Secretions of the Stomach Flashcards
what are the functions of the stomach?
Stores food
Mixes food with the gastric secretions it produces
Regulates release of food into duodenum via pyloric sphincter
One-way valve: Regulates release into duodenum and supresses reflux of duodenal contents back into stomach
what is the body of the stomach called?
what is a feature of the antrum?
Corpus: Body of stomach
The Antrum has a thickened muscled wall so it can grind contents of stomach so they are small enough to pass through the duodenum.
what are the cell types in the stomach?
(including secretory product, inhibition and stimulation)
Body of stomach contains mainly parietal & chief cells with some ECL (enterochromaffin-like) & D cells
Acid production occurs in the body of the stomach.
Antrum contains G & D cells, with no parietal cells
what is the mechanism of acid secretion by parietal cell?
Mediated by H+/K+ pump (requires energy), located in the apical membrane of parietal cells
The H-K pump requires both an alpha subunit (for catalytic function) and a Beta subunit (apical membrane targeting) for full activity.
H-K pump (using ATP) extrudes H+ into the lumen of gastric gland (branched tubules in the inner lining of the stomach) in exchange for K+.
The H+ combines with Cl- that has left cells through ion channels to form HCl
K+ is then recycled back into the lumen via K+ channels
Original H+ that is pumped into lumen is generated from carbonic acid (produce with action of carbonic anhydrase)
The remaining HCO3- exits the cell across basolateral membrane via Cl– HCO3- exchanger and the bicarbonate ion ends up in the blood.
This means every time the stomach pumps a proton into the lumen of the stomach a bicarbonate ion ends up in the blood. This is known as the alkaline tide.
Temporary increase in blood pH - normally after a meal
https://www.youtube.com/watch?v=W9nyXXh8htM - very useful video!
what regulates acid secretion by parietal cell?
Direct Regulation: (action triggers proton efflux via H+/K+ pumps):
ACh
Source: vagus nerve as a neurotransmitter
NT is released in response to when you have a meal and the stomach stretches.
Binds to M3 receptor which stimulates parietal cells to produce acid
Histamine:
Produced by ECL cells
Binds to H2 receptor on parietal cells and triggers acid production.
Gastrin:
Produced by G cells.
Binds to Gastrin receptor on parietal cells and stimulates acid production
Indirect: ACh & gastrin also induce the release of histamine by ECL cells which stimulates the parietal cells.
Histamine contributes most to acid production due to direct & indirect effects
explain how histamine, gastrin and ACh interact with receptors on parietal cells
Histamine binds to a H2 receptor which then via a adenyl cyclase-camp-PKA pathway stimulates H+/K+ pumps
Gastrin binds to gastrin receptor and then via (PLC/PKC)/Ca2+ stimulates H+/K+ pumps
Ach binds to M3 receptor and then via (PLC/PKC)/Ca2+ pathway stimulates H+/K+ pumps
Major inhibitor for acid production is somatostatin which binds to somatostain receptor and antagonises adenyl cyclase pathway (predominantly acting by inhibition of histamine)
what process occurs in the corpus of the stomach?
ACh is released from the vagus nerve due to distension of stomach
Direct stimulation of parietal cells to induce acid release
Indirect stimulation of parietal cell by causing ECL cells to release histamine
Stimulates D cell which inhibits the release of somatostatin
what process occurs in the antrum?
G Cells:
Vagal stimulation of G cells, via GRP (not Ach) (Gastrin releasing peptide) stimulates G cells to begin to produce gastrin.
Gastrin triggers parietal cells to produce acid directly and indirectly via ECL cells.
In addition, G cell can sense components of the lumen in the antrum. Once proteins are broken down by pepsin the peptides and amino acids are sensed by G cell. The G cell is then stimulated to produce gastrin.
D Cells:
Vagal stimulation of D cells via Ach inhibits the release of somatostatin.
what are the Inhibitors of acid secretion?
Somatostatin: released by D cells - stimulated by a low luminal pH in antrum
Somatostatin inhibits acid secretion by binding to somatostatin receptor on parietal cell of basolateral surface.
Somatostatin will also inhibit ECL cells from making histamine so they can’t stimulate parietal cell.
Somatostatin also acts on G cells which inhibits gastrin release from G cells.
Secretin: Released by duodenal S cells - stimulated by fat & acid in duodenum
Inhibits acid secretion by:
- Inhibiting antral gastrin release
- Promotes somatostatin release
- Cholecystokinin (CCK): produced by I cells (in brush wall of small bowel) of duodenum & jejunum in response to fat
- Directly reduces parietal cell acid secretion
what are some pharmacological inhibitors of acid secretion?
