Treatment of peptic ulcers Flashcards
Typical symptoms of peptic ulcers
- Epigastric pain
* Burning sensation that occurs after meals
Investigations following the presentation
• Carbon-urea breath test
o Detects for the presence of urea in the breath
• Stool antigen test
o Testing for the antigen against H. pylori
• 3 mechanisms by which H. pylori cause peptic ulcers
o Increased gastric acid formation –increases production of gastrin + decreases production of somatostatin
o Gastric metaplasia – cell transformation due to excessive acid exposure
o Downregulation of defence factors – reduces epidermal factor (responsible for the production of more epithelial cells) + reduction in bicarbonate production (increases the amount of acidity)
• Virulence of H pylori (3)
o Urease production Catalyses urea into ammonium chloride + monochloramine – toxic + damages epithelial cells
o Urease – antigenic
Evokes immune response, can also cause damage to the immune cells in our stomach
o Certain virulent strains have pathogenicity islands that produce CagA (antigenic) or VacA (cytotoxic)
More intense tissue inflammation
Treatment in someone with an H pylori uncomplicated peptic ulcer
• Amoxicillin + Clarithromycin/Metronidazole – antibiotics to reduce the H. pyloric infection
Treatment in someone with an H pylori complicated peptic ulcer
o Antibiotics
Amoxicillin + clarithromycin/metronidazole
Consider quinolone, tetracycline
o Protein pump inhibitor (omeprazole) – 4-12 weeks
o (addition of bismuth – acts as sucralfate)
Mechanisms of action of PPIs
• H+K+ATPase –> proton pump
• Not ordinarily expressed on the apical membranes of the cells
o If present on apical membrane –> increased acid production
o Expressed on secretory vesicles within parietal cells
o Increase in Ca –> increase in cAMP –> translocation of secretor vesicles to parietal cell apical surface –> proton pump expressed on apical membrane –> H+ secretion + K+ taken into the cell
Another cause of peptic ulcers except H pylori
NSAIDs e.g. aspirin
How do NSAIDs cause peptic ulcers
- Directly cytotoxic
- Reduces mucus production
- Increases likelihood of bleeding
- Increased acidity peptic ulcer
Treatment of H pylori negative peptic ulcer
• Removal of NSAIDs
• PPI
• Histamine H2 receptor antagonist (Rantidine) – 4-8 weeks
o H2 receptor increases acid secretion
4 types of receptors present on parietal cells
o M3RR – muscarinic receptor
o CCKB-R – cholecystokinin B receptors
o EP3-R – activated by prostaglandins (PGs)
o H2R-R – histamine receptors
How do each of the receptors on the parietal cells increase gastric acid secetion?
• Ach released from neurones (vagus/enteric) acts on M3R increase in Ca2+
• Gastrin released from blood stream acts on CCKB-R increase in Ca2+
o Increase in Ca2+ cause vesicles with protein pumps in them to move to the cell membrane increased gastric acid production + secretion
• PGs released from local cells act on E3R increase in cAMP
• Histamine released from enterochromaffin-like cells act on H2R increase in cAMP
o Increase in cAMP more vesicles with protein pumps onto the apical membrane increased gastric acid production + secretion
which receptor does H pylori primarily activate?
Responsible for increased production of gastrin so CCKB-R
which receptor does aspirin primarily activate?
H2-R (+EP3-R)
why is combination treatment the best pathway
• Targeting multiple pathways (maybe you are not sure what is the cause) more effective
• Always target PPIs
o They are always the end point of what is increasing the acid secretion
• PPI also improves antibiotic efficiency by increasing gastric pH improves stability + absorption
• Antibiotic resistance could arise
