Peptic ulcer disease

The two major etiologic factors responsible for peptic ulceration are infection by the gram-negative gastric pathogen Helicobacter pylori and the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). There is some synergy between these two major causes.[13]

Rarer causes include gastric ischemia (responsible for the "stress ulcers" that can occur in patients with multiple organ failure in intensive care units), Zollinger-Ellison syndrome (a syndrome of gastric acid hypersecretion caused by a gastrin-secreting neuroendocrine tumor), certain drugs (e.g., potassium chloride, bisphosphonates), infections (cytomegalovirus in patients with HIV, and occasionally herpes simplex virus), and Crohn disease.[14] A small but increasing proportion of peptic ulcers seem truly idiopathic.[15][16]

Psychological stress may play a role in some patients. A population-based prospective study in Denmark that included 3379 individuals demonstrated that psychological stress increased the incidence of peptic ulcer in part by influencing health risk behaviors.[17] A higher incidence of ulcer disease is also reported after acute traumatic events such as bombing raids during World War II and following the Japanese tsunami.[18]

Peptic ulcers result from an imbalance between factors that can damage the gastroduodenal mucosal lining and defense mechanisms that normally limit the injury. Aggressive factors include gastric juice (including hydrochloric acid, pepsin, and bile salts refluxed from the duodenum), H pylori, and NSAIDs.[19] Mucosal defenses comprise a mucus bicarbonate layer secreted by surface mucus cells forming a viscous gel over the gastric mucosa. Also key is the integrity of tight junctions between adjacent epithelial cells, and the process of restitution, whereby any break in the epithelial lining is rapidly filled by adjacent epithelial and mucosal stromal cells that migrate to fill the gap. Mucosal defenses rely heavily on an adequate blood supply.

In general, duodenal ulcers are the result of hypersecretion of gastric acid related to H pylori infection (the majority of patients), whereas secretion is normal or low in patients with gastric ulcers.[19]

In duodenal ulcers, chronic H pylori infection confined mainly to the gastric antrum leads to impaired secretion of somatostatin and consequently increased gastrin release, resulting in gastric acid hypersecretion. In Zollinger-Ellison syndrome, a gastrin-secreting neuroendocrine tumor is the stimulus for high rates of gastric acid secretion.

In gastric ulcers, long-standing H pylori infection throughout the stomach accompanied by severe inflammation results in gastric mucin degradation, disruption of tight junctions between gastric epithelial cells, and the induction of gastric epithelial cell death. NSAIDs cause injury directly (involving trapping hydrogen ions) and indirectly (a systemic effect involving the inhibition of cyclo-oxygenases, especially COX-1) and increase bleeding risk through antiplatelet actions.[13][20]

General

Peptic ulcers are generally categorized as gastric or duodenal.

Pathophysiology

Classification

General