Gastric Acid Secretion: Regulation Flashcards
The Stomach and Contents of Normal Gastric Juice
what is secreted in the stomach?
what type of cells are also around the cardiac and pyloric area?
what is secreted in the antrum? describe the antrum - thickness? why?
chief cells secrete what?
parietal cells secrete what? essential for what?
what doe gastric juice contrain in fasting state?
The fundus and body have glands that secrete pepsinogen, mucus & acid.
Around the cardiac area there are also mucus-secreting cells and around the pyloric area there are mucus secreting cells.
The antrum is quite thick in terms of muscular structure and secreted mucus, pepsinogen and gastrin.
The body of the stomach contains chief cells secreting pepsinogen and also parietal cells release intrinsic factor, which is necessary for vitamin B12 absorption.
Gastric juice contains (in fasting state):
- Cations: Na+, K+, Mg2+, H+ (has a pH of around 3)
- Anions: Cl-, HPO42-, SO42-
- Pepsins
- Lipase
- Mucus
- Intrinsic factor
The gastric juice adds about 2.5L/day of to the intestinal contents
The Stomach
thickness of upper portion?
what does it secrete?
what kind of secretions are these?
what does the body have a lot of? (2 things) -> what are these linked to? to release what?
what increases acid secretion?
what secretes histamine? what kind of communication is this?
The upper portion of the stomach is thin-walled (fundus and body) and secretes mucus, HCl and pepsinogen -> these are exocrine secretions of the stomach.
The body has numerous epithelial cells with numerous tubular glands.
Wall of the glands is linked with parietal cells which release HCl and intrinsic factor.
Gastrin increases acid secretion, to do this it needs to bind to its receptor.
The enterochromaffin-like cells (ECL) secrete paracrine agents e.g. histamine.
How is Gastric Acid Made?
How is carbonic acid made? what happens to this?
Why is bicarbonate needed in venous blood from stomach? how does it get in?
How does Cl- and H+ enter the stomach?
what three things drive gastrin formation?
where do fundal glands secrete into?
CO2 diffuses in and reacts with water to produce carbonic acid, -> dissociates into a bicarbonate and proton. Bicarbonate exchanged for a Cl- in the blood, which decreases the acidity of venous blood from the stomach.
Excess Cl- diffuses into the stomach through chloride channels as the H+ is pumped into the stomach lumen via K+/H+ ATPase, this pumps H+ out into the lumen of the stomach.
The net effect is a net flow of H+//Cl- out of the parietal cell and into the lumen of the stomach.
There are three things driving this formation
1. Gastrin
2. Ach
3. Other mediators
Fundal glands secrete into the pits (pepsinogen is an inactive enzyme that needs to be activated to pepsin)
Gastric Secretions
what is the resting juice (not fasting or eating) compared to plasma?
why is a lot of mucus present?
what are lipases produced? what happens if no lipases produced?
why is instrinsic factor essential? what does it prevent?
why is HCL essential? ( 2 reasons)
The resting juice (when not fasting or eating) is similar to plasma but a little bit more alkaline due to higher HCO3-.
There is also mucus present which is thick and sticky, it is important in protecting the epithelial cells that line the stomach. They protect these cells from the H+.
Lipases break down TAGs fatty acids + glycerol. If you do not produce lipase= do not digest fats but there are other things which can mediate it, but you end up passing unpleasant sticky faeces.
Intrinsic factor prevents pernicious anaemia, through absorption of vitamin B12.
HCl kills bacteria, it is involved in the acid denaturation of digested food and activates pepsinogen -> pepsin (important in protein digestion).
HCl Secretion by Parietal Cells
How does HCL secretion change when we eat?
What are the 3 meal phases?
What 2 things regulate HCL secretion? what are these called collectively?
How is this done directly?
how is this done indirectly?
What turns off HCL secretion?
At meal times we increase HCl secretion.
There are 3 phases that are important in this
- Cephalic
- Gastric
- Intestinal phases
HCl secretion is regulated by neuronal pathways and duodenal hormones = called enterogastrones.
This is done:
- Directly
o By acting on parietal cells to increase acid secretion
- Indirectly
o By influencing the secretion of gastrin and histamine, this increases acid secretion.
So, all this is pushing HCl secretion, so what is turning it off?
Some of the enterogastrones (duodenal hormones are important in this, because we need to modulate release.
Gastric Acid Secretion: Regulation
What is the cephalic phase? what does it cause? What does this stimulate and from where? Where do these act on and what is the effect of this?
describe the activation and action of parasympathetic and enteric system
action of G cells
How is HCL release regulated? what is the effect of this?
