L13- Peptic ulcers

Question 1

What are peptic ulcers?

Answer 1

Chronic, usually solitary lesions or sores in areas of GI tract exposed to acid/peptic juices (stomach and duodenum)
Show spontaneous relapse and remission

Question 2

What are the symptoms of a peptic ulcer?

Answer 2

• Abdominal pain (epigastric burning, nocturnal)
• Pain caused by acid (if duodenal relieved by eating, if gastric caused by eating)
• Heartburn and bloating

Question 3

What are the complications of an ulcer?

Answer 3

• Penetration into pancreas or liver
• Perforation into peritoneal cavity
• Upper GI bleeding by erosion into an artery

Question 4

What do parietal and chief cells do?

Answer 4

• Chief cells produce pepsinogens which are converted to pepsins in protein digestion
• Parietal cells release strong HCl digestive agent and disinfectant

Question 5

What does HCl do?

Answer 5

• Damages cells lining stomach and duodenum so surface and mucus neck cells form a protective mucus layer

Question 6

What factors cause peptic ulcers to develop?

Answer 6

• Smoking (reduce healing)
• H. pylori (weaken mucosal defence)
• Aspirin and other NSAIDs (block PGs- weaken mucosal defence)
• Stress

Question 7

What is the main cause of gastric and duodenal ulcers?

Answer 7

• Gastric- infection with H. pylori of gastric corpus, NSAIDs
• Duodenal- H. pylori infection of gastric antrum, increased secretion of acid results in gastric metaplasia in duodenum which can be infected by H. pylori

Question 8

How does H. pylori cause cancer?

Answer 8

• Long term effect

* Gastric glandular cells replaced by intestinal and fibrous tissue

Question 9

How does H. pylori protect itself?

Answer 9

Secretes urease which converts urea to ammonia and CO2 (raises pH, acid buffer) to protect itself from the acid

Question 10

What is the mechanism of gastric acid secretion by parietal cells?

Answer 10

• H+ generated in the parietal cell from dissociation of water
• OH- ions formed combine with CO2 to form HCO3-
• HCO3- transported out of basolateral membrane in exchange for Cl-.
• H+ is pumped out of the cell, into the lumen, in exchange for K+ through the action of the proton pump
• H+ and Cl- combine to give HCl

Question 11

How is gastric acid secretion by parietal cells regulated?

Answer 11

• Histamine released from Ecl in stomach lining acts on H2 receptors on parietal cell
• cAMP is produced which phosphorylates the proton pump via PKA and causes its upregulation

Question 12

What stimulates the release of histamine?

Answer 12

• Gastrin from G cells
• Ach from parasymp nerves
Also work directly on parietal cells by stimulating Ca2+ release to release acid

Question 13

How is acid release inhibited?

Answer 13

• PGE2 acts on EP receptors on parietal cells and inhibits proton pump
• Also stimulates mucous secretory cells to secrete mucus
• Increases blood flow to dilute acid carried and prevent build up by vasodilating

Question 14

What are drug treatments for peptic ulcers?

Answer 14

• Proton pump inhibitors
• H2 receptor blockers
• Drugs enhancing mucosal protection
• Antacids
• Antimicrobial therapy

Question 15

What are proton pump inhibitors?

Answer 15

OMEPRAZOLE, ESOMEPRAZOLE
• Irreversibly block H+/K+ ATPase
• Inactive prodrugs at neutral pH
• React covalently with sulphydryl groups on proton pump
• 1st line drugs

Question 16

What are H2 receptor blockers?

Answer 16

FAMOTIDINE, RANITIDINE, CIMETIDINE
• Selectively block parietal cell H2 receptors
• Withdrawn due to contamination with NDMA (potential carcinogen)

Question 17

What are drugs enhancing mucosal production?

Answer 17

• BISMUTH CHELATE- coats ulcer and protects to promote healing, stimulates mucus
• SUCRALFATE- AlOH and sulphated sucrose complex, mainly used for stress caused duodenal ulcers, buffers acid and stimulates mucus

Question 18

What are antacids?

Answer 18

NaHCO3, MgHCO3, AlOH3
• Neutralise gastric acid and inhibit pepsin action
• Used while waiting for PPI/H2 blocker to kick in
• NaHCO3 may cause systemic alkalosis

Question 19

What is misoprostil?

Answer 19

• A stable PGE1 analogue which heals and prevents NSAID induced damage when taken with NSAID
• PG’s are important in maintaining integrity of gastric mucosa, NSAIDs inhibit their synthesis

Question 20

What is antimicrobial therapy?

Answer 20

CLARITHROMYCIN, AMOXICILLIN, OMEPRAZOLE
• Eradicate H. pylori and prevent return
• Combined with H2 blocker or omeprazole
• Combining drugs reduces possibility of bacterial resistance by mutation as each drug has a different mechanism of action