Acid Secretion & PUD Flashcards
anatomy of the stomach
*cardia
*fundus
*body
*antrum
*pylorus
oxyntic glands
*located in the gastric BODY
-mucous neck cells
-parietal cells
-chief cells
-ECL cells
pyloric glands
*located in the gastric ANTRUM
-mucous cells
-G cells
parietal cells - functions
1) hydrochloric acid
-kills microorganisms
-cleaves pepsinogen to pepsin
-activates pepsin at pH < 4
2) intrinsic factor
-binds vitamin B12, which allows absorption in the terminal ileum
production of HCl by parietal cells
- carbonic anhydrase converts water + Co2 into carbonic acid
- carbonic acid dissociates into H+ and bicarb
- H+/K+ ATPase (proton pump) pumps H+ ions into gastric lumen, and chloride follows
- chloride-bicarbonate counter-transporter on the opposite (basolateral) membrane pumps bicarb into the blood
note - 3 inputs on the parietal cell stimulate the production of acid (acetylcholine, HISTAMINE, and gastrin)
what 3 inputs stimulate acid production by the parietal cell?
- HISTAMINE
- acetylcholine
- gastrin
chief cells - function
*SECRETE PEPSINOGEN
-cleaved to active form by HCl
-pepsin is a proteolytic enzyme
ECL cells - function
*SECRETE HISTAMINE (histamine stimulates the parietal cell to secrete HCl)
stimulation/inhibition of histamine release from ECL cells
*stimulated by: (1) gastrin; (2) acetylcholine (vagus)
*inhibited by: somatostatin
G cells - function
*SECRETE GASTRIN:
-gastrin stimulates ECL cells to release histamine and stimulates other oxyntic glands to secrete HCl and pepsinogens
stimulation/inhibition of gastrin release from G cells
*stimulated by: (1) gastric distension; (2) amino acids
*inhibited by: (1) somatostatin; (2) secretin; (3) gastric acid
D cells - function
*SECRETE SOMATOSTATIN
-somatostatin inhibits: (1) histamine release by ECL cells; (2) gastrin release by G cells; (3) inhibits HCl secretion by parietal cells
stimulation/inhibition of somatostatin release by D cells
*stimulated by: (1) acid; (2) CCK; (3) gastrin
*inhibited by: acetylcholine (vagus)
control of HCl secretion - AGONISTS
**HISTAMINE
control of HCl secretion - ANTAGONISTS
**SOMATOSTATIN
cephalic phase of acid secretion
*elicited by sight, smell, and taste of food
*entirely mediated by the VAGUS NERVE (stimulates parietal cells, ECL cells, and G cells; inhibits D cells)
*feedback inhibition: low gastric pH evokes inhibition of parietal cells & G cells
gastric phase of acid secretion
*once the food moves into stomach
*gastric distension (mechanoreceptors in the gastric wall initiate vasovagal reflexes)
*amino acids & peptides stimulate G cells to secrete gastrin
intestinal phase of acid secretion
*STIMULATION: duodenal distension initiates vasovagal reflex & peptides/amino acids stimulate duodenal G cells
*INHIBITION:
1) acid in the duodenum: inhibits the vasovagal reflex & releases secretin (inhibiting acid secretion)
2) ingested fat & protein in the duodenum releases CCK (inhibiting acid secretion)
mucosal protection of the stomach
*mucus secretion
*bicarbonate secretion
*epithelial barrier
*mucosal blood flow
causes of peptic ulcer disease
1) H. pylori (helicobacter pylori)
2) NSAIDs
H. pylori - overview
*small, gram negative rod with flagella
*colonizes the mucous layer (NOT invasive)
*elaborates UREASE (produces ammonia and thereby neutralizes acid)
H. pylori & gastric malignancy
associated with:
*gastric adenocarcinoma
*MALT lymphoma
tests used to diagnose H. pylori infection
**urea breath test!
**stool antigen assay!
other: biopsy urease test (CLO), histology, culture, serology
action of NSAIDs
*inhibition of cyclo-oxygenase enzymes (COX-1 and COX-2)
*COX-1: produces PROSTACYCLIN (important for protection of gastric mucosa)
*COX-2: induced by inflammation and cytokines
effects of NSAIDs on the gastric mucosa
*decrease mucosal blood flow
*decrease mucous production
*decrease bicarbonate production
*may increase secretion of acid and pepsin
OVERALL, put you at increased risk of developing peptic ulcers
COX-2 inhibitors - therapeutic advantage
*inhibition of COX-2 results in desired effects of decreased inflammation
*inhibition of COX-1 (most NSAIDs inhibit both 1 & 2) results in undesired effects of GI toxicity
stress & peptic ulcer disease
*seen only in extremely sick patients (trauma, burns, head injuries, ventilator patients)
*related to alpha-adrenergic mediated decrease in mucosal blood flow
complications of peptic ulcer disease
*pain
*bleeding
*perforation
*gastric outlet obstruction
acid reduction interventions for treating peptic ulcer disease
*acetylcholine (anticholinergics, vagotomy)
*histamine (H2 RECEPTOR ANTAGONISTS)
*gastrin (antrectomy)
*PROTON PUMP INHIBITORS
famotidine - drug class
H2 receptor antagonist (H2 blocker)
famotidine - MOA
*H2 receptor antagonist
*blocks parietal cell histamine receptor
famotidine - drug action/use
*decreases histamine-stimulated parietal cell H+ secretion
*short-duration gastric acid reduction
famotidine - side effects
*diarrhea
*headache
proton pump inhibitors to know
*omeprazole
*pantoprazole
omeprazole - drug class
proton pump inhibitor
omeprazole - MOA
bind and irreversibly inactivate parietal cell H+/K+ ATPase
omeprazole - drug action/use
*decreases all-stimulus parietal cell H+ secretion
*long-acting gastric acid reduction
*accelerate mucosal healing in PUD
omeprazole - side effects
*headache, nausea, diarrhea
*increased long-term risk of: vitamin B12 deficiency, hypomagnesemia, SIBO, osteoporosis, renal insufficiency?
pantoprazole - drug class
proton pump inhibitor
pantoprazole - MOA
bind and irreversibly inactivate parietal cell H+/K+ ATPase
pantoprazole - drug action/use
*decreases all-stimulus parietal cell H+ secretion
*long-acting gastric acid reduction
*accelerate mucosal healing in PUD
pantoprazole - side effects
*headache, nausea, diarrhea
*increased long-term risk of: vitamin B12 deficiency, hypomagnesemia, SIBO, osteoporosis, renal insufficiency?
mucosal protection interventions for treating peptic ulcer disease
*misoprostol
*sucralfate
misoprostol
*drug class: mucosal protectant
*MOA: prostaglandin E1 synthetic analog
*drug action/use: decreased acid by inhibition of adenylate cyclase
*side effects: CONTRAINDICATED IN PREGNANCY, diarrhea, nausea, abdominal pain
sucralfate
*drug class: mucosal protectant
*MOA: ionic binding to damaged tissue
*drug action/use: mucosal coating action; weak bile acid binder
*side effects: constipation and nausea
