Gastric Secretion

Question 1

What are the important parts of the stomach?

Answer 1

Fundus
Body
Antrum
Cellular composition (mucous neck cells, chief cells and parietal cells)

Question 2

What is the function of the fundus?

Answer 2

Storage: walls are thin and stretchy to allow for expansion to balance pressure

Question 3

What is the function of the body of the stomach?

Answer 3

Storage

Release of mucus, HCl, pepsinogen and intrinsic factor

Question 4

What is the function of the antrum?

Answer 4

Mixing/grinding

Release of gastrin (produced by G cells and stimulates HCl release)

Question 5

What is the function of mucous neck cells?

Answer 5

Mucus secreting and precursors for mature surface mucous cells

Question 6

What is the function of chief cells?

Answer 6

Secretes pepsinogen (to digest proteins) and gastric lipase (to digest fat)

Question 7

What is the function of parietal cells?

Answer 7

Releases HCl and intrinsic factor

Question 8

What are the effects of the release of HCl into the stomach from parietal cells?

Answer 8

Releases of pepsin (digest protein)
HCl denatures proteins by breaking disulphide and hydrogen bonds to allow pepsin to get more peptide bonds
HCl kills bacteria and other ingested organisms
Inactivates salivary amylase,(stops carb digestion that began in the mouth)

Question 9

Other than secretion, what is the function of parietal cells?

Answer 9

Specialised epithelial cells with tight junctions important to prevent gastric acid from diffusing though and damaging outside environment

Question 10

How is HCl formed in parietal cells?

Answer 10

1. CO2 diffuses across membrane from the blood and combine with water in the cytoplasm
2. The conversion of CO2 and H2O into unstable carbonic acid is aided by carbonic anhydrase
3. Acid immediately dissociates
4. The H+ ions are actively pumped out of cell (with ATP) whilst K ions are pumped in – proton pump H-K-ATPase
5. Bicarbonate diffuses out of the basolateral membrane into the blood, in exchange for Cl, making the blood that leaves the stomach less acidic
6. Cl- immediately exits the cell via Cl channel in apical membrane
7. Water is drawn from the blood and into the stomach lumen as HCl is formed in stomach lumen

Question 11

What four hormones that stimulate generation of ATP in the stomach?

Answer 11

Gastrin
Histamine
Prostglandin
Acetylcholine

Question 12

How does Histamine stimulate acid production?

Answer 12

It is a paracrine released from enterochromaffin (ECL) cells and its adhesion to molecule on the basolateral membranes, stimulates protein Gs to activate andenylyl cyclase, which converts ATP –> cAMP

cAMP stimulates protein kinase to allow the H/K-ATPase pump

Question 13

What is the key protein for acid secretion in parietal cells?

Answer 13

H/K-ATPase (proton pump) - expressed at the apical membrane which uses energy derived from ATP hydrolysis to pump H+ ions into the lumen in exchange for potassium ions

Question 14

Name a regulatory molecule that inhibits acid secretion in parietal cells

Answer 14

Somatostatin

Question 15

How does gastrin activate H/K-ATPase?

Answer 15

Binding releases Ca to act on protein kinase

Also stimulates ECL to release Histamine

Question 16

How does Prostaglandins activate H/K-ATPase?

Answer 16

Stimulate Gi protein which is positively coupled to adenylyl cyclase to convert ATP to cAMP

Question 17

How does Acetylcholine activate H/K-ATPase?

Answer 17

Acts on muscarinic cholinergic receptors and binding increases levels of Ca which activates protein kinase C

ACh also stimulates ECL cells to release histamine

Question 18

What three mechanisms control gastric acid secretion?

Answer 18

Neurocrine (vagus/local reflexes)
Endocrine (gastrin)
Paracrine (histamine)

Question 19

How does the parasympathetic system effect gastric secretion?

Answer 19

Sight, smell, taste –> triggers vagus nerve which stimulates release of acetyl choline to act on parietal cells

Also innervates G cells which release gastrin which stimulates HCl release and histamine from ECL cells

Question 20

What are the three phases of mechanisms involved in inhibiting gastric acid secretion?

Answer 20

Cephalic phase
Gastric phase
Intestinal phase

Question 21

What occurs in the cephalic phase during inhibition of gastric acid secretion?

Answer 21

Stopping eating –> decrease in vagal activity

Question 22

What occurs in the Gastric phase during inhibition of gastric acid secretion?

Answer 22

Decrease in pH (due to increase in HCl) –> decrease in gastrin (less release of HCl)

Question 23

What occurs during the Intestinal phase of inhibition of gastric acid secretion?

Answer 23

Acid in duodenum –> Secretin release AND enterogastric (splanchnic) reflex –> Decrease gastrin secretion and gastrin stimulation of parietal cells

Question 24

What is GIP?

Answer 24

Gastric inhibitory polypeptide - inhibits gastric acid secretion

Question 25

What is the effect of the presence of Fat/CHO in the duodenum?

Answer 25

GIP release --> decrease in gastrin secretion and parietal HCl secretion (as no more need for it if food now exited the stomach)

Question 26

What is the role of secretin?

Answer 26

Stimulates secretion of bicarbonate from pancreas to neutralise the acid in the duodenum, so gastrin is inhibited to stop more acid being released

Question 27

What are enterogastrones and give 3 examples?

Answer 27

Hormones released from gland cell is duodenal mucosa Secretin Cholecystokinin (CCK) GIP

Question 28

What stimulates release on enterogastrones?

Answer 28

Acid, hypertonic solutions, fatty acids or monoglycerides in the duodenum They act to prevent further build up in duodenum

Question 29

What are the mechanisms of enterogastrones?

Answer 29

Inhibit gastric acid secretion | Reduce gastric emptying (inhibit motility/contract pyloric sphincter)

Question 30

What is the inactive precursor of pepsinogen?

Answer 30

Zymogen

Question 31

Why is pepsinogen stored as zymogen?

Answer 31

To prevent cellular digestion and is inactive at neutral pH

Question 32

What cells secrete pepsinogen?

Answer 32

Chief cells

Question 33

What is the role of pepsinogen?

Answer 33

At low pHs (< 3 when acid present), pepsinogen converted to pepsin through acid hydrolysis - i.e. when food is present, and acid released to break down food, pepsin is required to digest proteins

Question 34

What cells of the stomach produce gastric mucus?

Answer 34

Epithelial cells and mucus neck cells

Question 35

What is the function of gastric mucus?

Answer 35

``` Cytoprotective role: Protect mucosal surface from mechanical injury Neutral pH (HCO3) --> protects against gastric acid corrosion and pepsin digestion ```

Question 36

What is the function of intrinsic factors?

Answer 36

Required to form a complex with vitamin B12 to allow Vitamins B12 to be absorbed by ileum

Question 37

What can deficiency in Vitamins B12 cause?

Answer 37

Pernicious anaemia