Unit 9 - Peptic ulcer Flashcards
Peptic ulcer
Defect in the mucosa of the stomach or duodenum, at least down to the basement membrane, else will be called an erosion.
What are the most common causes of peptic ulcers?
Chronic NSAID use
H. pylori infection
What are the roles of COX 1 and 2?
COX 1 produces prostaglandins for homeostatic functions everywhere incl. GI tract
COX 2 produces prostaglandins by inflamed cells and fibroblasts to mediate pain and inflammation. Releases growth factors. Produces prostacyclin to reduce leukocyte adherence and platelet aggregation
Converts arachidonic acid to PGE2
What role does COX 1 have specifically in the gut?
Inhibit gastric acid and pepsin secretion
Stimulates mucous and bicarbonate secretion
Increases mucosal blood flow - vasodilation
Reduces epithelial permeability
Inhibits cell proliferation to maintain mucosal barrier
Non-selective NSAIDs
e.g. Aspirin, Ibuprofen, Naproxen, Indomethacin
Will inhibit both COX 1 and 2
Aspirin will irreversibly inhibit these enzymes
How does COX 1 inhibition cause peptic ulceration?
Fewer prostaglandins synthesised:
Decreased mucous and bicarbonate secretion, decreased mucosal blood flow
Increased gastric acid and pepsin production
Reduction in blood flow most damaging
Epithelium is damaged by gastric acid and pepsin
Less mucous and bicarbonate produced -> cycle repeats
How may COX 2 inhibition be involved in peptic ulceration?
Increases leukocyte adhesion leads to ischaemia and release of ROS and proteases -> mucosal injury
What other mechanisms can NSAIDs cause peptic ulceration?
NSAIDs are weak acids
Become protonated when mixed with gastric acid
Enters epithelial cells, releases the H+ and is trapped
Reduces mitochondrial energy production, cell integrity, increases cell permeability -> topical irritation -> cell death -> erosions -> ulcers
How do H pylori survive in the stomach?
-Activates self cytoplasmic urease
Converts urea -> ammonia + CO2
Ammonia neutralises the gastric acid that enters the outer membrane of the bacteria.
-Release adhesins to adhere to gastric epithelial cells
How can H. pylori cause peptic ulceration?
- Release adhesins to attach to gastric endothelial cells
- Release proteases and lipases which degrade gastric mucous
- Allows gastric acid and pepsin to damage the epithelial lining
- Cause inflammatory response -> irritation -> neutrophils, lymphocytes, plasma cells and macrophages invade -> epithelial injury and death -> ulcer
What can occur if a peptic ulcer is left untreated?
Perforation of organ wall - can perforate near arteries - haemorrhaging - haemorrhagic shock
Perforation - allows bacteria into blood stream and peritoneal cavity - peritonitis and sepsis
Can narrow or occlude the gut tube if scarring and fibrosis occurs
What are the symptoms of a duodenal ulcer?
Epigastric pain - may radiate to back
Pain worse at night if duodenal
Pain often improves just after eating if duodenal
Indigestion
Bloating after eating
Nausea and vomiting
Weight gain due to improved symptoms after meal
What is the difference in symptoms between duodenal and gastric ulcers?
Duodenal - pain occurs few hours after eating when stomach is empty - may see weight gain as eating helps pain
Gastric - pain occurs from eating - may see weight loss
What type of medication are aluminium hydroxide and magnesium triscilate an example of?
Antacids
How does Aluminium Hydroxide work?
Reacts with HCl to form AlCl3 - aluminium chloride
Neutralises the stomach acid to increase pH
Inhibits action of pepsinogen by increasing pH and via adsorption
