Lecture 28

Question 1

What are 4 components of gastric acid secretions?

Answer 1

1. acid
2. pepsin
3. intrinsic factor
4. mucus

Question 2

What is the function of acid?

Answer 2

It has a protective role against bacteria such as that on our food. It also denatures proteins as part of chemical degradation. This is also the optimum pH for many digestive enzymes. It also renders the fluid isosmotic (150 mM HCl - HCO3–neutralised part to protect the epithelial lining)

Question 3

What is the purpose of pepsin?

Answer 3

This breaks down proteins

Question 4

What is the purpose of intrinsic factor?

Answer 4

This is for the absorption of vitamin B12 for the formation of DNA and RBC

Question 5

What is the purpose of mucous?

Answer 5

This protects against the acid and mechanical forces - it makes the epithelium elastic

Question 6

What are the different parts of the stomach and what is secreted in each part?

• LES and cardia for the secretion of m______ and ______-
• the fundus and body of the stomach for the secretion of ______, ________ factor, m______, l_____, _____-, p______n
• antrum and pylorus for the secretion of m_______ and ______-

Answer 6

• LES and cardia for the secretion of mucus and HCO3-
• the fundus and body of the stomach for the secretion of H+, intrinsic factor, mucus, lipase, HCO3-, pepsinogen
• antrum and pylorus for the secretion of mucus and HCO3-

Question 7

Where is gastrin secreted from? Why is this location important?

Answer 7

It is released in the late part of the stomach to control the release of acid from the fundus

Question 8

Describe the structure of the stomach

Answer 8

There are invaginations in the lamina propria which are the gastric glands. The cells in here have different functions of gastric secretions

Question 9

Describe the functions of the different cells in the gastric glands

There are the _________ cells which produce _________ to protect against the ________. There are ________ cells which are close to the surface to make the epithelium _______ and so help with ________ forces and to protect against the ______. There are ________ cells which are further down the gland which secrete _______ and _______ factor. There are ________ cells further down which secrete ________ and then there are __________ like (ECL) cells which secrete _________ for the control of _______ ________ secretion

Answer 9

There are the surface cells which produce HCO3- to protect against the acid. There are mucus cells which are close to the surface to make the epithelium elastic and so help with mechanical forces and to protect against the acid. There are parietal cells which are further down the gland which secrete acid intrinsic factor. There are chief cells further down which secrete pepsinogen and then there are enterochromaffin like (ECL) cells which secrete histamine for the control of gastric acid secretion

Question 10

How many litres of gastric secretions do we produce each day? The composition of these secretions depend on what?

Answer 10

2-3 L

The composition depends on whether you are eating or fasting

Question 11

When we are not eating, how much gastric secretions do we produce per hour? What is the composition of this?

Answer 11

15 - 30 mL/h
This is secreted constantly whether you are eating or not. It is secreted by surface cells. This is an isosmotic solution with similar [Na+] to plasma but higher [HCO3-]. There is also mucus secreted

Question 12

Describe the volume and composition of gastric secretions when we are eating. How much is it and what is the composition?

Answer 12

150 mL/h

• isosmotic (150mM) solution of HCl produced by parietal cells
• a bit of HCO3- to protect the surface cells
• pepsinogen secreted by the chief cells
• intrinsic factor secreted by the parietal cells
• mucus

Question 12

Describe the volume and composition of gastric secretions when we are eating. How much is it and what is the composition?

Answer 12

150 mL/h

• isosmotic (150mM) solution of HCl produced by parietal cells
• a bit of HCO3- to protect the surface cells
• pepsinogen secreted by the chief cells
• intrinsic factor secreted by the parietal cells
• mucus

Question 13

What is the final osmolarity of the gastric secretion with the 150mM of HCl and the HCO3- that is secreted to help protect the surface cells?

Answer 13

around 200mOsmol/L

Question 14

What does the final composition of gastric secretion depend on?

Answer 14

the rate of secretion

Question 15

Which ion concentration increases the most when there is an increase in the rate of secretion?

Answer 15

H+

Question 16

Gastric secretions

A. consist of bile acids.
B. between meals have a rate of 3 mL/min.
C. of surface epithelium are mucus and bicarbonate.
D. of chief cells contain intrinsic factor.
E. increase upon stimulation by a factor of 100

Answer 16

C. of surface epithelium are mucus and bicarbonate.

Question 17

What is associated with the stimulation of acid secretion?

Answer 17

A number of structural changes in the parietal cells

Question 18

Describe a non-secreting parietal cell. When are they not secreting?

