Where are gastric secretions produced? Name the 4 cell types found in this area and their secretions
1) Chief cells - pepsinogen
2) Parietal cells - HCl
3) Neck cells - Mucus and alkali
4) G cells - Gastrin
How is pepsinogen activated?
Activated by acid produced by parietal cells
Explain the mechanism of secretion of stomach acid. What happens to the alkali?
Acid produced in parietal cells.
Parietal cells have high density of mitochondria which produces protons.
Canaliculi in the cells have proton pumps that secrete protons into the lumen of the stomach.
Alkali enters the blood and neutralises the acid in the duodenum.
What 3 factors act on parietal cells to stimulate acid secretion?
• Gastrin – Hormone
How does gastrin function?
• Binds to surface receptor on parietal cell
• Stimulates acid and intrinsic factor (critical for absorption of vit b12) secretion via secondary messenger pathway
How does histamine act on parietal cells? Where is it released from?
• Released from Mast cells
• Binds to H2 surface receptors on the parietal cells
• Stimulates acid secretion via cAMP.
How does ACh act on parietal cells? Where is it released from? What blocks its action?
• Released from parasympathetic neurones
• Acts on muscarinic receptors
• Stimulates acid secretion by secondary messenger pathway
• Blocked by atropine
What stimulates and inhibits gastrin secretion?
• Peptides in the lumen
• Ach released by nerves which are activated by the physical distension of the stomach
• Low pH in the stomach, important when there is no food in your stomach
Why does blocking H2 receptors reduce acid secretions?
Histamine amplifies the effect of other messengers, therefore blocking histamine stops the amplification of the gastrin and ACh signal
What stimulates mast cells?
Gastrin and ACh
What occurs in the cephalic phase of gastric secretion?
The detecting and ingesting of food results in parasympathetic nerve stimulation, resulting in acid production in the stomach before food is ingested.
What occurs in the gastric phase of gastric secretion?
• Food reaches the stomach and soaks up the hydrogen ions, so pH rises, disinhibiting gastrin
• Stomach actively relaxes to prevent pressure build up. Stretch receptors detect stretch and release Ach which stimulates more acid.
• Initial digestion releases peptides which stimulates more gastrin release.
• Ulcers hurt more at night due to acid build up without food to soak up the hydrogen ions.
What stimulates ACh release?
distension of stomach
What occurs in the intestinal phase of gastric secretion?
• Stomach begins to empty
• Accumulation of acid in empty stomach inhibits gastrin secretion.
• Chyme stimulates release of hormones from intestines which antagonise gastrin.
Name 2 methods of reducing gastric acid secretion and their associated drug
Cimetidine – H2 receptor antagonist
Omeprazole (PPI) – proton pump inhibitors, even better.
What is the luminal pH of the stomach
less than 2
Explain how mucus protects the stomach for autodigestion.
Physical protection comes from mucus, mixtures of mucopolysaccharides, which are very sticky. This means that it adheres very tightly to the surface of the mucosa, exhibiting thixotropic property (forming a gap in the mucus means mucus will flow to fill the gap).
Mucus is basic and absorbs hydrogen ions:
• As hydrogen ions diffuse into the mucus they will eventually fill up the amine groups and overwhelm the buffering capacity
• However, due to stickiness an unstirred layer is formed which hydrogen ions find very difficult to diffuse through.
• Slow passage through unstirred layer allows hydrogen carbonate produced by the cells to neutralise the acid without it overwhelming the cells.
• CO2 produced, hence belching.
• Cells underneath tough enough to withstand pH of 6.
What stimulates mucus and alkali secretions in the stomach?
Mucus and alkali secretion stimulated by prostaglandins which are promoted by most of the factors stimulating acid secretion.
How does alcohol damage the stomach?
Alcohol dissolves the mucus. results in peptic ulcers
How does H. pylori damage the stomach?
H. pylori gets into mucosa and prevents mucosa from defending itself, results in ulcers
How does NSAIDS damage the stomach?
• NSAIDS inhibit prostaglandins and therefore reduce defences, e.g. aspirin which is converted into a non ionised form by stomach acid and then passes into the cells and re-ionises, killing them.
• Result of it all is peptic ulcers
Explain the concept of receptive relaxation of the stomach, why it occurs, what triggers it, and what happens if you damage the vagus nerve
• Triggered by swallowing, which results in a neural reflex.
• Tension in resting stomach wall is actively relaxed
• Pressure therefore doesn’t build.
• If vagus nerve damaged you can’t get receptive relaxation and therefore can’t eat large volumes of food
What drives the contractions of the stomach and how often does it fire?
Pacemaker in the cardiac region of the stomach. 3 times a minute.
Describe the process which results in chyme being squirted into the duodenum.
o Due to wide to narrow nature of stomach, initially the wave of AP proceeds slowly, propelling before it the entire contents of the stomach towards the antrum
o As it moves past the widest part of the stomach it narrows and therefore starts to accelerate
o This leaves behind the lumps and propels forward the liquid, only propelling chyme towards the pyloric canal.
o A small squirt is then ejected and the wave reaches the pylorus and shuts it o The rest of the chyme returns to the stomach
What affects the volume of each squirt of chyme into the duodenum?
o Rate of acceleration of peristaltic wave
o Hormones from intestine
What 3 factors slow gastric emptying?
o Fat in duodenum
o Low pH in duodenum
o Hypertonicity in duodenum