Stomach Acid Secretion

Overview
  • Stomach acid is secreted by parietal cells located within oxyntic glands of the stomach. The primary purpose of stomach acid is to lower the pH of the gastric contents sufficiently to allow activation of pepsinogen to pepsin. Because the stomach is the only place in the alimentary tract with a low pH, this allows pepsin to be active only in the stomach whose mucosa possesses sufficient protection from the enzyme's activity.
Mechanism
  • Overview
    • Gastric Acid is ultimately derived by combining carbon dioxide and water to form carbonic acid. The hydrogen ion of carbonic acid is transported into the stomach lumen while the resultant bicarbonate ion is transported into the blood stream. This bicarbonate ion is later transported into the lumen of the duodenum where it is used to neutralize the previously generated gastric acid.
  • Molecular Mechanism
    • CO2 within parietal cells is transformed, by carbonic anhydrase, to H2CO3, which immediately splits into H+ and HCO3-. The generated H+ ion is actively transported into the lumen of the oxyntic gland using an HK ATPase on the cell's apical membrane. The generated HCO3- ion is passively transported into the blood in exchange for a chloride ion on the basolateral membrane.
Regulation
  • Overview:
    • Three stimuli directly induce stomach acid secretion by parietal cells.
    • Acetylcholine: Acetylcholine is released by parasympathetic fibers in vagus nerve efferents which synapse directly onto parietal cells
    • Histamine: Histamine is released by enterochromaffin-like cells (ECLs) which lie directly adjacent to parietal cells in the oxyntic gland
    • Gastrin: Gastrin is released by G Cells present in the pyloric glands of the stomach (See Gastrin page for regulation)
  • Coordination
    • The vagus nerve helps coordinate these three stimuli so that they act in concert. Vagus nerve efferents also synapse on G Cells and induce release of gastrin (These synapses use the non-traditional neurotransmitter GRP). Vagus nerve efferents also synapse onto enterochromaffin cells and induce release of histamine.
  • Potentiation
    • These three chemical stimuli converging on the parietal cells have syndergistic effects on stomach acid production. This means that substantially more stomach acid is secreted by parietal cells when stimulated by all three molecules simultaneously. Consequently, pharmacological inhibition of just one stimulus can dramatically reduce stomach acid secretion.
Phases of Secretion
  • Overview
    • Secretion of stomach acid can be divided into three phases which correspond to the different stages of food ingestion. Each phase tends to induce stomach acid secretion with slightly different regulatory mechanisms.
  • Cephalic Phase:
    • This phase is initiated by the sensory experience of seeing and eating food and contributes about 20% of total acid secretion. stomach acid secretion in this phase is mainly induced by central activation of the vagus nerve
  • Gastric Phase:
    • This phase is initiated by entry of food into the stomach and contributes about 70% of total acid secretion. During the gastric phase a vagal reflex initiated by distension of the stomach further increases vagus nerve stimulation. In addition, local production of food metabolites, especially proteins and amino acids, directly induce gastrin release from G Cells.
  • Intestinal Phase:
    • This phase is initiated by entry of food into the duodenum and contributes about 10% of total acid secretion. It is not fully clear how this phase is regulated but may be due to small amounts of gastrin secretion by the duodenal small intestine mucosa.
Inhibition of Secretion
  • Several stimuli act to prevent over-secretion of stomach acid which can be damaging both to the stomach as well as the duodenum (following gastric emptying). Many of the inhibitory stimuli originate in the early small intestine (i.e. duodenum and jejunum) and act to inhibit secretion of stomach acid. They include both neural mechanisms as well as hormonal factors which are initiated by the presence of nutrients and acid-mediated irritation of the duodenal and jejunal small intestine mucosa. Important hormonal mediators are Gastrin Inhibitory Peptide and somatostatin.