The gastric glands contain parietal cells that secrete hydrochloric acid (HCl) for digestion. The cells secrete HCl because it is highly corrosive and essential for breaking down food. To achieve this, they secrete hydrogen and chloride ions into the lumen of the gastric glands, which combine to form HCl.

Within parietal cells, carbonic acid is first formed through the reaction of water and carbon dioxide. The dissociation of carbonic acid releases bicarbonate and hydrogen ions. The bicarbonate ions are exchanged for chloride ions from the interstitial fluid. When gastric glands are actively secreting, enough bicarbonate ions diffuse into the bloodstream from the interstitial fluid to increase the pH of the blood. This sudden influx of bicarbonate ions is called the alkaline tide. The chloride ions diffuse across the parietal cell and into the lumen of the gastric gland, while the proton pumps actively transport the hydrogen ions. These ions create an acidic environment that is necessary for digestion and pathogen elimination, but they can also harm the stomach lining.

To protect itself from this highly acidic environment, the stomach lining creates barriers. These include a thick mucus layer rich in bicarbonate ions, which acts as a physical barrier. Tight junctions between epithelial cells further strengthen the integrity of the mucosal barrier by preventing acid leakage into the underlying tissues. The mucosal epithelium is continuously replenished by the division of underlying stem cells, facilitating its high rate of cell renewal and the maintenance of the barrier.

Despite the robust nature of the mucosal barrier, certain factors can compromise its integrity, leading to gastric ulcers. Common causes include infections caused by Helicobacter pylori, nonsteroidal anti-inflammatory drugs (NSAIDs) use, and an imbalance between acid production and mucus secretion. These conditions can cause inflammation and damage to the epithelial cells, ultimately forming ulcers.