Epidemiology

Etiology

Common causes of PUD

The two major contributing factors to the development of PUD are gastrointestinal infection with H. pylori and nonsteroidal anti-inflammatory drug (NSAID) use.

• Helicobacter pylori infection
  • Associated with 40–70% of duodenal ulcers and 25–50% of gastric ulcers
• Chronic NSAID use

Associated risk factors

• Shared risk factors for PUD, GERD and gastritis (i.e., smoking, heavy alcohol use, glucocorticoids, caffeine)

Rare causes of PUD

• Acid hypersecretory states
  • Zollinger-Ellison syndrome

Pathophysiology

• H. pylori
  • Gastric ulcers
    • H. pylori colonizes the gastric body (corpus)
    • H. pylori secretes urease → conversion of urea to NH3 → alkalinization of acidic environment → survival of bacteria in gastric lumen
    • Bacterial colonization and attachment to epithelial cells → release of cytotoxins (e.g., cagA toxin) → disruption of the mucosal barrier and damage to underlying cells
  • Duodenal ulcers
    • H. pylori colonizes the gastric antrum, see Stomach histology
    • H. pylori inhibits somatostatin secretion → ↑ gastrin secretion → ↑ H⁺ secretion → excess H⁺ delivery to the duodenum
    • Direct spread of H. pylori to the duodenum → inhibition of duodenal HCO₃^- secretion→ acidification and insufficient neutralization of duodenal contents

Clinical features

Diagnostics

Initial tests

• Noninvasive: Order one of the following if EGD is not indicated.
  • Urea breath test: The labeled carbon isotope in a breath sample is quantified.
  • H. pylori stool antigen test: detects H. pylori antigens via an enzyme immunoassay
• Invasive: Order one or both of the following tests (performed on a gastric biopsy sample) for patients with indications for EGD.
  • Histology (gold standard)
    • Staining and direct microscopic identification
    • Typical microscopic appearance of H. pylori: curved, gram-negative rods with multiple flagella
    • Sensitivity and specificity are not affected by recent PPI treatment.
  • Rapid urease test: detects the amount of ammonia produced by H. pylori during urea hydrolysis
    • The rapid urease test is an indirect test for H pylori based on bacterial production of the enzyme urease, which splits gastric urea into ammonia and CO2. During the test, biopsy specimens are exposed to a solution containing urea and a pH indicator such as phenol red, which changes color from yellow to pink at alkaline pH. A color change indicates the presence of bacterial urease and confirms active H pylori infection.

Indications for biopsy

• Gastric ulcers
  • Biopsies are recommended in most cases.
  • Multiple biopsies are recommended.
  • From the edge and base of the ulcer (essential to rule out malignancy, which is not uncommon in gastric ulcers)
    • The central part of the ulcer may contain necrotic tissue, fibrin slough, and other debris, which are typically not useful for diagnostic purposes.
  • Multiple biopsies from different areas of the stomach lining, including those not surrounding the ulcer (to test for H. pylori)
• Duodenal ulcers
  • Obtain biopsies from ulcers with endoscopic features that suggest malignancy.
  • Duodenal ulcers are usually benign and do not require routine biopsy.

Treatment

Complications

Bleeding peptic ulcer

• Etiology
  • Posterior duodenal ulcers are more likely to bleed than anterior duodenal ulcers.
  • Gastric ulcers of the lesser curvature may cause bleeding from the left gastric artery.
  • Duodenal ulcers of the posterior wall may cause bleeding from the gastroduodenal artery.

Peptic ulcer perforation

• Definition: full-thickness injury and loss of bowel wall integrity that results in leakage of gastrointestinal contents
  • The second most common complication of PUD
  • PUD is the most common cause of GI perforation.
• Etiology
  • Prepyloric gastric ulcers are the most common cause of perforation.
  • Duodenal ulcers of the anterior wall are more likely to perforate than ulcers of the posterior wall.
    • This is because less protection is provided by the surrounding anatomical structures.
• Clinical features
  • Sudden, diffuse abdominal pain and rigidity
  • Fever, tachycardia, tachypnea, hypotension
  • Pneumoperitoneum
  • Shoulder pain (irritation of the phrenic nerve)