Peptic Ulcer Disease II: Pathophysiology

The gastric and duodenal mucosa contain a superficial gel layer that functions as a protective barrier against hydrochloric acid and pepsin. This barrier prevents penetration of aggressive gastric juices and protects epithelial cells from injury. When the mucosal barrier is compromised, it secretes less mucus, reducing resistance to aggressive factors and leading to inflammation and mucosal erosion.

NSAIDs compromise mucosal defenses by hindering prostaglandin production. Prostaglandins are crucial for maintaining the gastric mucosal barrier through mucus and bicarbonate secretion, regulating blood flow, curbing gastric acid production, and fostering cell repair. Without adequate prostaglandins, the protective mechanisms weaken, allowing acid and pepsin to damage the mucosa.

Aggressive factors including NSAIDs, alcohol, Helicobacter pylori, and gastric juices compromise mucosal defense and allow back diffusion of hydrogen ions, injuring epithelial cells. These factors increase the concentration or activity of acid-pepsin or decrease the resistance of the protective mucosal barrier, disrupting the normal balance that typically exists between gastric juice secretion and mucosal defenses.

Mucosal defensive mechanisms include tight intercellular junctions, mucus generation, bicarbonate secretion, prostaglandins, adequate mucosal blood flow, cellular restitution, and epithelial renewal. These mechanisms work together to maintain the integrity of the protective barrier. Disruptions in any of these mechanisms may increase acid-pepsin activity or decrease mucosal barrier resistance, leading to ulcer development.

Helicobacter pylori erodes the protective mucous layer of the gastric and duodenal mucosa, causing mucosal damage and inflammation. This bacterial infection compromises the mucosal defense mechanisms, allowing hydrogen ions to infiltrate and harm epithelial cells. The resulting inflammation and erosion of the mucosa lead to peptic ulcer formation.

Adequate mucosal blood flow is required to keep the mucosa healthy by supplying nutrients and eliminating toxins. Reduced blood flow can cause mucosal damage and lead to ulcers. Blood flow is one of several mucosal defensive mechanisms that work together to maintain barrier integrity and support cellular restitution and epithelial renewal.

Bicarbonate from stomach and duodenal cells normally neutralizes gastric acid, shielding the mucosa from damage. When bicarbonate secretion is impaired, the mucosa loses this critical protective mechanism. This allows gastric acid and pepsin to damage the epithelial cells more readily, contributing to inflammation, injury, and erosion that characterize peptic ulcer disease and clinical manifestations and diagnostic studies.