[RD5:p368]

• Acid is secreted from gastric parietal cells by a proton pump
• Endogenous secretagogues (which stimulate acid secretion)
  * Histamine (acting on H2 receptors)
  * Acetylcholine
  * Gastrin
• Prostaglandin E2 and I2:
  * Inhibit acid secretion
  * Stimulate mucus and bicarbonate secretion
  * Dilate mucosal blood vessels

 

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[WG21:p495]

Stomach

Parietal cells secretes HCl acid and intrinsic factors

Chief cells secrete pepsinogen

Innervation

Parasympathetic = from vagus

Sympathetic = from celiac plexus

 

G cells in antrum secretes gastrin

 

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[WG21:p496]

Secretion of gastric acid

When parietal cells are stimulated

• Insertion of H-K ATPase pump into the luminal membrane
  --> Exposure to K+ in stomach
  --> H+ is pump into stomach and K+ is taken into cell
• Cl- diffuse into stomach by channels activated by cAMP
• HCO3 diffuse out of basolateral membrane via HCO3-Cl antiporter
• K diffuse back into lumen or into blood
• Carbonic anhydrase present

 

 

Gastric acid secretion

[WG21:p497]

Stimulated by

• Histamine
  * via H2 receptors
  * Increasing cAMP via Gs protein
• ACh
  * via M3 muscarinic receptors
  * Increase intracellular [Ca2+]
• Gastrin
  * (Direcly) Increase intracellular [Ca2+]
  * (Indirectly, mainly) Stimulation of histamine release by ECL cells

Inhibited by

• Prostaglandins, especially E series
  * Via activating Gi proteins
  * e.g. PGE2
• Secretin
• Others: GIP VIP

ECL cells

Gastrin also acts by stimulating histamine secretion from enterochromaffin-like cells (ECL cells)

ECL cells have ACh receptors in addition to gastrin receptors

ECL cells are inhibited by somatostatin

 

Regulation of acid secretion

Neural and humoral

Vagal stimulation
--> Release gastrin-releasing peptide
--> Increase gastrin secretion

Some vagal fibres
--> Release ACh
--> Direct stimulation
--> Increase acid and pepsin secretion

 

Cephalic influences

Presence of food in mouth
--> Reflex stimulation

Efferent fibre = vagus nerve

Responsible for 1/3 to 1/2 of acid secreted in response to a normal meal

Others

Fear and depression decrease secretion

Anger and hostility increase secretion

 

Gastric influences

Receptors in the walls of stomach and mucosa respond to

1. Stretch
2. Chemical stimuli

Thus acid responses are by local reflex only

Products of protein digestion also increase secretion of gastrin

 

Intestinal influence

Fats, carbohydrates, and acid in the duodenum inhibits gastric acid and pepsin secretion and gastric motility
* via neural and hormonal mechanisms

 

Other influences

Hypoglycemia acts via brain and vagal efferent to stimulate acid and pepsin secretion

Alcohol and caffeine act directly on mucosa to stimulate acid production

 

NB:

• Food rich in carbohydrate leaves stomach in a few hours
• Protein-rich food leaves more slowly
• Fat-rich food = slowest

 

 

Other functions of stomach

Intrinsic factors binds to cyanocobalamin (vitamin B12)
--> Complex taken up by cubilin (apolipoprotein in receptors in distal ileum)
--> Endocytosis
--> In ileal enterocytes, cyanocobalamin transferred to transcobalamin II
--> Plasma