends through the full thickness of the wall

• Larger vessels in the scarred base are thickened and may be thrombosed - rupture of these causes life-threatening hemorrhage
• Scarring may contract the surrounding mucosa into radiating folds
• Foveolar (gastric-type) metaplasia in the duodenum is common and may be a protective adaptation
• In duodenal chronic peptic disease, the ulcer penetrates the muscular coat, leading to fibrosis and possible deformity (e.g., pyloric stenosis from scarring)

5. Sites of Occurrence

6. Clinical Features

Symptoms

• Epigastric pain - gnawing or burning quality, classically 1-3 hours after meals, worse at night (11 pm - 2 am)
• Food/alkali relieves the pain (esp. duodenal ulcers)
• Periodicity - symptoms may disappear for weeks/months and recur (related to spontaneous healing and re-ulceration)
• Nausea, vomiting, bloating, belching
• Weight loss (or rarely weight gain)
• Referred pain to the back, left upper quadrant, or chest (penetrating ulcers)
• Iron deficiency anemia from chronic slow bleeding

Examination

• Epigastric tenderness on palpation
• Gastric outlet obstruction: succussion splash, visible peristalsis, distension
• Acute complications produce peritonism (perforation) or hemodynamic instability (major bleed)

7. Complications

8. Investigations

• Upper GI endoscopy (OGD): investigation of choice; allows direct visualization + biopsy
  • All gastric ulcers require multiple biopsies to exclude malignancy
  • CLO (Campylobacter-like organism) test on antral biopsy for H. pylori
• Barium meal: shows ulcer crater (filling defect with radiating folds); largely replaced by endoscopy
• H. pylori testing: urea breath test, stool antigen test, serology, or histology
• Fasting serum gastrin: if Zollinger-Ellison syndrome suspected
• FBC: for iron deficiency anemia
• Erect CXR: free air under diaphragm in perforation

9. Treatment

Medical (First-Line)

• Standard: PPI + Amoxicillin + Clarithromycin for 7-14 days
• Quadruple therapy (PPI + bismuth + metronidazole + tetracycline) for clarithromycin-resistant strains
• Successful eradication reduces recurrence to <20% (vs. ~80% without eradication)
• Confirm eradication with urea breath test (at least 4 weeks after therapy, 2 weeks off PPI)

• Proton pump inhibitors (PPIs): block H⁺/K⁺-ATPase; mainstay of acid suppression; render patient virtually achlorhydric
• H2-receptor antagonists (e.g., ranitidine): block histamine effect on parietal cells; reduce acid by 70-80%; now largely superseded by PPIs
• Potassium-competitive acid blockers (P-CABs) (e.g., vonoprazan): bind to the K⁺-binding region of the proton pump; faster and more consistent acid suppression

• Stop NSAIDs, COX-2 inhibitors, corticosteroids where possible
• Add PPI for patients who must continue NSAIDs
• Cessation of smoking and alcohol

Endoscopic Management (for Bleeding Ulcers)

• Injection therapy (adrenaline), thermal coagulation, hemoclips
• Rockall score used to stratify risk (see scoring table from Sleisenger & Fordtran)

Surgical Management (Now Rare Electively)

• No longer routine for uncomplicated PUD
• Reserved for emergencies: bleeding that fails endoscopy, perforation, obstruction
• Perforation: omental patch repair (Graham's patch) ± lavage; laparoscopic approach now preferred
• Gastrectomy (Billroth I or II): historical elective operations; now only for emergency or failed endoscopy
• Vagotomy (highly selective or truncal + drainage): reduces acid secretion; largely historical

10. Special Situations

Summary

Chronic peptic ulcer = a full-thickness mucosal defect (through mucosa into muscularis, with a fibrous scar base) caused by acid-peptic digestion exceeding the mucosal defenses. The two dominant causes are H. pylori infection and NSAID use. The ulcer is almost always solitary, round, with a punched-out clean base, and most commonly sited in the duodenal bulb or gastric lesser curvature. Medical management with PPI + H. pylori eradication is the cornerstone of treatment; surgery is reserved for complications.