gastric physiology 1: peptic ulcers and parietal cells Flashcards
functions of stomach
- Store and mix food
- Dissolve and continue digestion
- Regulate emptying into duodenum
- Kill microbes
- Secrete proteases
- Secrete intrinsic factor (made by parietal cells, important because it binds to B12 to allow absorption in ileum)
- Activate proteases
- Lubrication
- Mucosal protection
key cells in the stomach
mucous cells, parietal cells, chief cells, enteroendocrine cells
Gastric acid secretion
- Hydrochloric acid
- Approx 2 litres/day
- [H+] >150mM
- Parietal cells
- Energy dependent
- Neurohumoral regulation
regulating gastric acid secretion
turning it on (Cephalic phase)
- Parasympathetic nervous system
- Sight, smell, taste of food, and chewing
- Acetylcholine release
- ACh acts directly on parietal cells
- ACh triggers release of gastrin and histamine
- Net effect = increased acid production
regulating gastric acid secretion
turning it on (Gastric phase)
• Gastric distension, presence of peptides and amino acids
• Gastrin release
• Gastrin acts directly on parietal cells
• Gastrin triggers release of histamine
• Histamine acts directly on parietal cells
• Net effect = increased acid production
Histamine is therefore really important!
Acts directly but also mediates effects of gastrin and acetylcholine
Perhaps then a good therapeutic target?
regulating gastric acid secretion
turning it on (protein in the stomach)
Direct stimulus for gastrin release
Proteins in the lumen act as a buffer, mopping up H+ ions, causing pH to rise:
o decreased secretion of somatostatin
o more parietal cell activity (lack of inhibition)
turning it off (gastric phase)
Low luminal pH (high [H+])
o Directly inhibits gastrin secretion
o Indirectly inhibits histamine release (via gastrin)
o Stimulates somatostatin release which inhibits parietal cell activity
turning it off (intestinal phase)
In the duodenum:
• Duodenal distension
• Low luminal pH
• Hypertonic luminal contents
• Presence of amino acids and fatty acids
Trigger release of enterogastrones:
o Secretin (inhibits gastrin release, promotes somatostatin release)
o Cholecystokinin (CCK)
And short and long neural pathways, reducing ACh release
summary of parietal cells and acid secretion
controlled by brain, stomach, duodenum
• 1x (parasympathetic) neurotransmitter (ACh +)
• 1x hormone (gastrin +)
• 2x paracrine factors (histamine +, somatostatin -)
• 2x key enterogastrones (secretin -, CCK -)
peptic ulcers definition and causes
Causes: • Helicobacter pylori infection • Drugs – NSAIDS • Chemical irritants – alcohol, bile salts, ? Dietary factors • Gastrinoma
why ulcers form
increased mucosal attack and/or reduced mucosal defence
how does the gastric mucosa defend itself?
- Alkaline mucus
- Tight junctions between epithelial cells
- Replacement of damaged cells
- Feedback loops
Helicobacter pylori
- Lives in the gastric mucus
- Secretes urease, splitting urea into CO2 + ammonia
- Ammonia + H+ = Ammonium
- Ammonium, secreted proteases, phospholipases and vacuolating cytotoxin A damage gastric epithelium
- Inflammatory response
- Reduced mucosal defence
NSAIDs
- Non-steroidal anti-inflammatory drugs
- Mucus secretion is stimulated by prostaglandins
- Cyclo-oxygenase 1 needed for prostaglandin synthesis
- NSAIDs inhibit cyclo-oxygenase 1
- Reduced mucosal defence
Bile salts
- Duodeno-gastric reflux
- Regurgitated bile strips away mucus layer
- Reduced mucosal defence
