Acid Secretion

Question 1

What are the defences of the gastric mucosa?

Answer 1

Integrity of the epithelium, the mucous membrane barrier (which generates a pH gradient), the high rate of cell replication and good vascular supply

Question 2

What cells secrete acid? How?

Answer 2

Parietal cells secrete hydrochloric acid at a pH of 0.8 – it is secreted into canaliculi which are continuous with the stomach lumen.

They have receptors on the basolateral membrane which stimulate acid secretion (gastrin receptors, histamine receptors and acetylcholine receptors), and acid production is via a proton pump, which exchanges protons for potassium – it needs to be phosphorylated to be active.

The parietal cell can be resting or active (this is why PPIs need to be given regularly not PRN as they only bind active pumps)

Question 3

PPI MOA

Answer 3

PPIs target the HK ATPase. They are given as prodrugs which are activated by the low pH in the stomach, which then bind covalently to cysteines on the ATPase.

Bind to active proton pumps and irreversibly destroy.

Because they only act on active pumps they reach maximal efficacy over 2-3 days – restoration of acid synthesis requires de novo synthesis of the ATPases

Question 4

Examples, ADRs of PPI

Answer 4

o	Omeprazole
o	Lansoprazole
o	Rabeprazole
o	Pantoprazole
o	Esomeprazole

• Constipation
• Diarrhoea
• Flatulence
• Headaches
• Abdominal pain
• Nausea and vomiting

Question 5

MOA of H2 antagonist

Answer 5

H2 antagonists antagonise the histamine receptors which reduces acid secretion from the parietal cells – they don’t bind irreversibly. You give them twice daily.

Question 6

Examples, ADRs of H2 antagonist

Answer 6

o Cimetidine
o Ranitidine

• Diarrhoea
• Headache
• Tiredness
• Dizziness
• Rash

Question 7

What are antacids?

Answer 7

Aluminium hydroxide, Gaviscon

Neutralise stomach acid - not long term relief

ADRs - contipation

Question 8

What is conservative management for GORD?

Answer 8

Don't ear late at night
Tilt bed up slightly
Less alcohol
Antacid for symptoms
H2A/PPI for cause

Question 9

How do you treat peptic ulcers?

Answer 9

Stop NSAIDs
6 weeks of H2A/PPI
Helicobacter pylori eradication - amoxicillin/clarythromicin and a PPI

Question 10

How do you treat H. pylori infection

Answer 10

• Acid suppression (PPIs)
• 2 antibiotics
o Amoxicillin
o Clarithromycin

Question 11

What commonly occurs with DU and GU?

Answer 11

Helicobacter pylori infection - as infection in the antrum leads to increases in acid secretion hence ulceration