Current pathophysiology of peptic ulcer disease: balance, aggression and defense

Peptic ulcer disease has traditionally been explained through an acid-centered model focused on gastric hypersecretion. However, accumulating scientific evidence over recent decades has demonstrated that acid, while necessary, is not sufficient by itself to account for mucosal injury. The current pathophysiological concept recognizes peptic ulcer disease as the result of a dynamic imbalance between aggressive factors and gastroduodenal mucosal defense mechanisms. Major aggressive factors include hydrochloric acid, pepsin, Helicobacter pylori, and nonsteroidal anti-inflammatory drugs, whereas mucosal defense relies on the mucus-bicarbonate layer, prostaglandins, mucosal blood flow, epithelial integrity, and local immune responses. The interaction among these elements is further modulated by inflammatory pathways, genetic and epigenetic factors, and host susceptibility, explaining the marked clinical heterogeneity observed among patients. This article provides a comprehensive and up-to-date review of the pathophysiological mechanisms involved in peptic ulcer disease, emphasizing the balance between mucosal aggression and defense and its clinical relevance for understanding disease persistence, recurrence, and complications, based on contemporary scientific evidence.