29. Treatment of gastric and duodenal ulcers Flashcards
How can we test for H. pylori?
Carbon-urea breath test
• Give patient a lot of urea
• H. pylori metabolises urea to nitrogen
• Increased levels of nitrogen - positive
Stool antigen test
• Test for H. pylori antigens
What percentage of duodenal and gastric ulcers are a result of H. pylori infection?
- Duodenal - 98-100%
* Gastric - 70-80%
Is H. pylori commensal?
Yes, in the majority of people
How does H. pylori cause peptic ulcers?
- Dissolves mucus layer using urease, to access epithelia
- This exposes epithelial cells and leaves them more susceptible to the acidic environment
- Epithelial cell death
- H. pylori releases exotoxins - increased inflammatory reaction (antigenic)
- Damage goes down to the interstitial layer
- Ulcer formed
- Acid exposure can also cause gastric metaplasia
• Increased gastric acid formation
- increased gastrin and decreased somatostatin
• Down-regulation of defence factors
- decreased epidermal GF and decreased bicarbonate production
Which type of cells are mainly affected by H. pylori?
Parietal cells in the stomach
What does urease catalyse?
Urea => ammonium chloride + monochloride
What does CagA and VacA refer to?
- Different strains of H. pylori
- CagA are more antigenic
- VacA are more cytotoxic
How can peptic ulcers due to H. pylori be treated?
Amoxicillin + clarithromycin/metronidazole
• Antibiotics
• 2 drug combination is very effective
• Stomach can heal itself very well after
Proton pump inhibitor
• Reduces acid production
• Given for 7 days
What investigation do we do if there is epigastric pain and a constant burning sensation (not just after meals), and the H. pylori tests are positive? What is the most likely diagnosis?
- Endoscopy
* Complicated peptic ulcer
What can bismuth be used for?
Protect mucus layer
How long are PPIs given for complicated peptic ulcers?
4-12 WEEKS
What antibiotics are given for complicated peptic ulcers?
- Usual 2 drug combination, or even 3
- Consider quinolone/tetracycline
- May be added alongside first line antibiotics
Which systems are the main regulators of the parietal cells producing H+?
Cholinergic and histaminergic system in the stomach
How does somatostatin and gastrin (released in the stomach fundus) affect parietal activity?
- Somatostatin reduces parietal cell activity
* Gastrin increases parietal cell activity
What is the second most common cause of peptic ulcers?
Prolonged NSAID usage
What can bismuth be used for?
Protect mucus layer
How long are PPIs given for complicated peptic ulcers?
4-12 WEEKS
What antibiotics are given for complicated peptic ulcers?
- Usual 2 drug combination, or even 3
- Consider quinolone/tetracycline
- May be added alongside first line antibiotics
Which systems are the main regulators of the parietal cells producing H+?
Cholinergic and histaminergic system in the stomach
Describe the regulation of gastric acid in the stomach (4 ways)
1) ACh released from vagus/enteric (parasympathetic) neurones acts on muscarinic (M3) receptors
- increased [Ca2+]
- vesicles with H+K+ATPase moves to apical membrane
- more PP => more acid
2) Prostaglandins from released from local cells act on EP3 receptors
- decreased cAMP
- decreased vesicle migration and acid release
3) Histamine released from enterochromaffin-like cells act on H2 receptors
- increased cAMP
- increased vesicle migration and acid release
4) Gastrin released from blood stream acts on cholecystokinin B receptors
- increased [Ca2+]
- increased vesicle migration and acid release
How can NSAIDs cause peptic ulcers?
- Can be directly cytotoxic
- Reduce mucus production
- Anti-platelet - increase likelihood of bleeding
How can peptic ulcers due to NSAIDs be treated?
- Remove NSAID drugs
* PPI or histamine H2 receptor antagonist (ranitidine)
How do H2 receptor antagonists treat peptic ulcers?
- H2 receptor stimulation increases (PP activity and) acid secretion
- Located on parietal cell
- Antagonism decreases acid secretion
Are PPIs always prescribed for peptic ulcers, regardless of aetiology?
Yes
Describe the regulation of gastric acid in the stomach
1) ACh released from vagus/enteric (parasympathetic) neurones acts on muscarinic (M3) receptors
- increased [Ca2+]
- vesicles with H+K+ATPase moves to apical membrane
- more PP => more acid
2) Prostaglandins from released from local cells act on EP3 receptors
- increased cAMP
- increased vesicle migration to apical surface
3) Histamine released from enterochromaffin-like cells act on H2 receptors
- increased cAMP
- increased vesicle migration to apical surface
