gastric and duodenal ulcers Flashcards
peptic ulcers pathology: explain the underlying pathology of peptic ulcers
effect of H. pylori (70-80% cause of peptic ulcers) on GI environment
increases gastric acid formation, causes gastric metaplasia, decreases defence factors
what activates the proton pump which causes H+ secretion
increased Ca2+ and cAMP
effect of histamine released from enterochromaffin-like cells
bind to H3 receptors and increase cAMP
presentation of peptic ulcer
simple is most common: epigastic pain, burning sensation occuring after meals
2 investigations needed to make H. pylori positive peptic ulcer diagnosis
carbon-urea breath test (detects H. pylori), stool antigen test (confirms H. pylori)
structure of gastric antrum stomach
epithelial cells produce mucus layer to protect against acid
effect of H. pylori on mucosal layer to cause peptic ulcer
dissolves in pockets, so epithelial cells more likely to get damaged and die following acid exposure, causing peptic ulcer formation
besides epigastric pain, what is an emergency symptom due to severe peptic ulceration
severe blood loss
treatment for underlying cause of H. pylori peptic ulcer
2 antibiotics (amoxicillin and clarithromycin/metronidazole)
3rd treatment for H. pylori peptic ulcer
proton pump inhibitor to reduce acid production
features of H. pylori and significance
generally commensal gram -ve (treatment) and motile (causes multiple peptic ulcers)
how does H. pylori dissolve mucosal layer
increases gastric acid formation by increasing production of gastrin or preventing production of somatostatin
what else does H. pylori do
causes gastric metaplasia (excessive acid exposure) and downregulates defence factors (epidermal growth factor, bicarbonate production)
virulence of H. pylori
produces urease which catalyses urea into ammonium chloride and monocloramine, which damages epithelial cells
feature of urease
antigenic so evokes immune response (can be detected in stool)
what do other virulent strains of H. pylori produce
CagA (antigenic) or VacA (cytotoxic), causing more intesne tissue inflammation
presentation and investigations of chronic peptic ulcer
same as acute (acute treatment has failed)
how does H. pylori cause epithelial cell death besides dissolving mucosa to expose epithelia to acid
exotoxins and inflammation
antibiotic treatment for chronic peptic ulcer
switch one of the 2 antibiotics, and consider using quinolone or tetracycline, with the addition of chelating agents such as bismuth and sucralfate (lower acidity to prevent bacterial access to mucosa and reducing inflammation around epithelium)
other treatment for peptic ulcer
proton pump inhibitor e.g. omeprazole
how do proton pumps expressed on secretory vesicles within parietal cells work
H+-K+-ATPase pump H+ out and K+ in
mechanism by which proton pumps secrete H+
stimuli -> increase [Ca2+]i -> increase cAMP (linked to Gs protein) -> translocation of secretory vesicles to parietal cell apical surface -> H+ secretion (for K+ influx)
proton pump activity in ulcer formation
increase, increasing H+ secretion and reducing gastric pH
investigation and diagnosis for negative carbon-urea breath test and negative stool antigen test (not H. pylori)
determine whether NSAID use, which is positive
how to NSAIDs cause peptic ulcers
directly cytotoxic (irreversible inhibition of COX enzymes which produce protective effect by reducing proton pump expression), reduce mucus production, increase likelihood of bleeding, increase acidity
treatment for NSAID-causing peptic ulcer
remove NSAID (not always possible), use proton pump inhibitor or histamine H2 antagonist e.g. ranitidine
effect of H2 receptor, and antagonist
increase acid secretion, so antagonist reduces acid secretion
what causes increased expression of proton pumps: ACh
ACh released from neurones (vagus/enteric) on M3 muscarinic receptors, increases [Ca2+]
what causes decreased expression of proton pumps: prostaglandins
prostaglandins released from local cells act on EP3 receptors, decreasing cAMP
what causes increased expression of proton pumps: histamine
histamine released from enterochromaffin-like cells act on H2 receptors, increasing cAMP
what causes increased expression of proton pumps: gastrin
gastrin released from G-cells and acts on cholecystokinin B receptors, increase [Ca2+]
effect of increases in [Ca2+] and cAMP on gastric acid secretion
translocation of secretory vesicles containing proton pumps to parietal cell apical surface, increasing H+ secretion
effect of somatostain on gastric acid secretion
peptide that inhibits G-cells, enterochromaffin-like cells and parietal cells, reducing acid secretion