Proton pump inhibitors (i.e. omeprazole)
Directly inhibit the pump itself
H2 receptor antagonists (cimetidine & ranitidine)
Competitive antagonists of histamine at parietal cell H2 receptors
Inferior to PPIs as even if you supress histamine you can still stimulate acid production via ACh and gastrin.
However H2 receptor antagonists are used because histamine is a big contribution to acid production.
PPIs & H2 RAs used in treatment of peptic ulcer disease, dyspepsia, GORD, BM, Zollinger-Ellison syndrome
In the olden days highly selective vagotomies (remove part of vagus nerve) were performed as they oblate ACh mediate acid production. However, vagotomies impact motilities and gastric emptying so were not good approach.
list the phases of gastric acid secretion
- Basal phase
Acid secretion is low and follows circadian rhythm (low am; high pm)
The level of acid secretion dependent on no. of parietal cells (i.e. size of stomach) - Cephalic phase (30% of acid secretion)
Occurs before food enters stomach
Smell, sight, taste & swallowing of food initiate secretion of acid - mediated by vagus nerve - Gastric phase (50-60% total acid secretion)
Food in stomach –> distension of stomach by food stimulates Ach release via vagus nerve (stimulates, ECL cell and parietal cell) and GRP release via vagus nerve (GRP stimulates G cell and ECL cell)).
Also, products of the digestion of proteins (peptides and amino acids) stimulate G cells to make gastrin.
These all result in parietal cell making more acid. - Intestinal phase 5-10% gastric acid secretion
Partially digested peptides/AAs in proximal portion of small intestine stimulate acid secretion by stimulation of duodenal G cells –> produce gastrin –> enter stomach and stimulate acid production.
what are Pepsinogens?
Pepsinogens are proteolytic proenzymes (inactive) secreted by chief cells
ACh is the major trigger for pepsinogen secretion.
Activation: Conversion of pepsinogen -> pepsin (occurs spontaneously at pH<5 (most active at pH<3))
Pepsin autoactivates pepsinogen –> cascade effect
Pepsin is irreversibly inactivated at pH 7.2 (small intestine)
Pepsin is an endopeptidase which initiates protein digestion
The secretion of pepsinogens is interlinked with acid secretion due to similar trigger (ACh) & resulting peptides trigger antral G-cell gastrin secretion
Makes sense as when you have eaten you want to produce acid and also start digestion as well.
explain how gastric mucosal protection occurs
The contents of stomach lumen create a harsh environment (pH<1, and you have pepsin)
Protection comes in the form of the mucous layer (on the surface of mucosa), produced by mucous neck cells which traps local HCO3- secretion –> maintains the mucous layer at pH 7 (approx.)
Therefore, the immediate layer above the epithelium is not in contact with harsh environment (protected by mucous layer)
Prostaglandins contribute towards protection by maintaining mucosal diffusion barrier
They inhibit acid secretion, and stimulate HCO3- & mucous secretion.
When NSAIDs are taken chronically they can lead to gastric mucosal ulcers and damage to stomach as they inhibit prostaglandin synthesis…
what are Prostaglandins and how are they made?
The stomach needs to have a protective mechanism this happens via mucous layer and PG maintain this.
PG are synthetised by various phospholipids. These are converted into arachidonic acids which are precursors.
Arachidonic acids are converted into PG (by COX-1 enzyme).
These PG are important in physiology including gastric mucosa protection.
Arachidonic acid can also be converted by COX-2 enzyme into inflammatory PG.
NSAIDs inhibit PG production by inhibiting COX-1 (not intended) & COX-2 (intended effect to reduce inflammation)
Therefore, chronic users of NSAID can develop gastric ulcers.
Vioxx is a drug which selectively only inhibits COX-2 pathway. It was used to treat arthritis and acute pain conditions but it was withdrawn as there was too many side effects e.g. increased risk of heart attack.
what is Helicobacter pylori?
Gram-negative microaerophilic bacterium
Classified as a carcinogen.
This acid loving disease colonised the stomach of 40% of humans
Can cause gastritis, peptic ulcers, & gastric cancer
Mechanism of causing peptic ulcers:
H. Pylori has a flagellum to move to the mucous layer of the stomach/duodenum.
It produces mucinase which allows it to break down mucin. This weakens the protective mucus coating of the stomach/duodenum.
This allows H. Pylori to get very close to the gastric mucosal cells and adhere via lipopolysaccharides.
It also allows acid to get close to gastric mucosa.
The combination of these results in the development of peptic ulcer.
