Gastric Acid Secretion Disorders Flashcards
What is the mechanism of peptic ulcer formation?
Breakage of mucosal barrier creates an imbalance between protective and damaging factors which can cause peptic ulcers
Hay exposure of tissues to the erosive effects of HCl and pepsin
What are the protective factors that prevent autodigestion of the stomach by pepsin?
Secretion of alkaline mucus and HCO3-
Presence of tight junctions between the epithelial cells lining the stomach and fibrin coat
Replacement of damaged cells within the gastric pits
Prostaglandins (E2 and prostacyclin I2): inhibit acid secretion, enhance blood flow and mucus secretion
How do NSAIDs (e.g. aspirin) play a role in gastric acid secretion disorders?
Causes topical gut irritation(don’t take on empty stomach)
Impairs the barrier properties of mucosa
Suppresses protective PG synthesis by inhibiting cyclooxygenase
↓ gastric mucosal blood flow
Interferes w superficial injury repair by inhibiting TXA2 and thus platelet aggregation
H. Pylori is the commonest cause of peptic ulcer. What are its virulence factors?
Corkscrew motility: Uses its flagella to move close to the epithelium Has mucinase activity which breaks down mucus Produces urease (converts urea to ammonia, which buffers gastric acid and produces C02). The ammonia also damages the gastric mucosa
H. pylori infection dysregulates gastrin secretion → ↑gastrin secretion
CagA. This disrupts cell junctions, affect cell proliferation/differentiation, and induces inflammation.
VacA: makes vacuoles, induces apoptosis and inflammation. It allows H. pylori to live in macrophages, and inhibits T-cell production by decreasing IL-2 production
Give the aggravators of peptic ulcer
Regurgitated bile acids
NSAIDs
Genetics
Smoking, alcohol, spicy foods
Chronic gastritis
H. pylori infection
Where are peptic ulcers common?
First part of the duodenal cap
Junction of antrum and body
Distal oesophagus, especially in Barrett’s oesophagus
Meckel’s diverticulum (congential abnormal pouch in the intestine)
After gastroenterostomy
How would investigate a suspected peptic ulcer?
Low dose PPI (omeprazole)
Endoscopy
Histological examination and staining of an EGD biopsy
Test for H. pylori using stool antigen test
Evaluate urease activity using urea breath test:
Take 14C- or 13C-labelled urea tablet
Measure CO2 in exhaled breath before and 10-30 mins after dosing
Describe the clinical presentation of a peptic ulcer
What are the complications of peptic ulcer?
Perforation (peritonitis) and penetration (liver and pancreas may be affected); leakage of luminal contents
Narrowing of pyloric canal (stricture causing acquired pyloric stenosis in the stomach) or oesophageal stricture
Malignant change becomes 3-6 times likely with H. pylori infection
What type of drug acting on H2 receptors is used to treat peptic ulcers and how do they work?
H2 receptor antagonists (cimetidine or ranitidine)
Inhibit histamine action at H2 receptors on parietal cells
Reduce gastric acid secretion and as a consequence reduce pepsin secretion (bc conversion of pepsinogen to pepsin needs hyperacidity)
Act on ECLs to inhibit histamine-, ACh- and gastrin-stimulated acid secretion
Can decrease basal and food-stimulated acid secretion
What are the side effects of H2 receptors?
Generally rare; diarrhoea, muscle cramps, transient rashes, hypergastrinaemia- can make the condition worse
Cimetidine → gynaecomastia in men (↓ sexual function)
Cimetidine also inhibits P450 enzymes → ↓ metabolism of a number of drugs metabolised by P450 enzymes, e.g. anticoagulants, tricyclic antidepressants, so using these drugs together could cause bleeding
What is the difference between cimetidine and ranitidine?
IC50 for ranitidine = 0.07mcg/ml
IC50 for cimetidine = 0.44mcg/ml
The lower the IC50, the more active the drug
Ranitidine is therefore more potent- less of it is needed to produce the same effect
Give examples of proton pump inhibitors and what they treat
Examples: omeprazole, lanzoprazole, pantoprazole
Used to treat: peptic ulcer, reflux oesophagitis; partial therapy for H. pylori
Can also be used in the treatment of Zollinger-Ellison syndrome
What is the mechanism of action, as well as side effects of proton pump inhibitors?
Weak bases; inactive at neutral pH and irreversibly inhibit the H+/K+-ATPase pump which usually pumps H+ out of parietal cells into the lumen in exch for potassium.
This decreases basal and food-stimulated gastric acid secretion
Unwanted effects: Headache, diarrhoea, confusion, rashes, gynaecomastia, dizziness
What are the ways in which H.pylori is treated?
Combination therapy is the way forward: Omeprazole, amoxicillin and metronidazole
Some cytoprotective drugs protect the gastric mucosa eg bismuth chelate:
Provide a physical barrier over the surface of the ulcer
Enhances local synthesis of PGs
Promote bicarbonate secretion and adsorbs pepsin
Bismuth chelate prevents adherence of H. pylori to the mucosa or inhibit its proteolytic activity