What is the gastric phase? What stimulates neurones? what food will make further acid to be released? What system is stimulated? what is released and where does this stimulate?
effect of peptides acting as a buffer in our stomach
another effect of protein for acid release?
What will the increased acid secretion do? why is this useful?
Why is it bad if someone with GORD ate lots of protein?
What is the balance we want here?
what inhibits acid secretion? why? what is important for this control? (name 5 factors that lead to the inhibition of acid)
How does chyme affect the inhibition? (2 factors)
name the 3 different main systems that inhibt acid secretion and where they act on
how does the symoathetic system come into play?
Cephalic phase is when we start smelling, seeing (and tasting or chewing) some food, this will result in Ach release.
Ach stimulates histamine release from ECL cells and Ach acts directly on parietal cells to increase HCl secretion.
Cephalic phase
Cephalic phase (which has started from the higher centres that have responded to the senses) stimulates the parasympathetic neurones -> releases Ach acting on the parietal cells which then secrete HCl.
The stimulation of enteric nervous system (from parasympathetic) -> stimulates ECL cells to release histamine which act on parietal cells to secrete HCl.
Even the G-cells can be activated to release gastrin, which act on ECL cells release histamine which then itself stimulates parietal cells to release HCl.
Acid can be damaging, so we need a way to regulate HCl release. This done by HCl stimulating somatosatin released from D-cells.
Somatostatin inhibits ECL and G cells to stop hypersecretion of acid.
Gastric phase
Gastric phase
This is where you’ve ingested the food and there is distension of the stomach this stimulates neurones, if protein (peptide concentration goes up) also, then this stimulates acid release and acidity will increase (lowering of pH). This is important as we are increasing acidity here.
- Distension of the stomach stimulates enteric nervous system to release more Ach and stimulate HCl release from parietal cells (also it acts on ECL cells and on G-cells).
o So, distension has a big role to play in terms of the effects we get.
Importantly, peptides in our food act as a buffer of acid (decrease [H+]) to prevent stimulation of the D-cells = prevent somatostatin release.
Somatostatin is trying to decrease HCl secretion, so if we shut off this mechanism by buffering acid, then we are allowing more acid secretion to occur.
Peptides can also directly stimulate the G-cells to release gastrin.
Therefore:
Acidity of lumen in stomach increases before meal
More proteins increase peptides in stomach ultimately increases gastrin secretion.
Since Protein acts as a buffer. Hence proteins will decrease [H+], -> removes inhibitory powers of HCl on gastrin secretion and hence aid acid secretion.
Increased parasympathetic stimulation -> increase histamine secretion, increase gastrin secretion and act directly on the parietal cells to increase acid secretion.
This increased acid will inhibit gastrin secretion = NO HYPERSECRETION.
The luminal distension, especially when there are AA and peptides there they can stimulate gastrin secretion.
Can help take away the inhibitory effect of somatostatin. Therefore, if someone with GORD ate lots of protein it would make things worse.
Intestinal phase
This stage we want to balance things out. We want to balance the secretory activity of the stomach and the digestive and absorptive capacities of the small intestine.
The high acidity of duodenal contents as a reflex inhibits acid secretion, this is because increased acidity would inhibit the activity of digestive enzymes, bicarbonate and bile salts.
The enterogastrones are important in this control.
Distension of the duodenum, hypertonic solution, amino acids, fatty acids and monosaccharides all inhibit acid secretion.
The enterogastrones are very important in reducing the acid secretion.
Inhibition of acid secretion also depends on the composition of chyme (containing AA etc.) and volume of chyme (can cause further distension).
Short (within enteric system) and long neuronal (vagal) reflexes and hormones (enterogastrones e.g. secretin and CCK) inhibit acid secretion by the parietal cells or gastrin secretion by G cells which is inhibited by somatostatin.
There is increased sympathetic discharge which has an inhibitory effect and we turn down parasympathetic discharge.
Is HCl Essential for Life?
what conc can HCl reach? what does this depend on? (4 factors)
what 3 things does HCL do?
what does a lack of HCL do?
symptoms of HCL deficiency?
Treatmeant to stimulate HCL secretion?
What are the various HCL secretion stimulants?
What do you avoid if you have a peptic ulcer?
[HCl] can reach 150mM, this depends on
o Rate of secretion
o Amount of buffering provided by resting juice
o Gastric motility
o Diffusion back into the mucosa
HCl has roles to play in defence, it also stimulates flow of bile and pancreatic juice and also aids protein digestion by activating pepsinogen -> pepsin.
