Download 11 Mechanism of HCL Secretion In a parietal cell There is a

Mechanism of HCL Secretion
In a parietal cell
There is a hydrogen-potassium ATPase pump (which is on the right side on the
figure above), which lies on the apical or luminal membrane.
- The hydrogen ions that go into the lumen are our acid.
The hydrogen ions are produced by metabolism.
- Cellular metabolism with carbon dioxide reacting with water. Producing
bicarbonate and hydrogen ion.
- Water can also be broken down into its ions. Splitting water to get H+ and
OH-.
The bicarbonate ions that are left behind will affect the pH inside the parietal cell.
Thus they are moved back through the basolateral membrane (on the left side which
is into the blood plasma).
- It is exchanged for the chloride ion
- The movement of the bicarbonate into the plasma makes the blood more
alkaline and it is called the alkaline tide.
- That is why after a meal when you are producing more acid, the blood is more
basic.
- The urine will also be more alkaline (filtering plasma).
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The chloride ion that was exchanged for the bicarbonate will move across the
luminal membrane into the lumen of the gut.
- When mixed with hydrogen ions, it will create hydrochloric acid.
How the parasympathetic system stimulates stomach secretions:
The vagal nerve that innervates the stomach controls the secretions.
- When the vagal nerve is stimulated it releases acetylcholine.
The Ach acts on the muscarinic (M3) receptors and this:
- Releases calcium from the intracellular stores
- Allows calcium to enter from the extracellular locations too.
This combines to give us an increase in the calcium concentration within the cell.
The calcium can then bind to calmodulin to give us a complex.
This complex then binds and stimulates the hydrogen-potassium ATPase pump and
increases its activity.
Enterochromaffin-like cells (ECL)
When these are stimulated they release histamine into the lamina propria.
- They do not secrete it into the blood or lumen. The histamine is released
locally.
The histamine then acts on a H2 receptor. This H2 receptor is bound to adenyl
cyclase.
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The activation of adenyl cyclase then causes ATP to be broken down to cAMP.
The cAMP can go 2 pathways:
1. Broken down by phosphodiesterase to form AMP.
2. cAMP can bind with protein kinase A (PKA)
This cAMP-PKA complex will then stimulate the hydrogen-potassium ATPase
pump.
Caffeine inhibits
phosphodiesterase. That
means less cAMP will be
broken down into AMP.
-
More cAMP is available
to bind with PKA and
thus more acid can
enter the stomach.
Thus to summarise: to
stimulate acid secretion we
have the parasympathetic
nerous system stimulating the
M3 receptors via Ach.
Also we have histamine acting on the H2 receptors.
- They both go through different second messenger systems to stimulate the HK pump to increase acid
In the antrum of the stomach:
- The G cells secrete gastrin
- Via an endocrine mechanism, the gastrin will go to the fundus or boady of the
stomach and stimulate the CCK2 receptors on the Parietal cell.
- It works through the second messenger of calcium. However this process
does not directly stimulate the pump. It has a trophic effect on the parietal cell.
- The trophic effect: stimulates the size and number of the parietal cells.
Thus, gastrin does not really directly stimulate acid secretion via the pump (it has a
little effect). It indirectly does it by increasing the number and size of parietal
cells.
- Indirectly it also stimulates the ECL cells to secrete more histamine. Thus
increasing cAMP activity and proton pump activity.
Inhibition of Acid Secretion
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You have somatostatin released form the D cells of the antrum
This endocrine secretion acts on the receptors on the parietal cell to inhibit
acid secretion.
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The Interaction Between Parietal and ECF Cells
Histamine acts via paracrine signalling: histamine from ECF acts on the local parietal
cells.
Direct and Indirect pathways for HCL Secretion
1. IN the direct pathway, Ach, gastrin and histamine stimulate the parietal
cells, triggering the secretion of H+ into the lumen
2. In the indirect pathway, Ach and gastrin also stimulate the ECL, resulting in
the secretion of histamine. This histamine then acts on the parietal cell.
The green pathway is the direct pathway, while the indirect pathway is under it.
This above diagram is only in the body or fundus because there is only an acid
secreting oxyntic mucosa at those 2 regions.
Blockers:
If someone has acid reflux and you want to decrease its levels
- Ach – blocked by Atropine
- H2 receptor – blocked by Cimetidine / Ranitidine
- H+ Pump – blocked by Omeprazole (blocks both the pathways)
To stimulate acid secretion:
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Caffeine – inhibits cAMP breakdown.
Pentagastrin – synthetic form of gastrin (stimulates CCK2 receptors on both
ECL and parietal cells)
Gastrin on parietal cells – tropic effect
Gastrin on ECL cells – more histamine released
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Gastric Secretions – Parietal Cell histology
We normally have a basal
level of stomach acid
secretion
It is in the resting state when
we are sleeping at night.
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They’re re a lot of
mitochondria in the
resting state parietal
cell. This is because
producing acid is quite
the energy consuming
process.
There are banana shaped structures called tubulovesicles that are little
cleaved off section of apical or luminal membrane.
They contain proton pumps.
When the parietal cell is active:
- The tubulovesicles will merge and increase the surface area on the apical
membrane. The fusion of these vesicles forms canaliculi
- The result is not only a greater surface are abut more proton pumps as well.
The cell on the surface of the
stomach (Gastric mucous cells
(Goblet cells)) will be producing
mucous that protects the cells
from the acid (pH of 2).
- The mucous layer acts as
a diffusion barrier for pH
The Goblet cells also produce
bicarbonate, that helps to
neutralise the acid.
- Between and through the
cells, they are
impermeable to HCl.
Other Gastric Secretions
The chief cells release pepsinogen. The pepsinogen is cleaned to form pepsin when
in the presence of HCl (which is released from the parietal cells).
- Pepsin under autocatalysis can produce more pepsinogen, but stimulating
further cleaving of pepsinogen.
Pepsin is an endopeptidase, and thus can break down a protein chain of amino acids
into smaller peptide fragments
- It can cleave the middle of peptide chain.
- HOWEVER it cannot cleave amino acids from the end.
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