Gastric Physiology 1 Flashcards
Functions of the stomach
Store and mix food
Dissolve and continue digestion
Regulate emptying into duodenum as the stomach has a much larger volume than the other parts of the GI, especially the duodenum
Kill microbes by secreting HCl
Secrete proteases
Secrete intrinsic factor which binds to vitamin B12 to help absorb vitamin B12 in the terminal ileum
Intrinsic factor is secreted by the parietal cells And the stimuli for the production of intrinsic factor are the same as the stimuli for the production of the HCl acid
Activate proteases
Lubrication as the epithelium is fragile and so needs to be protected against the abrasive forces
Mucosal protection to protect the stomach from digesting itself
Key cell types in the gastric epithelium
The lining of the stomach is as a flat epithelium that’s been thrown into deep pits
The flat part of the stomach and the neck of these puts are aligned by mucus secreting epithelial cells
-Mucus is important in gastric protection
In the fundus and the body of the stomach the pits are lined in part by parietal cells- release HCl acid and intrinsic factor
Chief cells- produce proteases
Wide variety of different enteroendocrine cells- These are epithelial cells, but they secrete hormones and there’s a variety of different hormones that they produce
In the stomach the G cells secrete gastrin, a hormone produced in the stomach
Gastric acid secretion
Approx 2Litres/day of HCl acid is produced by stomach
Therefore the stomach is going to need to pump Hydrogen ions at a high concentration (above 150mM multiple times during the day against the concentration gradient
So this process requires energy
Under neurohumoral regulation- HCl acid secretion/gastric acid secretion is done through a mixture of neural input to the stomach, delivered primarily through the vagus nerve and a range of different hormones
This must be turned on and off in balance
Gastric acid secretion
HCl made by parietal cells.
• H2O and CO2 combine with the parietal cell cytoplasm to produce carbonic acid (H2CO3)
- catalysed by the enzyme carbonic anhydrase
• Carbonic acid dissociates into a hydrogen ion (H+) and a bicarbonate ion (HCO3-).
Hydrogen ion enters the lumen of the stomach via an H+ - K+ ATPase on the apical membrane. This channel uses ATP to exchange K+ ions in the stomach with H+ ions in the parietal cell.
• Bicarbonate ion is transported out of the cell into the blood in exchange for a chloride ion (Cl-), using an anion exchanger located on the basolateral membrane.
• Chloride ion transported into the stomach lumen through a chloride channel
• Both H+ ions and Cl- ions in the lumen of the stomach – they have opposite charges, so associate with each other to form hydrochloric acid (HCl)
Turning this process of gastric acid secretion on- CEPHALIC PHASE
Prior to eating, the thought, chewing, smell, sight of food stimulates the brain to stimulate the stomach via the vagus nerve to start to produce gastric acid
It does that through the release of acetylcholine, a neurotransmitter from parasympathetic nerve fibres conveyed through the vagus nerve to the stomach as ACh can directly act on parietal cells and turn them on at least to the upregulation of the production of those hydrogen pumps
This can also occur indirectly; It can act on the enteral endocrine cells in the stomach to trigger them to release gastrin, which turns parietal cells on
It can also act on other entraendocrine cells and on mast cells within the stomach to make them produce histamine. Histamine also acts on parietal cells and turns them on, makes them regulate the production of hydrogen, potassium, atpase pumps or proton pumps to produce gastric acid.
Net effect of seeing, smelling or chewing food tuns on HCl production
Turning this process of gastric acid secretion on- GASTRIC PHASE
The prior process must continue once there is food in the stomach
Once there are peptides and amino acids in the stomach that stimulates the stomach to start it turn on gastric acid- gastric distension
Gastrin is then released
Gastrin still acts directly on parietal cells
Gastrin triggers release of histamine
Histamine then acts directly on parietal cells
This results in a net effect of increased acid production
Histamine is therefore important- acts directly but also mediates the effects of Gastrin and acetylcholine
Turning this process of gastric acid secretion on- PROTEINS IN THE STOMACH
Direct stimulus for Gastrin release
Proteins in the lumen act as a buffer, mopping up H+ ions, causing pH to rise. This leads to
-Decreased secretion of somatostatin, so less inhibition of the production of gastric acid
-More parietal cell activity (lack of inhibition)
Turning off gastric acid secretion- GASTRIC PHASE
This is achieved by having a low pH in the stomach (high H+ ions). This:
-Directly inhibits Gastrin secretion
-Indirectly inhibits histamine release (via Gastrin)
-Stimulates somatostatin release which inhibits parietal cell activity - this limits how low the pH in the stomach can be taken (down to pH 2)
Turning off gastric acid secretion- INTESTINAL PHASE
This is achieved by duodenum recognising when the gastric contents have entered it by stretching as detects
-Duodenal distension
-Low luminal pH
-Hypertonic luminal contents
-Presence of amino acids and fatty acids
This triggers the release of enterogastrones:
-Secretin (inhibits Gastrin release, promotes somatostatin release)
-Cholecystokinin (CCK)
These both hormones act to promote the secretin of somatostatin by the stomach which then turns the stomach off
The duodenum is innervated by the vagus nerves and so it will send neural pathways back to the brain and then back to the stomach through the vagus nerve to turn the stomach off by reducing the amount of acetylcholine being released
Regulation of gastric acid secretion is
On the basal surface of the parietal cell there are receptors to Gastrin, acetylcholine, histamine and somatostatin.
These receptors act through a cascade of secondary messengers within the parietal cell.
The net effect of these receptors is usually the up-regulation of the production of proton pumps, which can be expressed on the luminal cell surface
Controlled by the brain, stomach and duodenum
1 (Parasympathetic) neurotransmitter (ACh +)
1 hormone (Gastrin +)
2 paracrine factors (histamine +, somatostatin -)
2 key enterogastrones (secretin -, CCK -)
Peptic ulcers-definition
An ulcer is a breach in a mucosal surface
Peptic ulcers- causes
Helicobacter pylori infection
Drigs- NSAIDS
Chemical irritants- alcohol, bile salts, dietary factors
Gastrinoma- tumours of the enteroendicrine cells that lead to hypoacidicty and peptic ulcers
What occurs normally?
Normally our stomach is under constant attack by the acid that it secretes and the enzymes that it secretes, but defends itself against them
So if the defences of the mucosa are strong enough
to meet the attack, no ulcers
Two ways that an ulcer can be caused
Increasing the amount of attack on the mucosa or by reducing the mucosa defence
How does the gastric mucosa defend itself?
Produces alkaline mucus so it can resist acid attack
Tight junctions between the epithelial cells of the stomach that prevents liquid contents if the stomach getting into the underlying tissues
Rapidly replaces cells that have died or been lost so that it keeps the epithelium intact
Uses feedback loops to prevent the overproduction of gastric acid
