gastric acid secretion pharmacology and physiology

Question 1

what regulates the movement of food in the stomach?

Answer 1

the cardiac sphincter at the top of the stomach and the pyloric sphincter at the base - these control the movement of food in and out of the stomach.

Question 2

what cells make up the stomach wall?

Answer 2

a range of cells including parietal cells, mucous cells, D cells, ECL cells. enterochromaffin like cells are stiumlated by activation of gastrin receptors by gastrin thats prouced by the g cells of the stomach wall. the g cells are under neuronal contol but food also stimulates them to release gastrin.

Question 3

how does the parietal cell produce H+?

Answer 3

metabolic co2 and h2o in the cytoplasm of the parietal cell react with the aid of carbonic anhydrasee to form bicarbonate acid h2co3 - this then dissociates into hco3- and h+
- the bicarbonate is antiported against chloride through the basolateral membrane into the blood.
- a symport carrier secretes chloride alongside K+ accross the apical membrane into the lumen of the stomach.
- a proton pump exchanges potassium for protons accross the apical membrane hence H+ enters the lumen of the stomach - this requires energy/atp.
the hydrogen and chloride excreted into the stomach form hcl- this acid solution kills bacteria and optimises digestion of food by pepsin

Question 4

what stimulates the parietal cell?

Answer 4

• enteric neurons release acetylcholine which acts on m3 receptors of the parietal cell activating hcl secretion - this is stimulated by parasympathetic activity in response to food - sight taste and smell. - distension of the stomach activates neural reflexes so enteric neurons release ACh.
• gastrin released from g cells (a specialised endocrine epithelial cell in the gastric epithelium) stimulates enterochromaffin like cells to release histamine which acts on h2 receptors of the parietal cell triggering hcl release. - peptides activate the g cells.

Question 5

what inhibits gastric acid release?

Answer 5

somatostatin is released from endochrine epithelial cells in response to stomach acid levels in a negative feedback pathway.
acid secretion is inhibited by intestinal phase stimuli includong increased H+, distension, osmolarity and fats in the duodenum. this inhibits both the neural and hormonal reflex

Question 6

what happens when gastric acid is neutralised by food in the stomach?

Answer 6

the release of somatostatin falls so that it will no longer inhibit the release of HCl.

Question 7

how is the stomach linig protected from acid ?

Answer 7

mucus - mucus is a colloidal gel polymer of hydrated mucin glygoproteins thats secreted by surface mucous epithelial cells. it generates a continous alkaline mucuc barrier that overlays the epithelial lining, protecting it from acid and pepsin. the production of mucus is under hormonal control.

Question 8

whats a peptic ulcer?

Answer 8

a common condition in which there is a lesion in the stomach wall/duodenum which starts to get digested by exposure to acid.

Question 9

what are symptoms of a peptic ulcer?

Answer 9

heartburn, abdominal pain, bloating, nausea, vomiting, bloody vomit, melena (black stool due to iron from bleeding gi tract), peritonitis.

Question 10

what are peptic ulcers associated with?

Answer 10

helicobacter pykori, chrinic nsaid use, smoking and stress.

Question 11

what is gord?

Answer 11

gastro osophageal reflux disease is a common condition where acid from the stomach leaks up into the oesophagus.

Question 12

what are the symptoms of gord?

Answer 12

heartburn, acid reflux, oesophagitis, bloating and belchinf, nausea and pain when swallowing.

Question 13

what are some of the complications of gord?

Answer 13

ulceration, scarring, barrets oesophagus - acid alters the epithelium increasing the risk of cancer

Question 14

what happens if a patient has an ulcer due to h.pylori?

Answer 14

h.pylori is a common bacterium that thrives in acid environment, its strongly associated with ulceration and increased stomach cancer risk. if this bacteria is causing the peptic ulcer we must eradicate it to reduce recurrence of ulcers. common antibiotics are amoxicillin, metronidazole and clarithromycin. another treatment is bismuth chelate - this has a toxic effect on bacteria inhibiting bcterial proteases and adhesion

Question 15

how can antacids be used?