A lack of HCl causes failure of protein digestion.
Symptoms of HCl deficiency
• White spots on fingernails
• Lack of intrinsic factor
• Increase chance of H. Pylori infection
There are various treatments we can do to try and stimulate HCl secretion e.g. bitter herbs.
How can acid secretion become elevated?
There are various HCl secretion stimulants or factors that increase HCl secretion:
- Histamine
- Acetylcholine
- Gastrin
- Caffeine*
- Alcohol*
- NSAIDs*
- Nicotine*
- Helicobacter pylori
- Zollinger-Ellison syndrome (tumour secreting gastrin)
- Hyperparathyroidism
- Stress
- Bile salts
- Avoid these drugs if you have a peptic ulcer
Role of Histamine, Acetylcholine and Gastrin in Gastric Acid Secretion
what 3 molecules increase hcl secretion? where do they bind?
What effect does the binding have?
what is a canaliculus?
how does PGE2 affect HCL secretion? what 3 effects does it have?
The duodenal cells have Ach receptors.
Histamine, Ach and gastrin bind to their receptors on parietal cells which increases HCl secretion.
Activity of these hormones can cause signalling cascades by binding to their receptors which result in vesicles (tubulo-vesicle) containing H+/K+ ATPase migrating to the pits (canaliculus) to start kicking out H+
Importantly there is synergism between these stimulators of acid secretion.
PGE2 (prostaglandin E2) negatively regulates HCl secretion. It increases mucus secretion, it increases bicarbonate secretion and promotes blood flow -> inhibit the action of acid secreting stimulating molecules.
Secretion of Pepsin
what does chief cells secrete? what else is needed? how does this work?
what is the autocatalytic feedback process?
what and where is pepsin inactivated?
Pepsinogen is secreted by chief cells, it is inactive (a zymogen) in its initial state. Pepsinogen is activated to pepsin if [H+] = high, this is because pepsinogens shape is altered by high acidity which exposes its active site.
Once activated it can stimulate its own activation (autocatalytic feedback process) so once pepsinogen has been activated it can ‘go alone’.
It is inactivated upon entry of food in the small intestine (HCO3- and peptides neutralise the H+)
What stimulates the secretion of pepsinogen?
how is acid secretion and pepsinogen secretion related to each other?
what 2 things can stimulate chief cells?
what effect does H.plyori have? what does it affect more and what is the effect of this?
There are parallels between acid secretion and pepsinogen secretion, so the molecules (stimulators/inhibitors) of acid secretion during the cephalic & intestinal phases exert the same effect on pepsinogen secretion.
There is input to the chief cells from nerve plexuses -> so can be stimulated by Ach. Histamine can also stimulate chief cells.
H. pylori can affect these cells regulating acid secretion, it decreases the number of G-cells//D-cells.
The D – cells inhibit secretion and G – cells increase it but note that H. pylori affects the D-cells much more than the G-cells.
This makes sense because we know H. pylori increases acid secretion.
What is the point of pepsin secretion?
why is pepsin not absolutely required for food digestion?
what is required for vit.b12 and what is this secreted by?
It initiates the digestion of proteins and degrades food proteins into peptides, but pepsin is not absolutely required for food digestion as there are other enzymes such as trypsin, chymotrypsin etc. which can digest proteins.
Intrinsic factor is required for Vit. B¬12 and secreted by the parietal cells
How NSAIDs (e.g. aspirin) play a role in Gastric Acid Secretion Disorders?
3 damaging effects NSAIDS have on the gut?
how can NSAIDS cause haemorrhages?
what does this mean when taking aspirin?
what is NSAID-mediated gastric disorder and its effects?
NSAIDs such as aspirin cause topical irritation of the gut, this thus impairs the barrier properties of the mucosa.
NSAIDs also suppress gastric prostaglandin synthesis, this is important because the prostaglandins (PGE2) turn down acid secretion.
It also inhibits thromboxane A synthesis which is involved in repair of superficial injury and platelet aggregation.
Hence NSAIDs overall have a damaging effect on the gut and the fact you are also blocking platelet aggregation and repair makes things worse (can result in haemorrhage).
-> So, when taking aspirin must eat with food.
The presence of acid in the stomach promotes NSAID-mediated gastric disorder
o It impairs healing process, so there is more blood loss = blood in stools
o It inactivates FGF which interferes with haemostasis process
The way forward is to discover and develop stomach-sparing NSAIDs (COX2 inhibitors)
