Pathophysiology of Peptic Ulcer Disease: Injurious Factors

The vagus nerve releases acetylcholine and GRP, which stimulate acid secretion through multiple pathways. Acetylcholine binds to muscarinic receptors on parietal and enterochromaffin-like cells, activating calcium-dependent and cAMP-dependent signaling cascades. GRP stimulates antral G cells to secrete gastrin, further promoting acid production through gastrin-cholecystokinin receptors.

Histamine is released by enterochromaffin-like cells and binds to H2 receptors on parietal cells. This binding initiates the cyclic AMP pathway, which activates protein kinase A and stimulates the proton pump to produce hydrochloric acid. Histamine acts as a key mediator linking neural and hormonal signals to acid secretion.

Gastrin and acetylcholine activate two pathways in parietal cells. The calcium-dependent pathway involves Gq proteins and phospholipase C, releasing calcium from the endoplasmic reticulum to activate protein kinases. The cAMP-dependent pathway involves Gs protein and adenylyl cyclase, converting ATP to cAMP and activating protein kinase A, both ultimately stimulating the proton pump.

H. pylori infection decreases the number of antral D cells, reducing somatostatin production. Somatostatin normally inhibits gastrin secretion, so its loss leads to increased gastrin levels and excessive acid production. This overproduction of gastric acid erodes the protective mucosal lining, contributing to ulceration and requiring treating helicobacter pylori in peptic ulcers antimicrobial therapy.

Somatostatin is produced by antral D cells and acts as an inhibitory hormone on gastrin secretion. In a healthy stomach, somatostatin maintains the balance between acid production and mucosal defense. When D cell populations are reduced by H. pylori infection, somatostatin levels drop, removing this inhibitory control and allowing excessive gastrin-stimulated acid production.

Both NSAIDs and H. pylori infection disrupt the balance between gastric acid and pepsin secretion and mucosal defense mechanisms. H. pylori reduces somatostatin-producing D cells, increasing acid production. NSAIDs directly damage the protective mucosal lining. Together or separately, these factors erode the mucosal barrier and contribute to ulceration.

The mucosal epithelium contains parietal cells that produce gastric acid, chief cells that secrete pepsinogen, and G cells in the antrum that secrete gastrin. In the fundic glands, enterochromaffin-like cells release histamine. Together, these cells coordinate acid and enzyme secretion through neural and hormonal signaling to support digestion.