Physiology and Pharmacology of gastric motility and gastric acid secretion Flashcards Preview

GI > Physiology and Pharmacology of gastric motility and gastric acid secretion > Flashcards

Flashcards in Physiology and Pharmacology of gastric motility and gastric acid secretion Deck (30):

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?



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?



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.


How is the mucosa protected from attack by pepsin and HCl?

There is a mucous gel layer on top of the epithelial cells. This means that the pH at the cells is more likely to be in the region of pH 7 than a low pH like in the lumen.
This is reinforced by the presence of HCO3 in the gel layer, which also neutralises any H+ ions that get into the layer.
On top of the layer there is a hydrophobic monolayer which also prevents H+ from reaching the mucous layer and the cells.
Locally produced prostaglandins PGE2 and PGI2 reduce acid secretion, increase mucous and bicarbonate secretion, and increase mucosal blood flow.


What is a peptic ulcer?

An ulcer in any area where the mucosa is exposed to hydrochloric acid and pepsin (i.e. the stomach and duodenum)


Which drugs may trigger this?

NSAIDs, because they block prostaglandin formation by blocking COX-1.
COX2 selective inhibitors may avoid this problem but they are associated with an increased risk of MI and stroke and several are withdrawn.


Which drugs can prevent gastric damage due to long term NSAID treatment?

PGE1 analogues e.g. misoprostol, which mimics the effects of PGE1.


Which bacteria can infect the stomach and cause a peptic ulcer?
Where in the stomach does it infect?
How does it cause an ulcer?

Helicobacter pylori
It infects the antrum.

The bacterium is mobile because it has flageallae. This means it can propel itself into the mucous gel layer, so it is protected from the enzymes and acid in the stomach layer.
When it is in the gel, H. pylori secretes agents which cause persistent inflammation which weakens the mucosal barrier.
Breakdown of the mucosal barrier damages the mucosal cell layer and leaves the submucosa and deeper layers subject to attack by HCl and pepsin.
Could get rupture of the stomach.


How does drug treatment of a peptic ulcer promote healing?

It reduces acid secretion
Increases mucosal resistance
Eradicates H. pylori.

Decks in GI Class (59):