Gastric Secretion Flashcards
What type of gland area is the body of the stomach?
Oxyntic Gland Area
Four cells in the oxyntic gland area?
1) mucous cells
2) chief cells
3) ECL cells (enterochromaffin-like)
4) Parietal cells
What do chief cell secrete?
Pepsinogen
What do ECL cells secrete?
Histamine
What do parietal cells secrete?
HCl (hydrochloric acid) and Intrinsic factors
What type of gland area is the lower part of the stomach called?
The pyloric gland area
Three cells in the pyloric gland area?
1) Mucous cells
2) G cells
3) D cells
What do G cells in the pyloric gland area secrete?
Gastrin
What do D cells in the pyloric gland area secrete?
Somatostatin
What do the surface mucosa cells of the pyloric region secrete?
A *thick *protective *alkaline-rich Mucus.
This makes the gastric mucosal barrier.
What stimulates the gastric mucosa cells?
1) mechanical irritation
2) chemical irritation
3) parasympathetic inputs
Three things that can damage the gastric mucosal barrier?
1) bacterial infections
2) viral infections
3) certain drugs (e.g. aspirin)
What is the concentration, volume and pH of stomach acid produced daily?
Conc = 150-160mM Vol = 1-2L pH = 0.8-1
Explain the process of activating the proton pump (H+/K+-ATPase).
- When proton pumps are at rest, they remains in cytoplasmic vesicles.
- When stimulated, the proton pump vesicles membrane fuse with the parietal cell membrane.
- This increase SA of proton pump so more acid secretion.
Three chemicals that influence stomach acid secretion are…
1) histamine
2) acetylcholine
3) gastrin
How does acetylcholine affect GA secretion?
The enteric neurons release acetylcholine. This directly stimulates the parietal cell for a greater GA secretion!
-also stimulates ECL to release H2 which increases GA secretion
How does histamine affect GA secretion?
1) ECL cells secrete histamine
2) Histamine stimulates the parietal cells
3) stimulates increase in GA secretion.
4) histamine has a paracrine activity in which it stimulates nearby cells to be activated.
How does gastrin influence GA secretion?
1) secreted by G cells
2) stimulates ECL cells to release histamine
3) this stimulates parietal cells to secrete GA.
Which of the three factors affecting GA secretion directly stimulates parietal cell proliferation?
Gastrin
What does cell proliferation mean?
Rapid increase in the number of cells by replication.
What are the positive regulators of GA secretion?
Acetylcholine
Histamine
Gastrin
(This means that when you increase these chemicals, the rate/amount of acid secretion will also increase)
Give an example of a negative regulator of GA secretion.
Somatostatin
How does somatostatin work in reducing GA secretion?
1) when secreted by D cells, it directly inhibits parietal cells from secreting acids.
2) it also inhibits gastrin and histamine secretion
Gastrin has an endocrine action. What does this mean?
It means it gets distributed in the blood before binding to the target cells (ECL cells)
What receptor does acetylcholine bind to on the parietal cell?
Muscarinic (M3) receptor
What receptor does gastrin bind to on the parietal cell?
Cholecystokinin B (CKKB/CCK2)
What receptor does histamine bind to on the parietal cell?
Histamine H2
What is the most powerful stimulus for HCl secretion?
Histamine
Acetylcholine, gastrin and histamine all act through the G-coupled receptor. What chemicals/products are increased by the presence of these 3?
Ach and gastrin = diacylglycerol and Ca2+
Histamine = cyclic Amp (cAMP)
What happens when we have too much stomach acid?
1) stimulates somatostatin releasing cells (aka D cells) to release somatostatin
2) somatostatin is released
3) somatostatin directly affects parietal cells and inhibits gastrin and histamine secretion.
Describe the cephalic phase.
1) the phase stimulus (sight/smell/thought of food)
2) stimulates the parasympathetic preganglionic neurons
3) this activates the enteric neurons
4) which release acetylcholine
5) which binds to the muscarinic (M3) receptor
6) this stimulates HCl release.