Answer 18

They are not secreting when you are fasting.
The non-secreting cell have small intracellular canaliculi and short stubby microvilli at the apical pole. There is also an extensive tubulovesicular system

Question 19

What is the tubulovesicular system in a non-secreting parietal cell?

Answer 19

This has the holding components for the acid secretion, but they are quiescent

Question 20

Describe a secreting parietal cell

Answer 20

The tubulovesicular system disappears and there is development of extensive intracellular canaliculi. There is also the appearance of large apical microvilli which increases the surface area of the apical membrane by 50-100 fold

Question 21

What is the purpose of the structural changes in the parietal cell?

Answer 21

There is the insertion of H+/K+ ATPase which is responsible for acid secretion.

Question 22

How does the H+/K+ ATPase work in the parietal cell?

Answer 22

It is a primary active transporter which utilises ATP to actively transport H+ out of the cell in exchange for the K+ into the cell. 80% of the protein int he tubulovesicular membrane is the H+/K+ ATPase

Question 23

Where is H+/K+ ATPase located in a non-secreting parietal cell?

Answer 23

It is sitting in vesicles underneath the membrane waiting to be released to be activated

Question 24

Where is the H+/K+ ATPase sitting in a secreting parietal cell? What else is in that apical membrane?

Answer 24

Once activated, they are incorporated into the membrane | There are also K+ and Cl- channels incorporated into the membrane acting as a driving force

Question 25

Describe the events at the apical membrane of a secreting parietal cell

Answer 25

- K+ and Cl- diffuse down their electrochemical gradients into the lumen via channels - K+ is recycled back across the apical membrane via H+, K+- ATPase - secretion of HCl - water follows passively

Question 26

The secretion of hydrochloric acid (HCl) A. is dependent on an apical (luminal) K+ gradient. B. requires an apical bicarbonate gradient. C. requires an apical Na+ gradient. D. requires the change of the parietal cells from large intracellular canaliculi to an extensive tubulovesicular system. E. requires a secondary active apical transport system.

Answer 26

A. is dependent on an apical (luminal) K+ gradient.

Question 27

What are four transporters in the basolateral membrane? What is the purpose of each of them?

Answer 27

- Na+/K+ ATPase: this maintains the K+ in the cell above the equilibrium - K+ channel: recycles K+ and generates the membrane potentials - Na+/H+ and Cl/HCO3- exchanger: pH homeostasis and maintenance of Cl- above the equilibrium

Question 28

Where does the H+ come from to be secreted out of the stimulated parietal cell?

Answer 28

CO2 is combined with H2O by CA and this forms H2CO3. This is then broken down to HCO3- and H+ which can then be pumped out of the cell via H+/K+ ATPase

Question 29

Where does the HCO3- produced in the parietal cell go?

Answer 29

This leaves basolaterally via the HCO3-/Cl- into the blood

Question 30

What is a drug that blocks the H+/K+ ATPase and when is this prescribed?

Answer 30

Omeprazole which is prescribed for gastric ulcers or reflux

Question 31

What transporter can be used as a backup for the maintenance of pH if shit hits the fan?

Answer 31

Na+/K+ ATPase

Question 32

Describe the role of the Cl-/HCO3- exchanger

Answer 32

- for each mole of H+ ion secreted an equivalent amount of base is produced - this is extruded across the basolateral membrane by the Cl-/HCO3- exchanger (alkaline tide after a meal) - this provides the Cl- ion that is secreted with H+

Question 33

Pepsins are also secreted. What are they, what are they secreted as and what do they do?

Answer 33

These are proteolytic enzymes which are secreted as an inactive precursor pepsinogen by the chief cells. Pepsinogen is converted to active pepsins by acidic pH and other pepsins.

Question 34

Mucus and HCO3- are also secreted. Explain the purpose of this

Answer 34

- mucus secreted by mucus neck cells in glands and surface cells - HCO3- rich solution secreted by surface cells - get a layer of alkaline mucus that protects the stomach from abrasion and acid pH

Question 35

How does the HCO3- help? Where does it come from?

Answer 35

This forms a layer above the surface cells which protects them from the acid It comes from the CA reaction and from the blood

Question 36

How does the osmolarity of the solutions change between the fasting and feeding state? - fasting: close to __________, high in ________ and ___________ coming entirely from __________ cells - feeding: first ________, low in _______, ______mM HCl, then ________-osmotic due to surface processes

Answer 36

- fasting: close to isosmotic, high in sodium and bicarbonate coming entirely from surface cells - feeding: first isosmotic, low in sodium, 150mM HCl, then hypo-osmotic due to surface processes