Acid is secreted by parietal cells in the proximal two thirds (body) of the stomach. Gastric acid aids digestion by creating the optimal pH for pepsin and gastric lipase and by stimulating pancreatic bicarbonate secretion. Acid secretion is initiated by food: the thought, smell, or taste of food effects vagal stimulation of the gastrin-secreting G cells located in the distal one third (antrum) of the stomach. The arrival of protein to the stomach further stimulates gastrin output. Circulating gastrin triggers the release of histamine from enterochromaffin-like cells in the body of the stomach. Histamine stimulates the parietal cells via their H2 receptors. The parietal cells secrete acid, and the resulting drop in pH causes the antral D cells to release somatostatin, which inhibits gastrin release (negative feedback control).
Acid secretion is present at birth and reaches adult levels (on a weight basis) by age 2. There is a decline in acid output in older patients who develop chronic gastritis, but acid output is otherwise maintained throughout life.
Normally, the gastrointestinal mucosa is protected by several distinct mechanisms:
Mucosal production of mucus and HCO3 creates a pH gradient from the gastric lumen (low pH) to the mucosa (neutral pH). The mucus serves as a barrier to the diffusion of acid and pepsin.
Epithelial cells remove excess hydrogen ions (H+) via membrane transport systems and have tight junctions, which prevent back diffusion of H+ ions.
Mucosal blood flow removes excess acid that has diffused across the epithelial layer.
Several growth factors (eg, epidermal growth factor, insulin-like growth factor I) and prostaglandins have been linked to mucosal repair and maintenance of mucosal integrity.
Factors that interfere with these mucosal defenses (particularly nonsteroidal anti-inflammatory drugs [NSAIDs] and Helicobacter pylori infection) predispose to gastritis and peptic ulcer disease.
NSAIDs promote mucosal inflammation and ulcer formation (sometimes with gastrointestinal bleeding) both topically and systemically. By inhibiting prostaglandin production via blockage of the enzyme cyclooxygenase (COX), NSAIDs reduce gastric blood flow, reduce mucus and HCO3 secretion, and decrease cell repair and replication. Also, because NSAIDs are weak acids and are nonionized at gastric pH, they diffuse freely across the mucus barrier into gastric epithelial cells, where H+ ions are liberated, leading to cellular damage. Because gastric prostaglandin production involves the COX-1 isoform, NSAIDs that are selective COX-2 inhibitors have fewer adverse gastric effects than other NSAIDs.
