Ulcers

Question 1

what are the gastric receptors

Answer 1

parietal cells
mucous cells
ECL cells
D cells

Question 2

parietal cell H+ secretion

Answer 2

carbonic acid is generated by carbonic anhydrase and is a source of H+ and bicarbonate
bicarbonate antiported against Cl- across basolateral membrane
Proton pump for H+/K+ATPase
Cl- is secreted alongside K+ by symport carrier

Question 3

gastric acid secretion

Answer 3

parietal cells secrete large volumes of HCl into the stomach (gives pH optimal for pepsin activity)

Question 4

what stimulates acid secretion from parietal cells

Answer 4

ACh from nerves acting on M3 receptors which have been stimulated by vagus nerve in response to food triggers
also stimulated by histamine from ECL cells acting on H2 receptors
also stimulated by gastrin from G epithelial cells

Question 5

what does ECL stand for

Answer 5

enterochromaffin-like cells

Question 6

summary of acid secretion process

Answer 6

G cell -> gastrin -> ECL cell -> histamine -> parietal cell

Question 7

what inhibits acid secretion

Answer 7

somatostatin from endocrine epithelial cells
they are responsive to stomach acid levels and operate via a negative feedback pathway
food neutralises gastric acid as somatostatin release falls

Question 8

what is the mucous barrier made of

Answer 8

gel polymer of hydrated mucin glycoproteins that are secreted by surface mucous epithelial cells
creates continuous alkaline mucous barrier that protects the stomach lining from acid and pepsin

Question 9

symptoms of peptic ulcer

also associated with h-pylori infection, NSAID use, stress, smoking

Answer 9

heartburn, abdominal pain, bloating, nausea, vomiting, bloody vomit, melena, peritonitis

Question 10

what is GORD

Answer 10

gastro-oesophageal reflux disease

Question 11

what are the symptoms of GORD

Answer 11

heartburn, acid-reflux, oesophagitis, nausea, bloating, belching, pain on swallowing

Question 12

complications of GORD

Answer 12

ulceration, scarring, cancer

Question 13

treatment of peptic ulcer by eradication of h-pylori

Answer 13

abx therapy (amoxicillin, metronidazole, clarithromycin)
bismuth chelate has a toxic effect on bacteria and inhibits bacterial adhesion and bacterial proteases

Question 14

use of an antacid to treat peptic ulcer

Answer 14

they neutralise stomach acid (Mg or Al OH - OH binds to H+ and gives osmotic diarrhoea or constipation) it absorbs pepsin and sodium bicarbonate allows HCO3- to buffer H+. Calcium carbonate and magnesium triscilate also used

Question 15

treatment of peptic ulcer

Answer 15

H2 antagonists and PPIs used

Question 16

what are muscarinic antagonists

Answer 16

M1 selective antagonists no longer used to treat peptic ulcers
inhibit vagus-induced histamine and release/block M1 on G cells but acid can still be released via M3
no effect on smooth muscle or BBB

Question 17

what are H2 receptor antagonists

Answer 17

block histamine released by ECL

block H2 receptors on parietal cells which are potent stimulators of gastric acid secretion

Question 18

what is cimetidine

Answer 18

CYP inhibitor and causes reduced renal clearance and decreased hepatic blood flow
increased absorption of acid-lible drugs due to its effect on gastric pH

Question 19

action of PPIs

Answer 19

irreversibly block H+/K+ATPase pump in gastric parietal cells by covalently bonding
given as prodrugs and activated in the acidic environment to prevent H+ secretion
absorbed in small intestine into blood and accumulate in the acid environment of parietal cell canaliculi

Question 20

what are cytoprotective drugs

Answer 20

used to treat peptic ulcers
they enhance the mucosal barrier
they are alginates that increase viscosity and tenacity of mucous

Question 21

what is sucralfate

Answer 21

Al(OH)3 (a sulfated sucrose complex) that releases Al into the acid ro leave a negatively charged complex that binds glycoproteins and decreases mucous degredation
stimulates mucous, bicarbonate and PG secretion and reduces absorption of therapeutic drugs

Question 22

prostaglandin analogues

Answer 22

e.g. misoprostol
can reduce gastric acid and pepsin secretion due to inhibition of ECL cell, stimulates mucous and bicarbonate secretion by epithelium, increases mucosal blood flow by dilating arterioles

Question 23

physiological functions of prostaglandins

Answer 23

inhibits gastric acid secretion, increased gastric mucous production, vascular effects that inhibit platelet aggregation and vasdilation, could also cause platelet aggregation and vasoconstriction

Question 24

NSAIDs action

Answer 24

block production of prostaglandins and their overuse leads to gastril ulceration
act on COX to inhibit prostaglandins and decrease platelet aggregation which causes bleeding
celecoxib is a selective COX2 inhibitor that spares the stomach lining