Acid Secretion & PUD

Question 1

anatomy of the stomach

Answer 1

*cardia
*fundus
*body
*antrum
*pylorus

Question 2

oxyntic glands

Answer 2

*located in the gastric BODY
-mucous neck cells
-parietal cells
-chief cells
-ECL cells

Question 3

pyloric glands

Answer 3

*located in the gastric ANTRUM
-mucous cells
-G cells

Question 4

parietal cells - functions

Answer 4

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

Question 5

production of HCl by parietal cells

Answer 5

1. carbonic anhydrase converts water + Co2 into carbonic acid
2. carbonic acid dissociates into H+ and bicarb
3. H+/K+ ATPase (proton pump) pumps H+ ions into gastric lumen, and chloride follows
4. 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)

Question 6

what 3 inputs stimulate acid production by the parietal cell?

Answer 6

1. HISTAMINE
2. acetylcholine
3. gastrin

Question 7

chief cells - function

Answer 7

*SECRETE PEPSINOGEN
-cleaved to active form by HCl
-pepsin is a proteolytic enzyme

Question 8

ECL cells - function

Answer 8

*SECRETE HISTAMINE (histamine stimulates the parietal cell to secrete HCl)

Question 9

stimulation/inhibition of histamine release from ECL cells

Answer 9

*stimulated by: (1) gastrin; (2) acetylcholine (vagus)
*inhibited by: somatostatin

Question 10

G cells - function

Answer 10

*SECRETE GASTRIN:
-gastrin stimulates ECL cells to release histamine and stimulates other oxyntic glands to secrete HCl and pepsinogens

Question 11

stimulation/inhibition of gastrin release from G cells

Answer 11

*stimulated by: (1) gastric distension; (2) amino acids
*inhibited by: (1) somatostatin; (2) secretin; (3) gastric acid

Question 12

D cells - function

Answer 12

*SECRETE SOMATOSTATIN
-somatostatin inhibits: (1) histamine release by ECL cells; (2) gastrin release by G cells; (3) inhibits HCl secretion by parietal cells

Question 13

stimulation/inhibition of somatostatin release by D cells

Answer 13

*stimulated by: (1) acid; (2) CCK; (3) gastrin
*inhibited by: acetylcholine (vagus)

Question 14

control of HCl secretion - AGONISTS

Answer 14

**HISTAMINE

Question 15

control of HCl secretion - ANTAGONISTS

Answer 15

**SOMATOSTATIN

Question 16

cephalic phase of acid secretion

Answer 16

*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

Question 17

gastric phase of acid secretion

Answer 17

*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

Question 18

intestinal phase of acid secretion

Answer 18

*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)

Question 19

mucosal protection of the stomach

Answer 19

*mucus secretion
*bicarbonate secretion
*epithelial barrier
*mucosal blood flow

Question 20

causes of peptic ulcer disease

Answer 20

1) H. pylori (helicobacter pylori)
2) NSAIDs

Question 21

H. pylori - overview

Answer 21

*small, gram negative rod with flagella
*colonizes the mucous layer (NOT invasive)
*elaborates UREASE (produces ammonia and thereby neutralizes acid)

Question 22

H. pylori & gastric malignancy

Answer 22

associated with:
*gastric adenocarcinoma
*MALT lymphoma

Question 23

tests used to diagnose H. pylori infection

Answer 23

**urea breath test!
**stool antigen assay!

other: biopsy urease test (CLO), histology, culture, serology

Question 24

action of NSAIDs

Answer 24

*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

Question 25

effects of NSAIDs on the gastric mucosa

Answer 25

*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

Question 26

COX-2 inhibitors - therapeutic advantage

Answer 26

*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

Question 27

stress & peptic ulcer disease

Answer 27

*seen only in extremely sick patients (trauma, burns, head injuries, ventilator patients)
*related to alpha-adrenergic mediated decrease in mucosal blood flow

Question 28

complications of peptic ulcer disease

Answer 28

*pain
*bleeding
*perforation
*gastric outlet obstruction

Question 29

acid reduction interventions for treating peptic ulcer disease

Answer 29

*acetylcholine (anticholinergics, vagotomy)
*histamine (H2 RECEPTOR ANTAGONISTS)
*gastrin (antrectomy)
*PROTON PUMP INHIBITORS

Question 30

famotidine - drug class

Answer 30

H2 receptor antagonist (H2 blocker)

Question 31

famotidine - MOA

Answer 31

*H2 receptor antagonist
*blocks parietal cell histamine receptor

Question 32

famotidine - drug action/use

Answer 32

*decreases histamine-stimulated parietal cell H+ secretion
*short-duration gastric acid reduction

Question 33

famotidine - side effects

Answer 33

*diarrhea
*headache

Question 34

proton pump inhibitors to know

Answer 34

*omeprazole
*pantoprazole

Question 35

omeprazole - drug class

Answer 35

proton pump inhibitor

Question 36

omeprazole - MOA

Answer 36

bind and irreversibly inactivate parietal cell H+/K+ ATPase

Question 37

omeprazole - drug action/use

Answer 37

*decreases all-stimulus parietal cell H+ secretion
*long-acting gastric acid reduction
*accelerate mucosal healing in PUD

Question 38

omeprazole - side effects

Answer 38

*headache, nausea, diarrhea
*increased long-term risk of: vitamin B12 deficiency, hypomagnesemia, SIBO, osteoporosis, renal insufficiency?

Question 39

pantoprazole - drug class

Answer 39

proton pump inhibitor

Question 40

pantoprazole - MOA

Answer 40

bind and irreversibly inactivate parietal cell H+/K+ ATPase

Question 41

pantoprazole - drug action/use

Answer 41

*decreases all-stimulus parietal cell H+ secretion
*long-acting gastric acid reduction
*accelerate mucosal healing in PUD

Question 42

pantoprazole - side effects

Answer 42

*headache, nausea, diarrhea
*increased long-term risk of: vitamin B12 deficiency, hypomagnesemia, SIBO, osteoporosis, renal insufficiency?

Question 43

mucosal protection interventions for treating peptic ulcer disease

Answer 43

*misoprostol
*sucralfate

Question 44

misoprostol

Answer 44

*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

Question 45

sucralfate

Answer 45

*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