Physiology and Pharmacology of gastric motility and gastric acid secretion Flashcards
Which secretory cells are present in the gastric glands of the pyloric gland area of the stomach?
What do these cells produce?
G cells which produce gastrin, and D cells which produce somatostatin.
Both are peptide hormones.
Which secretory cells are present in the oxyntic mucosa gastric glands, and what do they produce?
Chief cells: produce pepsinogen
Parietal cells: produce HCl and intrinsic factor
Enterochromaffin-like cells: Produce histamine
Where in the stomach is a) the pyloric gland area and b) the oxyntic mucosa situated?
a) the antrum
b) the fundus and body
What are the functions of HCl?
Activates pepsinogen to pepsin by cleaving off an amino acid Denatures protein by unfolding the secondary structure, exposing the peptide bonds to be broken down by pepsin. Kills most (but not all) microorganisms ingested with food.
What is the function of pepsinogen?
This is the inactive precursor of pepsin. It is activated to pepsin by having an amino acid cleaved off, either by HCl, or active pepsin itself.
Pepsin is therefore autocatalytic.
What is the function of intrinsic factor?
It binds to vitamin B12 allowing it to be absorbed in the terminal ileum.
What is the function of histamine?
It stimulates HCl secretion.
What is produced in both the pyloric gland area and the oxyntic mucosa?
Mucous
What is the function of mucous?
Protects the epithelium
What is the function of gastrin?
It stimulates HCl secretion
What is the function of somatostatin?
It inhibits HCl secretion
Is Intrinsic factor produced anywhere else apart from the stomach?
No.
Describe the production and secretion of HCl by a parietal cell.
CO2 and H2O are combined under the action of carbonic anhydrase, to form carbonic acid.
Carbonic acid rapidly dissociates to form bicarbonate and a proton. The proton is actively pumped out of the cell into the canaliculus, via the H/K ATPase, in exchange for a K+ ion.
The K+ ion is recycled and enters the canaliculus through a specialised potassium channel.
The bicarbonate which was produced exits the cell via a chloride bicarbonate antiporter present on the basal lateral membrane of the cell, and enters the bloodstream.
In exchange, a chloride ion enters the cell via the same antiporter.
The chloride ion leaves the cell via a chloride channel, and joins up with an H+ in the canaliculus to form HCl.
Which receptors present on the parietal cell result in increased release of gastric acid via the H/KATPase?
What acts on each of these receptors?
M3 muscarinic receptor: ACh released from a postganglionic, parasympathetic cholinergic nerve
H2 histamine receptor: Histamine
Gastrin receptor: Gastrin
Where are gastrin receptors?
What is the effect of their stimulation?
Parietal cell: Increased acid secretion
Enterochromaffin-like cell: increased histamine secretion, leading to increased acid secretion from the parietal cell)
Which muscarinic receptor is present on a) the enterochromaffin-like cell and b) the parietal cell?
What is the effect of their stimulation?
a) M1 - increased release of histamine, leading to increased acid secretion from the parietal cell.
b) M3 - increased acid secretion.
What does somatostatin act on?
What is its effect?
It acts on G cells and inhibits the release of gastrin, thereby inhibiting the secretion of acid from the parietal cells.
a) What inhibits the H/KATPase?
b) Which drugs inhibit this?
a) Stimulation of the prostaglandin receptor on the parietal cell, by PGE2.
b) NSAIDs inhibit the formation of prostaglandins so inhibit this process.
Where are the H/KATPases when they are not needed?
They are located in tubulovesicles in the cytoplasm of the parietal cell.
When there is stimulation, the vesicles fuse with the membrane, increasing the membrane surface area and producing villi in the membrane lining the canaliculus. When they are at the membrane the pumps become activated and start actively pumping out H+.
What are the three phases of gastric secretion?
Cephalic, gastric, intestinal.
Describe the cephalic phase of gastric secretion.
The sight, smell or taste of food, as well as chewing and swallowing causes vagal activation, which causes excitatation of the enteric neurones (which are post-ganglionic parasympathetic neurones).
Enteric neurones can release ACh which:
acts directly on the parietal cell to cause an increase in H+ secretion.
Acts on ECL cells to cause an increase in histamine production.
Acts on D cells to inhibit the release of somatostatin.
The enteric neurone which innervates the G cell releases gastrin releasing pepsin, to stimulate the release of gastrin.
Describe the gastric phase of secretion.
In the gastric phase, both mechanical and chemical factors augment secretion.
Mechanoreceptors present in the smooth muscle wall of the stomach are stimulated by distension. This activates enteric neurones, which then increases acid secretion.
The G cells can also be activated by mechanoreceptors.
Protein digestion products have a direct effect on the G cell, further stimulating gastrin realease and acid secretion.
Describe the intestinal phase of secretion.
This phase reduces gastric secretions.
The same factors which reduce motility also reduce secretion: Fat, acid, hypertonicity, distension.
As the stomach empties, the stimuli for secretion become less intense.
Secretion of somatostatin now resumes (due to the low pH in the stomach lumen, which occurs between meals).
What drug classes influence gastric acid secretion? Give examples.
Muscarinic receptor antagonists e.g. pirenzipine.
H2 receptor antagonists e.g. ranitidine.
NSAIDs e.g. aspirin
Proton pump inhibitors e.g. omeprazole.
