Pathophysiology

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. Mucosal defenses comprise a mucus bicarbonate
layer secreted by surface mucus cells forming a viscous gel over the gastric
mucosa; 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 migrating and
flattening to fill the gap. Mucosal defenses depend on an adequate blood
supply and on formation within the gastric mucosa.
In general, duodenal ulcers are the result of hypersecretion of gastric
acid related to H pylori infection (the majority of cases), whereas secretion
is normal or low in patients with gastric ulcers.
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 tumour is the stimulus for high rates of gastric acid secretion.
In gastric ulcers, longstanding 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 anti-platelet actions. Chronic gastric
ischaemia underlies the stress ulcers of patients in intensive care.