What happens during the gastric phase?
1) when food is in the stomach, it does 4 things:
2) the peptides stimulate G cells to release gastrin
3) the food increases stomach pH which prevents D-cell activity (somatostatin won’t be secreted as pH isn’t too acidic)
4) it stimulates the mechanoreceptor neural reflex.
5) stimulates ECL cells to release histamine
Explain the mechanoreceptor neural reflex in the gastric phase
1) food in stomach causes distension on stomach muscles
2) this activates enteric neurons
3) hence stimulating acetylcholine (Ach) secretion.
What happens during the intestinal phase?
1) chyme (food surrounded by acid and gastric juices) enters duodenum
2) pH/D-cells feedback mechanism prevents chyme acidity
3) less food in stomach causes pH to fall back down stimulating D cell activity
4) duodenal stimulation of hormones
What hormones does the duodenum stimulate?
Enterogastrones: a) cck (cholecystokinin) B) secretin C) GIP d) GLP-1
These all inhibit G-cells, ECL cells and Parietal cells
Effect of distension in intestinal phase on acetylcholine secretion?
- less distension in stomach
- mechanoreceptor neural reflex doesn’t take place
- enteric neurons aren’t activated
- Ach isn’t released hence less HCl released
Explain the feedback mechanism in acid level in stomach
1) high acid levels stimulate D cells
2) these release somatostatin
3) this reduces gastrin and histamine release
4) less HCl secreted
5) too low HCl
6) D-cells stop releasing somatostatin
7) histamine and Gastrin released
8) more HCl released
Mechanism of HCl secretion…
1) CO2 diffuses into parietal cells from plasma
2) CO2 is hydrated to carbonic acid by carbonic anhydrase
3) carbonic acid (H2CO3) dissociates to H+ and HCO3-
4) H+/K+ ATPase (proton pump) actively transports H+ out of parietal cell and K+ into parietal cell
5) Na+ is actively reabsorbed
6) K+ moves back out to be recycled in the gastric lumen, hence elevating K+ of gastric juices
7) Cl- leaves cell passively via Cl- channel to form HCl with H+ in the lumen.
Conc of HCl, KCl and NaCl in the gastric juices…
HCl = 160mM KCl = 15mM NaCl = small amount
What is the role of the K+/Na+ ATPase transporter?
Transport Na+ out and K+ into cell.
What is used to maintain cell pH?
The transport of HCO3- out of and Cl- into the cell by a common transport protein.
What is the effect of the muscarinic (M3) and CCKB receptors of parietal cells?
Increase Ca2+ and IP3 concentrations
What is the effect of histamine receptors on parietal cells?
Increase cAMP
What is the effect of somatostatin receptors (SSTR1) on parietal cells?
Reduce cAMP
Role of prostaglandin in acid regulation…
1) PGE2 binds to prostanoid receptors (EP3)
2) this reduces cAMP (required for signal transduction)
3) this inhibits acid secretion and stimulates mucus and bicarbonate secretion.
5 roles of PGE2
1) increase mucus secretion
2) increase cell regeneration
3) reduce HCl secretion
4) increase HCO3- secretion
5) increase blood flow
How is the mucous membrane protected from HCl?
1) surface epithelial cells secrete HCO3- which is stimulated by Ach, HCl and PGs
2) HCO3- accumulates near cell surface
3) mucous protect membrane by trapping HCO3- rich fluid near apical border of epithelia.
4) this neutralises acid near the surface avoiding corrosion
What causes mucous cells to secrete mucin?
Vagal stimulation and irritation
What is mucin?
A glycoprotein part of the mucosal barrier
Why does mucin need to be constantly produced?
Because pepsin (an enzyme that breaks down proteins), cleaves/breaks down mucin
What inhibits HCO3- secretion?
Adrenergic input (prominent in stress)
How is H+ diffusion out of the lumen inhibited?
Tight junctions in the cell membrane makes the membrane impermeable to H+ ion diffusion.
