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 Overview of Gastritis Gastritis is inflammation of the gastric mucosa caused by any of several conditions, including infection (Helicobacter pylori), drugs (nonsteroidal anti-inflammatory drugs, alcohol),... read more , 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 Prostaglandins Drugs for decreasing acidity are used for peptic ulcer, gastroesophageal reflux disease (GERD), and many forms of gastritis. Some drugs are used in regimens for treating Helicobacter pylori... read more 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 Helicobacter pylori Infection Helicobacter pylori is a common gastric pathogen that causes gastritis, peptic ulcer disease, gastric adenocarcinoma, and low-grade gastric lymphoma. Infection may be asymptomatic or... read more ) predispose to gastritis and peptic ulcer disease Peptic Ulcer Disease A peptic ulcer is an erosion in a segment of the gastrointestinal mucosa, typically in the stomach (gastric ulcer) or the first few centimeters of the duodenum (duodenal ulcer), that penetrates... read more .
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.