40 Gastric physiology

Question 1

Gastric secretions: 2L/day , including:
A. HCl
B. Mucus
C. Pepsin
D. Intrinsic factor

Answer 1

All of the above

Question 2

3 functions of HCl

Answer 2

1. Dissolve food particles
2. Convert inactive pepsinogen to active pepsin
3. Bacteriostatic to kill germs

Question 3

2 functions of mucus

Answer 3

1. Protective coating and lubricant for gastric mucosa

2. Maintain pH of gastric mucosa near neutrality i.e Gastric mucosal barrier

Question 4

2 functions of pepsin

Answer 4

1. Digest protein

2. Cleave pepsinogen to pepsin as positive feedback mechanism

Question 5

2 functions of intrinsic factor (essential component of gastric juice!)

Answer 5

1. Bind to absorb vitamin B12 in distal ileum

If not will cause malabsorption of fat (no fat soluble vit A,D,E,K) (K is for blood clotting)

2. Resection of distal ileum requires injection or oral B12 with IF supplement

Question 6

2 endogenous substances of the Gastric mucosal barrier?

Answer 6

HCl, pepsin

Question 7

Name 3 protections of the gastric lining

Answer 7

1. Restitution: rapid replacement of damaged cells by mucous neck cells (stem cells)
2. Mucous coating
3. Bicarbonate buffering (provide pH gradient)

Question 8

How is the pH gradient built in order to prevent ulcers?

Answer 8

H+ can diffuse directly to the lumen while HCO3- are mixed with the high viscosity mucus layer, causing a HCO3- buffering.

Question 9

5 structures you need to know about the stomach.

Answer 9

1. Lower esophageal sphincter (LES)
2. Fundus
3. Body
4. Antrum
5. Pyloric sphincter

Question 10

Functional anatomy: Which 2 kinds of gland mucosa are present in the stomach? Which is the majority ?

Answer 10

Oxyntic gland mucosa (proximal 80%)

Pyloric gland mucosa (distal 20%)

Question 11

In the oxyntic gland mucosa (acid secreting area), what cells secreted what kind of substances?

Answer 11

1. Parietal cells = oxyntic cells (HCl, intrinsic factor)
2. ECL (histamine)
3. D-cells (somatostatin that inhibits gastrin release from antral G cells)

Question 12

In the pyloric gland mucosa (gastrin-secreting area), what cells secreted what kind of substances?

Answer 12

1. Endocrine G-cells (gastrin)

2. Endocrine D cells (somatostatin to inhibit gastrin release in paracrine manner)

Question 13

What do surface epithelial cells secrete?

Answer 13

Mucus and HCO3-

Question 14

What do mucous neck cells secrete/ contain?

Answer 14

soluble mucous

stem cells

Question 15

What do parietal cells secrete?

Answer 15

HCl

IF

Question 16

Main function of peptic chief cells?

Answer 16

Secreting pepsinogen (precursor of pepsin)

Question 17

What are the 2 substances secreted by endocrine cells in a paracrine fashion?

Answer 17

1. Histamine (by ECF cells)
2. Somatostatin (by D cells)

Histamine diffuses to the parietal cells to regulate HCl and IF secretion

Question 18

Parietal cells
A. Require ATP for the process of secreting HCl with numerous mitochondria within the cells

B. Utilise H+/K+ ATPase to actively pump H+ at the expense of ATP (primary active transporter)

C. Undergo morphological change: invagination of apical membrane with numerous microvilli upon stimulation for increasing apical H+/K+ ATPase expression to drive active transport of H+

Answer 18

All

Question 19

In case of vomiting, which 2 ions are lost and what problems will arise?

Answer 19

chronic vomitting > hypokalemia: loss of K+ & metabolic alkalosis: loss of H+

Question 20

What ion pumps are present in the luminal cell

Answer 20

H+/K+ ATPase pump 1 H+ out and 1 K+ in the cell (luminal K+ is thus recycled)

Question 21

In blood, carbonic anhydrase is present to facilitate CO2 + OH- to become HCO3- in blood.
________ exchanger allow CL- goes to the lumen and create alkaline tide in gastric venous blood during acid secretion

Answer 21

Cl-/HCO3- exchanger

Question 22

Relationship of ECL cells and parietal cells: ECF cells synthesize ______ to mediate acid secretion of parietal cells in a ______ fashion.

Answer 22

Histamine; paracrine

Question 23

Relationship of endocrine D cells and parietal cells: D cells synthesize ______ to inhibit acid secretion of parietal cells in a ______ fashion.

Answer 23

Somatostatin; paracrine

Question 24

Relationship of antral G cells and parietal cells: G cells release ________ to ______ acid secretion.

Answer 24

Gastrin; stimulate

Question 25

Relationship of Prostaglandins from mucosal cells and parietal cells:Prostaglandins from mucosal cells ______ acid secretion of parietal cells in a ______ fashion.

Answer 25

inhibit; paracrine

Question 26

Relationship of Acetylcholine from nerve cells and parietal cells: Acetylcholine from nerve cells _______ acid secretion of parietal cells in a ______ fashion.

Answer 26

stimulates; neurocrine

Question 27

3 basic stimulants for acid secretion and their sites of action are:

Answer 27

Histamine, Gastrin and Ach. Histamine: H2 receptors on ECL cell Gastrin: CCK-B on antral G cells Ach: M3 muscarinic receptor on ECL cell

Question 28

Drugs to inhibit Ach is:

Answer 28

Atropine

Question 29

Drugs to inhibit histamine is:

Answer 29

Cimetidine (H2 blocker)

Question 30

Drug to inhibit gastrin is:

Answer 30

Proglumide

Question 31

Neurocrine ENS cell: M3 receptor; Paracrine ECL cell: H2 receptor; Endocrine G cell: CCK-B While H2 receptors stimulate Gs protein + Adenylate cyclase > cAMP > protein kinase > increase in H+ ; CCK-B and M3 receptor increases Ca2+ and therefore increase PK, then H+. The final pathway is :

Answer 31

stimulate H+/K+ ATPase

Question 32

Why is it more potent to stop the final pathway to stop acid secretion? What kind of drugs are used?

Answer 32

Irreversible binding of H+/K+ ATPase inhibitor/Proton pump inhibitor (PPI) (omeprazole).

Question 33

What are the 3 phases of gastric secretion?

Answer 33

1. Cephalic phase 2. Gastric phase 3. Intestinal phase 1. Cephalic phase ○ Neural regulation only (no acid secretion when vagus nerve is cut) ○ 30% of acid response a. Ach-mediated pathway on parietal cell (predominantly) b. GRP-mediated pathway on G-cell 2. Gastric phase ○ Neural and hormonal regulation ○ 60% of acid response a. Neural: long (?) and short reflexes (Ach acts on M3 receptor of parietal cells to secrete acid) b. Hormonal: at antrum, AA and peptides sensed by chemoreceptor on G cell cause gastrin release 3. Intestinal phase ○ Hormonal regulation (mainly inhibitory) 10% of acid response

Question 34

What cells are responsible for inhibiting acid secretion? (gastrin release too)

Answer 34

1. Secretin by S cell, responding to acid 2. Somatostatin by D cell, responding to acid 3. GIP by K and L cells, responding to glucose