Hydrochloric acid secretion Hydrochloric acid is formed in the following manner: • Hydrogen ions are formed from the dissociation of
carbonic acid. Water is a very minor source of hydrogen ions in comparison to carbonic acid. Carbonic acid is formed from
carbon dioxide and water by
carbonic anhydrase. • The bicarbonate ion (HCO3−) is exchanged for a chloride ion (Cl−) on the basal side of the cell and the bicarbonate diffuses into the venous blood, leading to an
alkaline tide phenomenon. •
Potassium (K+) and chloride (Cl−) ions diffuse into the
canaliculi. • Hydrogen ions are pumped out of the cell into the canaliculi in exchange for potassium ions, via the
H+/K+-ATPase. These pumps are increased in number on luminal side by fusion of tubulovesicles during activation of parietal cells and removed during deactivation. This pump maintains a million-fold difference in proton concentration. ATP is provided by the numerous mitochondria. As a result of the cellular export of hydrogen ions, the gastric lumen is maintained as a highly acidic environment. The acidity aids in digestion of food by promoting the unfolding (or
denaturing) of ingested
proteins. As proteins unfold, the
peptide bonds linking component
amino acids are exposed. Gastric HCl simultaneously cleaves
pepsinogen, a
zymogen, into active
pepsin, an endopeptidase that advances the digestive process by breaking the now-exposed peptide bonds, a process known as
proteolysis.
Regulation Parietal cells
secrete acid in response to three types of
stimuli: •
Histamine, stimulating
H2 histamine receptors (most significant contribution). •
Acetylcholine (ACh), from
parasympathetic activity via the
vagus nerve and enteric nervous system, stimulating
M3 receptors. •
Gastrin, stimulating
CCK2 receptors (least significant contribution, but also causes histamine secretion by local
ECL cells). Activation of histamine through H2 receptor causes increases in the intracellular
cAMP level, while ACh through M3 receptor and gastrin through CCK2 receptor increases intracellular calcium level. These receptors are present on basolateral side of membrane. Increased cAMP level results in increased protein kinase A. Protein kinase A phosphorylates proteins involved in the transport of
H+/K+-ATPase from the cytoplasm to the
cell membrane. This causes resorption of K+ ions and secretion of H+ ions. The
pH of the secreted fluid can fall by 0.8. Gastrin primarily induces acid-secretion indirectly, increasing histamine synthesis in
ECL cells, which in turn signal parietal cells via histamine release and H2 stimulation. Gastrin itself has no effect on the maximum histamine-stimulated gastric acid secretion. The effect of histamine, acetylcholine and gastrin is synergistic, that is, effect of two simultaneously is more than additive of effect of the two individually. It helps in non-linear increase of secretion with stimuli physiologically.
Intrinsic factor secretion Parietal cells also produce a
glycoprotein known as
intrinsic factor. Intrinsic factor is required for the absorption of
vitamin B in the diet. A long-term
deficiency in vitamin B12 can lead to
megaloblastic anemia, characterized by large fragile
red blood cells.
Pernicious anaemia results from autoimmune destruction of gastric parietal cells, precluding the synthesis of intrinsic factor and, by extension, absorption of vitamin B12. Pernicious anemia also leads to megaloblastic anemia.
Atrophic gastritis, particularly in the elderly, will cause an inability to absorb B12 and can lead to deficiencies such as decreased DNA synthesis and
nucleotide metabolism in the bone marrow. ==Clinical significance==