A canaliculus is an adaptation found on gastric parietal cells. It is a deep infolding, or little channel, which serves to increase the surface area, e.g. for secretion. The parietal cell membrane is dynamic; the numbers of [|canaliculi] rise and fall according to secretory need. This is accomplished by the fusion of canalicular precursors, or "tubulovesicles", with the membrane to increase surface area, and the reciprocal endocytosis of the canaliculi to decrease it. 00
Function
Hydrochloric acid secretion
Hydrochloric acid is formed in the following manner:
Potassium and chloride 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 receptors are increased in number on lumenal side by fusion of tubulovesicles during activation of parietal cells and removed during deactivation. This receptor 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 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:
Activation of histamine through H2 receptor causes increases 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/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 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 erythrocytes. 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
Peptic ulcers can result from over-acidity in the stomach. Antacids can be used to enhance the natural tolerance of the gastric lining. Antimuscarinic drugs such as pirenzepine or H2 antihistamines can reduce acid secretion. Proton pump inhibitors are more potent at reducing gastric acid production since that is the final common pathway of all stimulation of acid production.
In pernicious anemia, autoantibodies directed against parietal cells or intrinsic factor cause a reduction in vitamin B12 absorption. It can be treated with injections of replacement vitamin B12.
Achlorhydria is another autoimmune disease of the parietal cells. The damaged parietal cells are unable to produce the required amount of gastric acid. This leads to an increase in gastric pH, impaired digestion of food and increased risk of gastroenteritis.
