Gastric Physiology
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The stomach can be roughly divided into two regions, which contain two different lots of cells, with different functions

  • Oxyntic glandular area – this contains oxyntic (parietal cells) that secrete gastric juice and intrinsic factor, as well as chief (peptic cells) that secrete pepsinogen
  • Antral (lower) region – this contains G cells that secrete gastrin. G cells are also found in the duodenum.

There are also two other types of cell found all over the stomach:

  • ECL cells – which secrete histamine
  • D cells – which secrete somatostatin

Most functional cells of the stomach are found in gastric pits. The endocrine (G cells) tend to be closer to the bottom of the pit, as this is closer to blood vessels. At the top of the pits are the mucous secreting cells. This helps to protect cells in the pit from acid.

  • Note how mucous cells secrete an alkaline juice, as opposed to the acid secretion of oxyntic (parietal) cells.

The higher the rate of secretion of gastric juice, the more acidic it is. Remember it is hydrochloric acid (H+ and Cl-) that is secreted by the oxyntic cells.

  • Pernicious anaemiathis can result from not enough vitamin B12. Thus it can result from destruction of oxyntic cells, which leads to insufficient secretion of intrinsic factor.


The alkaline tide

The production of hydrochloric acid can produce an alkaline tide. This is the relatively high level of bicarbonate found in the blood around the stomach during the production of stomach acid. In patients with severe vomiting, this can produce metabolic alkylosis. Oxyntic cells will take up CO2 from the blood. Once inside the cell, it will dissociate, in the presence of water and carbonic anhydrase to form H+ and HCO3-. The bicarbonate ions are exchanged for chloride ions in the blood, thus producing the outflux of bicarbonate, responsible for the alkaline tide. Remember with high levels of secretion of gastric juice, the juice is also more acidic, hence the exaggerated effect of the alkaline tide in persistent vomiting. Hydrogen ions are then pumped by an active process into the lumen of the gastric pit, by an ATPase that exchanges 1 hydrogen for 1 potassium. Chloride ions are also excreted actively in a process that exchanges them 1:1 with bicarbonate ions.

  • Note that it is the CFTR transported that brings in CL- from the blood, but it is not this transporter that transports it out into the lumen.

Intrinsic factor binds with vitamin B12, to form vitamin B12 complexes. These are then absorbed in the distal ileum.  Gastroferrin is another thing released by oxyntic cells. Iron can only be absorbed in its Ferrous (Fe2+) form and not its ferric (Fe3+) form. The acid of the stomach helps keep iron in its ferrous form, but also gastroferrin can bind to fe2+ and prevent it from forming other complexes with other ions, and thus help aid its absorption. Pepsinogen requires an acid environment to become active, and pepsin also requires an acid environment in which to act.

  • Pepsin and ulcers – pepsin is actually partly responsible for the formation of ulcers. In situations where the stomach lining is not properly protected, then pepsin can act on your own mucosa and digest it. PPI’s reduce the acidity of the stomach and thus reduce the action of pepsin, thus helping the mucosa to heal.
  • Pepsin potentiates, but does not initiate ulcer formation.
  • Remember though that most ulcers are in the duodenum, not in the stomach – and the duodenal mucosa in unprotected!

Mucous secretions not only are alkaline and thus help protect the mucosa, but they also help lubricate the food. Note that the mucous does not continually cover the whole of the gastric epithelium. The fact that the stomach also has an excellent blood supply can also help ‘protect’ it due to the fact it can heal very quickly.

  • Also remember that food itself buffers a lot of the acid in the stomach.

Absorption in the stomach – the stomach is pretty much impermeable to everything (including water) however, alcohol and aspirin are absorbed here.

  • Aspirin reduces prostaglandin secretion and thus reduces cell healing. However, this effect also reduces cell turnover, which is handy in the colon as it reduces the risk of colon cancer.

Control of gastric activity

  • This is mostly down to the effect of gastrin. This not only increases the rate of production of acid, but also ‘prepares’ the rest of the stomach for digestion. It is released in response to the presence of amino acids and peptides (mainly peptides) in the stomach. It is also released in response to nervous stimuli (i.e. caused by the presence of a bolus in the stomach, causing the release of ACh by the vagus nerves).
  • It is produced by G cells which are open APUD cells – open APUD cells are found all along the GIt and basically they are cells that sample the contents of the lumen and then release something in response to this.
    • Note that ‘closed’ APUD cells still secrete stuff (generally in an endocrine manner) but that they cannot respond to changing luminal contents because they don’t have receptors for this.
  • The turnover of G cells is quite slow – and is related to the level of acid in the stomach:
    • Rebound hyperacidity – when you give a PPI you reduce the amount of acid in the stomach. This will cause proliferation of G cells. this will cause an increase in the level of serum gastrin. Thus, when you stop the PPI, then your high levels of serum gastrin will lead to the overproduction of acid.
  • Gastrin will also cause increased expression of its own receptor on oxyntic cells, thus causing a ‘multiplying effect’.
  • Histamine – the release of histamine will also cause the release of gastric acid from oxyntic cells. It acts on H2 receptors on the oxyntic cells to cause the release of acid. it is released by ECL cells. The ECL cells can be stimulated by the presence of gastrin, or by ACh released by the vagus nerves.
  • Histamine causes secretions that are particularly rich in acid.
  • Somatostatin is released by D cells. Somatostatin will inhibit gastric acid secretion. It is released by D cells in response to gastrin, and thus this is a feedback mechanism to stop gastric acid secretion getting out of control. It is also released in very large amounts in response to H+ ions. Thus in very acid conditions it strongly inhibits gastric acid production. When the pH is less than 3 it is virtually impossible to stimulate gastric acid secretion.
    • Somatostatin acts in both paracrine and endocrine manners.
  • Note that CCK and gastrin have similar effects on stomach mucosa – thus everything that gastrin does, CCK does too – HOWEVER – CCK has a stronger effect on D cells than it does on other cells, and thus it probably actually reduces overall gastric acid secretion. CCk also has a weaker effect than gastrin on cells responsible for increased gastric acid production. Thus when it competitively binds on gastrin receptors it can prevent gastrin from doing so, and thus reduce the potential gastric acid output.
  • Nervous stimulation – generally cholinergic (ACh – vagus nerves) will cause an increase in motility and secretion, and adrenergic fibres (sympathetic chain) will have the opposite effect.
  • Secretin, GIP and VIP – these are all released by the duodenum, and all bind to the same gastric receptors. They basically inhibit gastric acid production.


  • The gastric cells have an oscillating membrane voltage. Then this reaches the threshold, then the cells will contract. This potential can be altered by stretch (the presence of food in the stomach), and also by nervous stimulation. These two factors will ensure the voltage goes over the threshold and causes contraction.
  • Sympathetic stimulation will hyperpolarise the membrane and thus result in reduced motility. Exercise has this effect!


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Dr Tom Leach

Dr Tom Leach MBChB DCH EMCert(ACEM) FRACGP currently works as a GP and an Emergency Department CMO in Australia. He is also a Clinical Associate Lecturer at the Australian National University, and is studying for a Masters of Sports Medicine at the University of Queensland. After graduating from his medical degree at the University of Manchester in 2011, Tom completed his Foundation Training at Bolton Royal Hospital, before moving to Australia in 2013. He started almostadoctor whilst a third year medical student in 2009. Read full bio

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