Treatment of peptic ulcers Flashcards
what is standard presentation for a H pylori positive uncomplicated peptic ulcer
epigastric pain, burning sensation after meals
what are investigations you would carry out for suspected peptic ulcer
carbon urea breath test
stool antigen test
if this is a h pylori positive peptic ulcer what results would you expect
+ve carbon urea breath test
+ve stool antigen test
briefly how does h pylori cause pathology
dissolves mucus layer
causes epithelial cell death
increases acidity
= peptic ulcer
where does H pylori reside
GI tract - exclusively colonising gastric-type epithelium
describe some features of h pylori
gram -ve, motile, microaerophilic bacterium
how does h pylori increase acidity
increases gastric acid formation
by increasing gastrin and decreasing somatostatin
how does it cause damage/ changes in epithelial cells
gastric metaplasia
how does h pylori gain access to the epithelial cells
down regulate defence factors
decrease in epidermal GF and decrease in HCO3- production
what is an important virulence factor of H pylori
Urease enzyme catalyses urea into ammonium chloride and monochloramine which cause damage to epithelial cells
what other property of urease allows it to cause damage and be identified in tests
antigenic - evokes immune response
what do more virulent strains of h pylori often contain
2 genes:
CagA (antigenic)
VacA (cytotoxic)
leads to more intense tissue inflamation
what is standard treatment for a H pylori positive uncomplicated peptic ulcer
2 Antibiotics (Amoxicillin + Clarithromycin)
PPI - ompreazole
what is the difference in presentation between complicated and uncomplicated peptic ulcers
complicated: burning sensation + epigastric pain constantly
not just after meals
what additional treatment considerations are made for complicated ulcers
consider Quinolone and tetracycline in addition to other 2 antibiotics
PPI for 4-12 weeks (longer)
what is the proper name for proton pump inhibitors
H+K+-ATPase
where are proton pumps normally expressed
secretory vesicles in parietal cells
what stimulates them to secrete H+ ions and what happens to these vesicles
Increase in Ca2+ = Increase in cAMP
Translocation of secretory vesicles to parietal cell apical surface
= reduction in gastric pH
why do ulcers form (in relation to proton pump activity)
Increased activity = increased H+ secretion =
reduction in gastric pH
how would you distinguish ulcer formation due to NSAIDS instead of H pylori
If NSAID is cause:
Carbon urea test = -ve
stool antigen test = -ve
how do NSAIDS cause pathology (peptic ulcer)
directly cytotoxic
reduce mucus production
increase likelihood of bleeding
increase in acidity
treatment of peptic ulcer cause by NSAIDs
remove NSAID
PPI or H2 rc antagonist
give an example of a h2 rc antagonist
ranitidine
what 4 molecules influence gastric acid secretion (nema receptors upon which they act
Ach - M3 rc
PGs - EP3 rc
Histamine - H2 rc
Gastrin - Cholecystokinin B rc
where is gastrin released from
blood stream
where is histamine released from
EC cells
where is Ach released from
neurones (vagus/enteric)
where are PGs released from
local cells
via what mechanisms do these molecules affect Proton pumps
Ach and Gastrin: increase Ca2+
PGs and histamine: increase cAMP
why is combination therapy the best current practice
targeting multiple pathways
target multiple mechanisms of increased acid secretion
decrease resistance
treat symptoms as well as cause
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