Ulcers Flashcards
what are the gastric receptors
parietal cells
mucous cells
ECL cells
D cells
parietal cell H+ secretion
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
gastric acid secretion
parietal cells secrete large volumes of HCl into the stomach (gives pH optimal for pepsin activity)
what stimulates acid secretion from parietal cells
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
what does ECL stand for
enterochromaffin-like cells
summary of acid secretion process
G cell -> gastrin -> ECL cell -> histamine -> parietal cell
what inhibits acid secretion
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
what is the mucous barrier made of
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
symptoms of peptic ulcer
also associated with h-pylori infection, NSAID use, stress, smoking
heartburn, abdominal pain, bloating, nausea, vomiting, bloody vomit, melena, peritonitis
what is GORD
gastro-oesophageal reflux disease
what are the symptoms of GORD
heartburn, acid-reflux, oesophagitis, nausea, bloating, belching, pain on swallowing
complications of GORD
ulceration, scarring, cancer
treatment of peptic ulcer by eradication of h-pylori
abx therapy (amoxicillin, metronidazole, clarithromycin) bismuth chelate has a toxic effect on bacteria and inhibits bacterial adhesion and bacterial proteases
use of an antacid to treat peptic ulcer
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
treatment of peptic ulcer
H2 antagonists and PPIs used
what are muscarinic antagonists
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
what are H2 receptor antagonists
block histamine released by ECL
block H2 receptors on parietal cells which are potent stimulators of gastric acid secretion
what is cimetidine
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
action of PPIs
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
what are cytoprotective drugs
used to treat peptic ulcers
they enhance the mucosal barrier
they are alginates that increase viscosity and tenacity of mucous
what is sucralfate
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
prostaglandin analogues
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
physiological functions of prostaglandins
inhibits gastric acid secretion, increased gastric mucous production, vascular effects that inhibit platelet aggregation and vasdilation, could also cause platelet aggregation and vasoconstriction
NSAIDs action
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
