Gastric Physiology 1: Parietal cells and peptic ulcers Flashcards
What are the functions of the stomach?
- Store and mix food
- Dissolve and continue digestion
- Regulate emptying into duodenum
- Kill microbes
- Secrete proteases
- Secrete intrinsic factor
- Activate proteases
- Lubrication
- Mucosal protection
What does intrinsic factor do?
Helps absorb Vitamin B12
What does mucosal protection do?
Stops stomach digesting itself
What are four key cell types in the stomach lining?
- Mucous cells
- Parietal cells
- Chief cells
- Enteroendocrine cells
What do Parietal cells secrete?
- Secrete HCl
- Secrete intrinsic factor
What do chief cells secrete?
Secrete proteases
What do enteroendocrine cells secrete?
Hormones, they are a type of epithelial cells
What acid is gastric acid secretion?
Hydrochloric acid
(secrete approx 2 litres/day)
What ion is pumped out in gastric acid secretion?
H+ is pumped out at a very high concentration against a concentration gradients so it is very energy dependent
What is HCl secretion regulated by?
- Neural (via vagus nerve)
- Hormones
What ions are pumped out of the parietal cell and into the stomach lumen?
K+, Cl-, H+
What ions are pumped from the stomach lumen into the parietal cell?
K+
Which ions don’t require any energy to be pumped (e.g. passive diffusion)?
- K+ going into parietal cell
- Cl- being pumped out of cell
Where are the H+ ions that are being pumped out of cell coming from?
- From cellular respiration
- From the formation of H2CO3 from CO2 and H20
- H2CO3 then broken down into HCO3 and H+ ions
What ions are pumped into parietal cell from capillary and vice versa?
- HCO3- pumped out of cell and into capillary
- Cl- pumped into parietal cell from capillary
What is the cephalic phase of gastric acid secretion?
It is turning it on phase and part of regulation
What activates the cephalic phase?
- Parasympathetic nervous system
- Sight, smell, taste of food and chewing
What does the release of acetylcholine do during the cephalic phase?
- It is a neurotransmitter (through the vagus nerve to the stomach)
- Acts directly on parietal cells
- Triggers the release of gastrin and histamine (which turns parietal cells on)
What does the release of acetylcholine do during the cephalic phase?
- It is a neurotransmitter (through the vagus nerve to the stomach)
- Acts directly on parietal cells
- Triggers the release of gastrin and histamine (which turns parietal cells on
What is the net effect from the release of acetylcholine in the cephalic phase?
Increased acid production (HCl)
What stimulates the turning on during the gastric phase?
- Gastric distension (stretching)
- Presence of peptides and amino acids
What is released during the gastric phase?
Gastrin (hormone)
What does the release of gastrin do in the gastric phase?
- Acts directly on parietal cells
- Triggers the release of histamine (which acts directly on parietal cells)
- The net effect is an increase in acid production
What does histamine do?
- Acts directly on parietal cells
- Mediates the effects of gastrin and acetylcholine
What does having protein in the stomach do?
Direct stimulus for gastrin release
What do proteins in the lumen do?
- Acts as a buffer, mopping up H+ ions, causing pH to rise (which further increases HCl production)
- Decreases the secretion of somatostatin (turns parietal cells off) so a decrease in this means more parietal cell activity
What stimulates the turning off of gastric secretion in the gastric phase?
- Low luminal pH (high H+ ions)
What happens in order to turn off gastric acid secretion in the gastric phase?
Having a low luminal pH…
- Directly inhibits gastrin secretion
- Indirectly inhibits histamine release (via gastrin)
- Stimulates somatostatin release which inhibits parietal cell activity
What are the stimuli in the duodenum that turns off gastric acid secretion?
- Duodenal distension (stretching)
- Low luminal pH
- Hypertonic luminal contents (large number of ions)
- Presence of amino acids and fatty acids
Duodenum senses these and sends message to stomach to turn off via hormone (enterogastrones)
What does the release of enterogastrones do?
- Secretin released (inhibits gastrin release, promotes somatostatin release)
- Cholecystokinin (CCK)
- Short and long neural pathways, reducing the Acetylcholine release (because the duodenum is innervated by vagus nerve)
Conclusion: What affects the gastric acid secretion?
- 1 parasympathetic neurotransmitter (ACh +)
- 1 hormone (gastrin +)
- 2 paracrine factors (histamine +, somatostatin -)
- 2 Key enterogastrones (secretin -, CCK-)
+ turns stomach on - turns stomach off
What is autocrine factor?
Acts on own cell surface
What is a paracrine factor?
Cells talk to neighbouring cells
What does a hormone do?
Acts of other cells at a distant sites
What is the definition of an ulcer?
It is a breach in a mucosal surface
So a peptic ulcer is one caused by gastric enzymes
What bacteria causes peptic ulcers?
Helicobacter Pylori infection
What else can cause peptic ulcers?
- Drugs (NSAIDS e.g. aspirin, ibuprofen)
- Chemical irritants (alcohol, bile salts)
- Gastrinoma (tumours of enteroendocrine cells that produce gastrin)
What can cause an ulcer in terms of mucosal attack/defence?
- Normal defences sufficient to resist attack means no ulcer
- Increased mucosal attack creates an ulcer
- Reduced mucosal defence creates an ulcer
How does the gastric mucosa defend itself?
- Alkaline mucus (So can resist acid attack)
- Tight junctions between epithelial cells (prevents liquid getting into tissues)
- Replacement of damaged cells (so epithelial stays in tact)
- Feedback loops prevent overproduction of gastric acid
Where does helicobacter pylori live?
In gastric mucus
How does helicobacter pylori cause a reduced mucosal defence?
- Secretes urease, splitting urea into CO2 and ammonia
- Ammonia reacts with H+ ions and forms ammonium which is toxic to gastric epithelium
- Ammonium secretes proteases, phospholipases which damage gastric epithelium
- This causes an inflammatory response
- Reducing mucosal defence
How do NSAIDs cause peptic ulcers?
- Non-steroidal anti-inflammatory drugs
- Mucus secretion is stimulated by prostaglandins
- Cyclo-oxygenase 1 needed for prostaglandin synthesis (important in inflammatory process)
- NSAIDs inhibit cyclo-oxygenase 1
- Reduced mucosal defence
- So increased risk of peptic ulcers
How do bile salts create peptic ulcers?
- Duodeno-gastric reflux (throwing up bile)
- Regurgitated bile strips away mucus layer
- Reduced mucosal defence
How to treat peptic ulcer disease?
- proton pump inhibitor
- antibiotics (e.g. amoxicillin)
How to treat a peptic ulcer caused by NSAIDs?
- Prostaglandin analogues - misoprostol (stimulates gastric mucus production)
- Reduce acid secretion
- Could also use proton inhibitor
What are some proton pump inhibitors?
Omeprazole, Lansoprazole, Esomeprazole
What are some H2 (Histamine) receptor antagonists?
Cimetidine, Ranitidine