Answer 15

antacids neutralise the stomach acid. they usually use a bicarbonate that will buffer the hydrogen out of the stomach.

Question 16

what are some common antacids?

Answer 16

sodium bicarbonate, calcium carbonate and magnesium/aluminium hydroxide - magnesium can cause osmotic diarrhoea whilst aluminium can cause constipation - they should therefore be used together.
magnesium trisilicate is an insoluble powder that slowly reacts with the acid to form magnesium chloride and colloidal silica - these have a prolonged effect.

Question 17

how can a muscarinic antagonist inhibit acid secretion?

Answer 17

pirenzapine is an m1 selective antagonist, it binds to m1 receptors on g cells inhibiting the vagus induced release of histamine. however as the parietal cell also has m3 receptors that are directly stimulated by ach m3 mediated acid release is still possible.
atropine can be used to block m3 receptors

Question 18

how can h2 receptor antagonists be used to inhibit acid secretion?

Answer 18

histamine released from enterochromaffin like cells act on h2 receptors of the parietal cells as a potent stimulant of gastric acid secretion. blocking the h2 receptors with antagonist like cimetidine will inhibit the histamine mediated release of acid. however cimetidine has many interactions like: cyp inhibitor, reduces renal clearance, decreases hepatic blood flow - h2 antagonists with fewer interactions include ranitidine and famitidine.

Question 19

how do ppis inhbit acid secretion?

Answer 19

ppis irreversibly block proton pumps in the parietal cells via covalent binding hence directly inhibiting acid secretion. ppis are given as prodrugs that become activated in the acid environment - examples are lansoprazole and omeprazole.
ppis are more effective as they block the end stage secretion of h+. the oral dosage form is in an enteric capsule to avoid drug activation in the stomach before recahing the parietal cell. they are then absorbed into the blood in the small intestine, from systemic circulation it will effect the tissue side of the stomach. it accumulates in the acid environment of the parietal cell canaliculi, here it gets activated and irreversibly blocks the proton pump hence it has prolonged action.

Question 20

what are cytoprotective drugs?

Answer 20

cytoprotective drugs enhance the mucosal barrier.

Question 21

how do alginates wok?

Answer 21

theyre a cytoprotective drug - alginates precipitate in the presence of gastric acid forming a gel that localises to the acid pocket in the stomach.

Question 22

how does sucralfate work?

Answer 22

sucralfate is a cytoprotective drug - it is a complex that releases aluminium in acid to leave a negativily charged complex, this will then bind glycoproteins decreasing mucus degradation, stimulates mucus bicarbonate and PG secretion and reduces the absorption of therapeutic drugs.

Question 23

whats the physiological function of prostaglandins?

Answer 23

• inhibition of gastric acid secretion and increased mucus production (PGE2)
• vascular via PGI2 from endothelium causes inhibition of platelet aggregation and vasodilation
• vascular via TxA2 from platelets causes platelet aggregation and vasoconstriction

Question 24

what are prostaglandin analogues?

Answer 24

prostaglandin analogues like misoprostol (orally active PGE1 analogue) can be used to treat peptic ulcers, these have different effects via different E-prostaglandin receptor subtypes on different target cells.

Question 25

What do prostaglandin analogues do in the stomach?

Answer 25

reduce gastric acid and pepsin secretion via inhibition of enterochromaffin like cells.

• stimulate mucus and bicarbonate secretion by the endothelium
• increase mucosal blood flow by dilater action on arterioles - increased blood flow helps clear the acid.

Question 26

how can nsaids lead to ulceration?

Answer 26

nsaids like aspirin, indomethacin and ibuprofen inhibit the production of prostaglandins which can excacerbate/cause gastric ulcers. this occurs due to:

• direct irritation of stomach lining
• inhibit prostaglabdin production via cox removing the cytoprotective effects of prostaglandin and decreasing platelet aggregation causing increased bleeding.

Question 27

why would celecoxib spare the stomach?

Answer 27

celecoxib is a selective cox 2 inhibitor - stomach pg production is mainly by the cox-1 isoform hence celecoxib would not affect this.