Treatment of peptic ulcers Flashcards
Common presentation of peptic ulcer
Epigastric pain, burning sensation after meals
Investigations of peptic ulcer
Carbon-urea breath test
Stool antigen test (H pylori)
Pathophysiology of H pylori positive peptic ulcer
H pylorus:
- dissolves mucus layer (epithelial cells more susceptible to damage from the acidic environment of stomach)
- epithelial cell death
ULCER
Treatment of h pylori positive peptic ulcer
Antibiotics for H Pylori (amoxicillin &
clarithromycin/metronidazole)
Proton Pump Inhibitor reduces acid production
What type of bacterial is helicobacter
Gram negative, motile, microaerophilic bacterium
Where does H pylori reside
Resides in human GI tract – exclusively colonising gastric-type epithelium
How does H pylori affect the GI tract to lead to ulcer formation
- Increased gastric acid formation
- Gastric metaplasia
- Downregulation of defence factors
How does H pylori increase acid formation
Increase gastrin or reduce somatostatin
How does H pylori downregulate defence factors
Reduces epidermal growth factor and decreases bicarbonate production
How does H pylori cause gastric metabplasm a
(cell transformation due to excessive acid exposure)
What is the virulence of H pyori
Urease
and
Certain strains produce CagA or VacA
How does urease from H pylori cause virulence
- catalyses urea into ammonium chloride &monochloramine –>
damage epithelial cells
- Urease is antigenic and evokes immune response
How do CagA and VacA cause virulence in H Pylori
Certain virulent strains produce CagA (antigenic response) or VacA (cytotoxic response) – more intense tissue inflammation
What differentiates acute and chronic peptic ulcer
Acute- just pain and burning after food
Compicated- constant pain and burning
Treatment for complicated peptic ulcer
Antibiotics for H Pylori (amoxicillin & clarithromycin/metronidazole)
Consider quinolone, tetracycline
Proton Pump Inhibitor (omeprazole) – 4-12 weeks
How to proton pumps work
Acid from parietal cells
H+-K+-ATPase
Expressed on secretory vesicles within parietal cells (NOT USUALLY EXPRESSED ON THE CELL MEMBRANE, UNTIL ACTIVATION)
What leads to acid secretion
Increased [Ca2+], inreased cAMP, translocation of secretory vesicles to parietal cell apical surface, leads to H+ secretion
What can occur in ulcer formation with proton pump
Increased activity of proton pump – increased H+ secretion leads to reduction gastric pH
After H pylori, what is the next most common cause of peptic ulcer
NSAID
How can NSAID induce peptic ulder
Directly cytotoxic
Reduces mucus production
Increases likelihood of bleeding
Increased acidity leads to peptic ulcer
Treamtent for NSAID related peptic ulcer
Removal of NSAID
Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks
H2 receptor increases acid secretion
NO ABs!!!!
4 main types of receptors on the parietal cells, the agonists, and where these agonists come from
- M3-R (ACh, neurons)
- EP3-R (PGs, local cells)
- H2-R (Histamine, ECL cell)
- CCKB-R (Gastrin, bloodstream)
Outline the action of the ACh receptor for gastric acid regulation
Released from vaus of enteric nerves–> Increased [Ca2+]
Outline the action of the prostaglandngs receptor for gastric acid regulation
Increasing cAMP
Outline the action of histamine receptor on gastric acid regulation
Increasing cAMP
How does action of gastrin affect fastric acid regulation
Gastrin released from blood stream acts on cholecystokinin B receptors - increass [Ca2+]i
What can result in the increased gastric acid secretion
inreased [Ca2+]i & increased cAMP leads to translocation of secretory vesicles to parietal cell apical surface leads to H+ secretion
How does H pylori lead to
i. Dissolve of mucus layer
ii. Epithelial cell death
i. Urease enzyme
ii. exotoxins (cagA, vacA) and inflammation
