What is Acid Peptic Disease?
Acid peptic disease encompasses a group of conditions characterized by mucosal ulceration in the stomach and/or proximal duodenum, resulting from an imbalance between aggressive acid-pepsin secretion and protective mucosal defense mechanisms. 1, 2
Core Pathophysiology
Acid peptic disease develops when tissue loss breaches the muscularis mucosae in the acid-peptic environment of the gastroduodenum. 2 The fundamental principle remains that ulcers never develop spontaneously in healthy gastroduodenal mucosa—they represent the ultimate consequence of disequilibrium between injurious and protective factors. 2
Aggressive Factors
- Strong gastric acid and high proteolytic pepsin activity constitute the dominant aggressors, supporting Schwartz's dictum "no acid, no ulcer." 2
- Acid and pepsin appear necessary but not sufficient ingredients in the ulcerative process, as the majority of gastric ulcers and substantial numbers of duodenal ulcers occur without increased acid secretion. 3
Defensive Mechanisms
The protective barrier consists of multiple layers: 2
- Phospholipid surfactant layer covering the mucus bicarbonate gel
- Mucus bicarbonate layer overlying the epithelium
- Tight junctional structures between epithelial cells that restrict proton permeability
- Epithelial trefoil peptides contributing to healing after injury
Primary Etiologies
Helicobacter pylori Infection
H. pylori infection is the leading cause of peptic ulcer disease, present in 85-100% of duodenal ulcers and 70-90% of gastric ulcers. 1, 2 In the absence of NSAIDs and gastrinoma, most gastric ulcers and all duodenal ulcers occur with H. pylori infection. 3 Evidence increasingly supports H. pylori as a necessary ingredient in ulceration, similar to acid and pepsin. 3
NSAID-Induced Injury
Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) represent the second major cause, likely through inhibition of prostaglandin production with loss of protective effects. 2, 3 NSAIDs cause significant numbers of both gastric and duodenal ulcers. 3
Other Mechanisms
Additional injurious mechanisms include: 2
- Physicochemical and caustic injury
- Vascular disorders interfering with mucosal perfusion
- Drug-induced injury beyond NSAIDs
Clinical Spectrum
Included Conditions
Acid peptic disorders encompass: 1
- Gastric ulcers
- Duodenal ulcers
- Gastroesophageal reflux disease (GERD)
Epidemiology
Peptic ulcer disease occurs in 5-10% of people worldwide, though rates have decreased by more than half during the past 20 years due to H. pylori management, conservative NSAID use, and widespread proton pump inhibitor availability. 4
Pathophysiologic Distinctions
Duodenal Ulcer Pattern
Duodenal ulcer typically involves: 3
- H. pylori infection and duodenitis
- Impaired duodenal bicarbonate secretion
- Moderate increases in acid and peptic activity
- Gastric metaplasia in the duodenum that becomes colonized by H. pylori
- Inflammation disrupting mucosal defense and regeneration
Gastric Ulcer Pattern
Gastric ulcer often occurs with: 3
- Decreased acid-peptic activity, suggesting mucosal defensive impairments are more important
- Combination of inflammation, protective deficiencies, and moderate acid-pepsin levels sufficient to induce ulceration
Treatment Principles
Acid Suppression Evolution
The therapeutic sequence has progressed from large-dose antacids to H2-receptor antagonists to proton pump inhibitors (PPIs), with longer intragastric pH >3 correlating with faster ulcer healing. 2 PPIs are more potent inhibitors of acid secretion than H2-receptor antagonists and demonstrate superior effectiveness in treating acid peptic disorders. 1
H. pylori Eradication
Current management includes combination antisecretory and antibiotic therapy for acute treatment of H. pylori-associated disease, as eradicating this organism results in considerable decrease in ulcer recurrence. 1 Standard triple eradication therapy is losing favor to quadruple therapy (PPI, bismuth, tetracycline, metronidazole). 2
NSAID Management
When NSAIDs cannot be discontinued, antisecretory cotherapy should be considered, though PPIs reduce but do not eliminate the risk of NSAID-induced ulcers, reflecting untargeted pathophysiologic pathways. 5
Important Clinical Caveat
Patient self-medication with over-the-counter H2-receptor antagonists may impact the potential for reducing peptic ulcer recurrence in patients with H. pylori infection—patients with recurrent disease require aggressive education at point-of-sale to seek medical treatment. 1