24: Peptic Ulcers Flashcards
What is a typical presentation of someone with a gastic/duodenal ulcer?
Epigastric pain, burning sensation (that occurs after meals)
How would you determine, whether a peptic ulcer is h.pyloria +ve or negative?
- Carbon-urea breath test
- Stool antigen test
What are the effects (not the mechanisms) of how H pylori causes peptic ulcers?
- Dissolves the protective mucus layer
- which Causes epithelial cell death
- Increased acidity –> peptic ulcer
How would you normally treat a H.pylori +ve Peptic ulcer?
Triple therapy
- 2 ABX (e.g. Amoxicillin & Clarithromycin/Metronidazole)
- PPI
Which is a combined triple therapy the chosen treatment for peptic ulcers?
Because it is more effective because it eleminates the cause (bacterial infection) whilst also reducing acid production in the parietal cells –> limiting damage
What kind of bacteria is H pylori?
Helicobacter Pylori
- Gramm -ve
- motile
- microaerophilic bacterium
- that Resides in human GI tract and exclusively colonises gastric-type epithelium
Explain the mechanisms by which H pylori can cause gastic ulcers
It produced different substances:
- Main enzyme: Urease – catalyses urea into ammonium chloride & monochloramine –> damage epithelial cells
- Urease – antigenic –> evokes immune response
- Certain virulent strains produce CagA (antigenic - attract more immune cells ) or VacA (directly cytotoxic) – more intense tissue inflammation
What are the effects of the catalysation by Urease on the stomach?
Make Stomach more acidic and less protective
- Increased gastric acid formation – + gastrin or - somatostatin
- Gastric metaplasia – cell transformation due to excessive acid exposure
- •Downregulation of defence factors –> epidermal growth factor & ¯ bicarbonate production (loss of protective mutive)
In a persistent, chronic H.pylori +ve gastric ulcer, how would you treat the patient?
Should already be on Triple Therapy
- Then Change the ABX (Consider quinolone, tetracycline)
Explaint the regulation of Proton Pumps in the stomach
Which role does it play in gastric ulcer formation?
Are present on secretory vesicles within parietal cells
- increase in intracellular Ca2+ –> cAMP leads to a translocation of secretory vesicles to parietal cell apical surface ® H+ secretion
–> Often increased in gastic ulcers–> low pH
Explain the effects of NSAIDs on the GI tract
NSAID –> might lead to the formation of gastic ulcers via
- Directl cytotoxicity (Cox interference)
- Reduced mucus production
- Increased likelihood of bleeding (blood thinning)
–> Increased acidity –> peptic ulcer
How would you treat a H.pylori -ve peptiv ulcer in someone using NSAIDs?
- If possible (if otherwise not getting a stroke etc.)
- remove NSAIDs
- PPI or Histamine H2 antagonist (e.g. Ranitidine)
Name a H2 histamine receptor antagonist and explain its MOA
E.g. Ranitidine
- Normally: Binding to H2 receptor causes
- increase in cAMP
- increase in Acid secretion
- If antagonsit: reduced gastric acid secretion
- Not necessarily needed if PPI are tolerated (they are also cheap and effective)
How does Ach modulates Gastric acid secretion?
1.Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors —> increase [Ca2+]i
–> increased acid production
How do prostaglandins modulate gstric acid secretion
- Prostaglandins (PGs) released from local cells act on EP3 receptors - ↓ cAMP
* reduce secretion and are protective (also inhibited in the use of NSAIDs)
How does Gastrin modulate Gastric acid secretion`
1.Gastrin released from G-cells, acts on cholecystokinin B receptors –> increase [Ca2+]
