Physiology and Pharmacology of Gastric Motility and Secretion

Question 1

What is stomach relaxation driven by?

Answer 1

vagus nerve

Question 2

What is the starting point for digestion of proteins?

Answer 2

HCl and pepsin

Question 3

What is produced by the stomach?

Answer 3

chyme

Question 4

What are the rugae?

Answer 4

folds in the empty stomach

Question 5

What is the fundus?

Answer 5

top of stomach, gas pocket, usually no food

Question 6

What is the antrum?

Answer 6

next to duodenum - thick sm. muscle for contraction

Question 7

How is food mixed in the stomach?

Answer 7

peristalic wave forces chyme down and back against pyloric sphincter which causes retropulsion

Question 8

What size of food does the pyloric sphincter let through?

Answer 8

2mm or less

Question 9

What governs the strength of the antral wave?

Answer 9

gastric factors and duodenal factors

Question 10

What are the gastric factors mediating the antral wave?

Answer 10

rate of emptying is proportional to volume of chyme in stomach
distension increases motility due to stretch of smooth muscle, stimulation of intrinsic nerve plexus and increased vagal nerve activity and gastrin increase
consistency of chyme

Question 11

What are the duodenal factors mediating the antral wave?

Answer 11

must be ready to recieve chyme and can delay emptying

Question 12

How does the duodenum delay emptying of the stomach?

Answer 12

neuronal response - enterogastric reflex decreases antral peristalic wave from intrinsic nerve plexuses and ANS
hormonal response - release of secretin and CCK

Question 13

What are the stimuli that drive the neuronal and hormonal responses of the duodenum?

Answer 13

fat - particularly potent as time required for digestion
acid - time needed for neutralisation by HCO3
hypertonicity - products of carbohydrate/ protein digestion are osmotically active and draw water into the sm. intestine
distension

Question 14

Where do secretions from the gastric glands come from?

Answer 14

Pyloric Gland Area

Oxyntic Mucosa

Question 15

What is produced by the oxyntic mucosa?

Answer 15

enterochromaffin cells - histamine - paracrine
chief cells - pepsinogen
parietal cell - HCl, Intrinsic factor

Question 16

What is produced by the pyloric gland area?

Answer 16

D cell - somatostatin - endocrine

G cell - gastrin - endocrine

Question 17

What is the function of HCl?

Answer 17

activates pepsinogen -> pepsin
denatures protein
kills most micro-organisms ingested

Question 18

What is the function of pepsinogen?

Answer 18

inactive precursor of peptidase - pepsin

pepsin is autocatalytic once formed

Question 19

What is the function of Intrinsic Factor?

Answer 19

binds vitB12 - allowing absorption in the terminal ileum - essential as only found in stomach

Question 20

What is the function of histamine?

Answer 20

stimulates HCl secretion

Question 21

What is the function of mucus?

Answer 21

protects stomach wall

Question 22

What is the function of gastrin?

Answer 22

stimulates HCl secretions

Question 23

What is the function somatostatin?

Answer 23

inhibits HCl secretion

Question 24

What are the processes involved with secretion of HCl?

Answer 24

Conversion of CO2 and H20 to HCO3 + H
HCO3 exiting the cell and bringing Cl into the cell
H being extruded into the cannaliculus
Cl being extruded into the cannaliculus

Question 25

What converts CO2 and H20 to H2CO3?

Answer 25

carbonic anhydrase

Question 26

What takes HCO3 out of the cell?

Answer 26

HCO3/Cl antiporter

Question 27

How is H taken into the cannaliculus?

Answer 27

via H-K ATPase

Question 28

Which cell produces HCl?

Answer 28

The parietal cell

Question 29

How is H+ increased by the parasympathetic nervous system?

Answer 29

ACh stimulates M3 on parietal cells and M1 on ECL cells Gastrin activates CCK2Rs on parietal and ECL cells Hitamine generated from M1 and CCK activates H2R on parietal

Question 30

What inhibits the production of HCl?

Answer 30

somatostatin by inhibiting gastrin release | PGE2 inhibits all H2, M3 and CCK2 Receptors

Question 31

Where are proton pumps found between meals?

Answer 31

tubulovesicles

Question 32

What happens to the proton pumps when stimulated?

Answer 32

move to the apical membrane in extended microvilli

Question 33

What are the 3 phases of Gastric Secretion?

Answer 33

Cephalic Gastric Intestinal

Question 34

What happens in the cephalic stage?

Answer 34

Vagal activation of enteric neurons ACh stimulates D cell which stops release of somatostatin and increases Gastrin release ACh increases Gastrin Releasing Peptide and increases G cell activity and gastrin Ach stimulates the parietal cell to produce HCl Ach stimulates the ECL cell to produce histamine which stimulates the parietal cell to produce HCl

Question 35

What happens in the gastric stage?

Answer 35

distension stimulates mechanoreceptors which stimulate G cell and increase gastrin and HCl Protein digestion products also stimulate the release of gastrin

Question 36

What happens in the intestinal stage?

Answer 36

the same factors that reduce gastric motility reduce gastric secretion as the stomach empties the stimulus for secretion is less intense secretion of somatostatin resumes

Question 37

What are some of the drug classes that influence acid secretion?

Answer 37

Muscarinic R Antagonists H2R antagonists Proton-pump inhibitors NSAIDsn

Question 38

What is the effect of Muscarinic Antagonists? Give an example

Answer 38

decrease HCl | Pirenzipine

Question 39

What is the effect of H2R blockers? Give an example

Answer 39

decrease HCl | Ranitidine

Question 40

What is the effect of Proton-pump inhibitors? Give an example

Answer 40

decrease HCl | Omeprazole

Question 41

What is the effect of NSAIDs? Give an example

Answer 41

increase HCl - blocks only negative control of pathway | Aspirin

Question 42

What is the effect of NSAIDs? Give an example

Answer 42

increase HCl - blocks only negative control of pathway | Aspirin

Question 43

What is the function of prostaglandins in the mucosa of the stomach?

Answer 43

reduce acid secretion increase mucus and HCO3 secretion increase mucosal blood flow

Question 44

What may result from taking NSAIDs?

Answer 44

gastric ulceration and bleeding

Question 45

How might the effects of NSAIDs be counteracted?

Answer 45

taking PGE1 analogue such as misprostol or COX2 selective inhibitors

Question 46

What does misoprostol do?

Answer 46

inhibits basal and food stimulated gastric acid formation | maintains secretion and mucus and HCO3

Question 47

What does Helicobactor pylori do?

Answer 47

burrows into the mucosal gel and secretes agents that cause persistent inflammation weakening the mucosal barrier

Question 48

When are drugs that reduce acid secretion used?

Answer 48

Gastric ulcer gastro-osophageal reflux acid hypersecretion

Question 49

What are some mechanisms of anti-secretory activity?

Answer 49

inhibition of the H-pump competitive antagonism of H2R competitive antagonism of M1,M3Rs antagonism of gastrin receptors CCK2R

Question 50

How do proton pump inhibitors work?

Answer 50

inhibit the active, membrane inserted form of H-K-ATPase

Question 51

How are proton pump inhibitors delivered to the stomach?

Answer 51

absorbed in GI tract and transported via systemic circulation to secretory cannaliculi

Question 52

How are proton pump inhibitors activated?

Answer 52

by accumulation they are converted to a sulfenamide

Question 53

How do proton pump inhibitors inhibit the pump?

Answer 53

covalent modification of sulphydryl groups on the pumps

Question 54

How often would you take a proton pump inhibitor?

Answer 54

once daily, more if there is a nocturnal acid break through