Let’s talk about the stomach! Part 2

I think it’s time to link the anatomy of the stomach to it’s physiology, particularly acid production and regulation. Due to the end-of-term deadlines and coursework I haven’t been able to write or revise much, however tonight is the night I go back and revisit my notes on digestion. Again, I’ll be equipped with my own diagrams.

Physiology? Let’s back up for a bit.. Where does acid come from?

Main physiological function of the stomach is to produce hydrochloric acid (HCl) and this is exactly what we will be talking about in this post. It is secreted alongside other substances such as pepsin, intrinsic factor and gastric lipase, forming gastric juice. From histology we know that the mucosa (lining) is arranged into gastric pits. The epithelial cells extend down into lamina propria (layer of connective tissue) where they form columns of secretory cells called gastric glands. These glands contain exocrine (secretion into lumen) and enteroendocrine (secretion into bloodstream) cells.

Well, what are those?

  • Exocrine:
    • Mucous neck cells and surface mucous cells (throughout the stomach) produce mucous. This is a bicarbonate-rich solution that lines the mucosa and neutralises the low pH. Without it, you would get severe stomach ulceration and auto-digestion and that doesn’t sound very appealing.
    • Parietal cells* (fundus) secrete intrinsic factor (important for B12 absorption) and produce HCl acid.
    • Chief cells (fundus) secrete pepsinogen and gastric lipase.

These exocrine substances make up gastric juice, which we secrete around 2000-3000 ml/day.

  • Enteroendorine:
    • G cells (antrum) secrete a hormone called gastrin.
    • D cells (antrum) secrete somatostatin.


Okay, so how does it actually happen?

2015-12-11 20.53.45

Figure 1: Secretion of HCl by a parietal* cell

Secretion of HCl happens at the fundus and this is quite interesting because the acid runs down the walls of the stomach and is mixed into food by mixing waves (peristalsis).

The equation in the middle is important as it provides two types of ions for different exchange mechanisms. The binding of water (H2O) with carbon dioxide (CO2) and carbonic acid (H2CO3) formation is catalysed by carbonic anhydrase. As H2CO3 dissociates, it provides H+ and HCO3- for proton pumps and Cl-/HCO3- exchanges.


  • Proton pumps (H+/K+ ATPases) actively transport H+ into lumen and bring K+ into the cell.
  • This happens at the same time as the Cl- and K+ diffuse out through Cl- and K+ specialised channels in the apical membrane (refer to the diagram).
  • HCO3- exits parietal cell via HCO3-/Cl- antiporters in basolateral membrane exchange.
  • H+ and Cl- combine and produce the net result of HCl.


Secretion is stimulated by:

  • Stomach distension and protein in the food.
  • Parasympathetic nervous system (vagus nerve) by:
    • Acetylcholine (directly) via M3 receptor.
    • Gastrin releasing peptide (indirectly) via G cells and gastrin.
  • G cells 
    • Gastrin secretion into the blood which:
      • directly links with the parietal cells via CCKb (Cholecystokinin B) receptor.
      • indirectly links to ECL (enterochromaffin-like) cells via CCKb receptor.
  • ECL cells
    • releases histamine which directly links to parietal cell via H2 receptor and enhances effects of ACh and gastrin.


How is this all regulated?

This is not as complicated as the above information. Take it all in, stop crying, go make yourself a cup of tea, we are almost done.

Gastric acid regulation has 3 phases:

  1. Cephalic – initiated by smell/taste (food is the ultimate weapon) and mediated by parasympathetic system.
  2. Gastric – initiated in the stomach by distension and protein. Also mediated by gastrin via direct and indirect action (we covered this 2 minutes ago).
  3. Intestinal :
    1. Stimulatory when there is protein in the duodenum which then initiates gastrin release.
    2. Inhibitory when:
      1. pH is lower due to excess fat.
      2. secretin is in action.
      3. somatostatin is secreted.


For eccentric people who want even more information about the stomach (seriously, who would do this) I’ll post some useful links under resources. Until next time!



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