What is the pathophysiology of peptic ulcers in a typical adult patient?

Pathophysiology of Peptic Ulcer Disease

Core Mechanism

Peptic ulceration fundamentally occurs when acid-peptic damage to the gastroduodenal mucosa results in mucosal erosion that exposes underlying tissues to the digestive action of gastroduodenal secretions, representing an imbalance between aggressive factors (acid and pepsin) and mucosal defense mechanisms. 1

Primary Pathogenic Factors

Aggressive Factors

• Acid and pepsin secretion remains the critical permissive factor—the principle "no acid, no ulcer" holds true, as peptic ulceration cannot occur without gastric acid 2, 3
• Duodenal ulcer patients demonstrate increased acid-pepsin secretion in response to various stimuli, though this abnormality is not present in all patients and tends to cluster in subgroups 2
• Pepsin 1 (the ulcer-associated pepsin) has particularly potent proteolytic activity against the mucosal barrier 4

Defective Mucosal Defense

• Impaired defense mechanisms are relatively more important than aggressive factors in the pathogenesis, particularly for acute ulcers and gastric corpus ulcers 2, 3
• Key defense defects include:
  • Reduced prostaglandin synthesis and release 3
  • Impaired mucus and bicarbonate secretion 3
  • Compromised luminal hydrophobic layer 3
  • Possible defects in gastric mucosal blood flow 2

Major Etiologic Agents

Helicobacter pylori Infection

• H. pylori is the main causative agent in gastroduodenal ulcer disease, representing the predominant mechanism worldwide and fundamentally changing the epidemiology of peptic ulcer disease 5, 6
• The infection is found in approximately 53% of patients with bleeding ulcers, surpassing NSAIDs as the most commonly identified risk factor 5
• H. pylori increases the risk of upper GI complications in NSAID users by 2- to 4-fold 5

NSAID and Aspirin Use

• NSAIDs are the second most important pharmacologic cause, affecting acid secretion in the gastric mucosa 5, 6
• The gastric mucosa is at least as vulnerable as the duodenal mucosa to NSAID injury, and probably more so—most drug-induced ulcers occur in the stomach 2
• When aspirin is combined with NSAIDs, the relative risk of GI bleeding increases to more than 10 times that seen with either agent alone 5
• The combination of H. pylori infection and NSAID use synergistically increases the risk of bleeding ulcers more than sixfold 7

Additional Contributing Factors

• Corticosteroids affect acid secretion and increase risk, particularly when combined with NSAIDs 5, 6
• Smoking and high-salt-content diet alter gastric mucosal integrity 5, 6
• Alcohol abuse has contributed to changing disease epidemiology 1

Pathophysiologic Distinctions by Ulcer Type

Acute Ulcers and Erosions

• Present clinically with gastrointestinal bleeding or perforation rather than pain 2
• Local ischemia is the earliest recognizable gross lesion 2
• Factors concerning mucosal defense are relatively more important than aggressive factors 2
• If they heal, there is no predictable recurrence pattern 2

Chronic Duodenal Ulcers

• Characterized by recurrent true peptic ulcers (penetrating the muscularis mucosae) that usually present with abdominal pain 2
• Approximately 50% of patients experience recurrence within one year if anti-ulcer medication is stopped 2
• Recent evidence indicates genetic and familial factors play a role 2
• Patients demonstrate postprandial hypersecretion of acid and hypergastrinemia with accelerated gastric emptying in "idiopathic" cases 8

Chronic Gastric Ulcers

• In gastric ulcers of the corpus, defective defense mechanisms appear more important than aggressive factors 2
• Key mechanisms include:
  • Duodenogastric reflux 2
  • Atrophic gastritis 2
• Nevertheless, antisecretory medications still accelerate healing, indicating acid remains permissive 2

Critical Clinical Implications

• Heterogeneity is the most important consideration in peptic ulcer pathophysiology—different causes often coexist in a given patient 2, 8
• As many as 20% of ulcer patients may be H. pylori-negative upon presentation, with other causes including surreptitious NSAID use, hypersecretory states, or Crohn's disease 8
• The principle "normal healing, no ulcer" is as valid as "no acid, no ulcer," emphasizing that correction of mucosal defense deficiencies is critical 3