Gastric acid secretion disorders Flashcards
What are the mechanisms of peptic ulcer formation?
- Breakage of mucosal barrier – imbalance between protective and
damaging factors - Exposure of tissues to the erosive effects of HCl and pepsin
What are the sites affected by peptic ulcers?
Oesophagus
stomach
duodenum
What are factors pre-disposing to peptic ulceration?
-H.pylori
-Smoking
-Stress
-NSAIDs
What are protective factors that prevent autodigestion of the stomach?
- Secretion of alkaline mucus and HCO3-
- Protein content of food
- Presence of tight junction between the epithelial cells lining the stomach
and fibrin coat - Replacement of damaged cells within the gastric pits
- Prostaglandins (E and I): inhibit acid secretion and enhance blood flow
What does mucus layer protect in the stomach?
Mucus layer protects the gastric mucosa
from the low pH of the gastric juice
How do NSAIDs play a role in gastric acid secretion disorders?
Aspirin blocks the synthesis of PGE2 and TXA2
What synthesis do NSAIDs suppress?
-Suppresses gastric prostaglandin synthesis
What do NSAIDs decrease flow of?
↓ gastric mucosal blood flow
What do NSAIDs inhibit in stomach?
Inhibit platelet aggregation
What do NSAIDs interfere with?
Interferes with the haemostasis process
What gram is H.pylori?
Gram negative
What shape is H.pylori?
Spiral shaped; can be coccoid too
What does H.pylori penetrate?
Penetrates gastric mucosa (able to survive
under the harsh condition of the stomach
What does the flagella of h.pylori enable?
The flagella enable its
‘corkscrew’ motility towards
the gut epithelium
What is a peptic ulcer?
ulcer in the digestive tract (in the
stomach or duodenum)
What virulence activity does h.pylori have?
Mucinase activity
What does H.pylori produce and what does this do to gastric acid and what does this produce?
Produces urease (converts urea to ammonia, which buffers gastric acid
and produces CO2)
What does cytotoxin-associated antigen(CagA) in H.pylori insert?
inserts pathogenicity islands and
confers ulcer-forming potential
What does vacuolating toxin A in h.pylori alter?
alters the trafficking of intracellular protein
in gastric cells
What is the commonest cause of peptic ulcers?
H.pylori
What does H.pylori infection dysregulate?
H.pylori infection dysregulates gastrin secretion → ↑gastrin secretion
What is the mechanism of H.pylori in mucosal damage?
1, H.pylori moves with corkscrew motility and attaches to gastric epithelial cells
2. This h.pylori relesases urease which forms NH3 to neutralise gastric acid.
3. This allows more h.pylori to colonise the gastric epithelial cells
4. Bacterial mucinase then causes mucosal damage
5. Mucosal cell death occurs due to cytotoxins and ammonia
What is the common cause of mucosal damage and ulceration caused by both H.pylori and NSAIDs?
-Hydrogen ions
-Pepsin
Where are peptic ulcers common in the duodenal cap?
first part of the duodenal cap
Where are peptic ulcers common in in the stomach?
junction of antrum and body
What are diagnostic tests for peptic ulcers?
- Low dose PPI(Omeprazole)
- Endoscopy
- Histological examination and staining of an EGD biopsy
What is a test for the presence of H.pylori?
- Stool antigen test
- Evaluate urease activity through urea breath test
What are the steps involved in urea breath test?
- Take 14C or 13C labelled urea tablet
- There is H14CO3- bicarbonate in bloodstream which comes out as 14CO2 in breath
- You then collect 2L breath in mylar balloon
- Then transfer CO2 to counting vial
- Add 10ml scintillation fluid
- Scintillation counter will give total count
What aer clinical symptoms of peptic ulcers?
- Nausea
- Anorexia
- Vomiting
- Epigastric pain
- Chest discomfort/weight loss
- Black, tarry stools
Where does chronic peptic ulcer occur?
Occurs in upper GIT (pepsin and HCl)
Where does acute peptic ulcer develop?
Develops from areas of corrosive gastritis (oesophagus, stomach,
proximal duodenum), severe stress or shock (burns, trauma)
What happens to surface epithelium by acute peptic ulcer?
Acute hypoxia of surface epithelium
What are the outcomes of peptic ulcers?
- Severe bleeding
- Heal with no scarring
- Chronic peptic ulcer
What are complications of peptic ulcer?
- Haemorrhage (GI bleeding)
- 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
What are examples of H2 receptor antagonists?
Cimetidine
Famotidine
Nizartidine
What are clinical uses of H2 receptor antagonists?
- Peptic ulcer
- Reflex oesophagitis
What is the mechanism of action of H2 receptor antagonists?
-Inhibit histamine action at H2 receptors on parietal cells
* Reduce gastric acid secretion and as a consequence reduce pepsin
secretion – do you know how it does that?
* Inhibit histamine-, ACh- and gastrin-stimulated acid secretion
What are unwanted effects of H2 receptor antagonists?
diarrhoea, muscle cramps, transient rashes,
hypergastrinaemia
What effect can cimetidine bring in men?
Cimetidine → gynaecomastia in men
What enzymes may cimetidine inhibit and what may that cause?
Cimetidine also inhibits P450 enzymes → ↓ metabolism of a number of
drugs metabolised by P450 enzymes, e.g. anticoagulants, tricyclic
antidepressants (e.g. imipramine, dosulepin, amytriptyline, etc.)
What are examples of proton pump inhibitors?
omeprazole, lanzoprazole, pantoprazole, rabeprazole
What are the clinical uses of proton pump inhibitors?
-Peptic ulcer
-Reflux oesophagitis
-Zollinger-Ellison syndrome
What is the mechanism of action of proton pump inhibitors?
- Weak bases; inactive at neutral pH and irreversibly inhibit the H+/K+-
ATPase pump - Decreases basal and food-stimulated gastric acid secretion
What are unwanted effects of proton pump inhibitors?
Headache, diarrhoea, mental confusion, rashes, somnolence, impotence,
gynaecomastia; dizziness
What are the combination therapies for H.pylori infection?
- Omeprazole, amoxicillin and metronidazole
- Omeprazole, clarythromycin and amoxicillin or tetracycline, metronidazole and
bismuth chelates - Lansoprazole, clarithromycin, tinidazole and bismuth chelates
What is an example of a drug that protects the gastric mucosa?
Bismuth chelate
What does bismuth chelate provide?
Provide a physical barrier (coat) over the surface/base of the ulcer
What does bismuth chelate enhance local synthesis of?
Enhances local synthesis of PGs
What does bismuth chelate promote secretion of?
Promote bicarbonate secretion
What are the side effects of bismuth chelate?
-Nausea
-Vomiting
-Blackening of tongue and faeces
What can bismuth chelate do to patients with renal impairments?
May rise causing encephalopathy
What type of reaction do we get if metronidazole is taken with alcohol and how will patient feel?
Disulfiram-like reaction
-Patient will feel severely ill
What does disulfiram inhibit and what deos this cause?
Disulfiram inhibits acetaldehyde dehydrogenase, build up of
acetaldehyde → unpleasant flushing and nausea & headache
When do you not give metronidazole to pregnant women?
First trimester
What are examples of drugs that protect the gastric mucosa?
Prostanoids
-PGE2
-PGI2
-TXA2
What is misoprostol?
Misoprostol (a synthetic analogue of PGE1)
