Treatment of gastric and duodenal ulcers

Question 1

Helicobacter Pylori

Answer 1

• gram negative, motile, microaerophilic bacterium

- resides in human GI tract (exclusively colonising gastric-type epithelium)

Question 2

Ulcer formation from Helicobacter Pylori

Answer 2

• increased gastric acid formation=increased gastrin or decreased somatostatin
• gastric metaplasia=cell transformation due to excessive acid exposure
• downregulation of defence factors=decreased epidermal growth factor and decreased bicarbonate production

Question 3

Helicobacter Pylori virulence

Answer 3

UREASE

• catalyses urea into ammonium chloride and monochloramine=damages epithelial cells
• antigenic=evokes immune response
• certain virulent strains produce CagA (antigenic) or VacA (cytotoxic)=more intense tissue inflammation

Question 4

Peptic ulcer treatment

Answer 4

• antibiotics for H. Pylori

- Proton pump inhibitors

Question 5

Ulcer formation from proton pumps

Answer 5

H+/K+ ATPase

• expressed on secretory vesicles within parietal cells
• increased calcium concentration leads to increased cAMP=leads to translocation of secretory vesicles to parietal cell apical surface=leads to proton secretion

INCREASED PROTON PUMP ACTIVITY LEADS TO INCREASED PROTON SECRETION=RESULTS IN GASTRIC pH REDUCTION

Question 6

Ulcer formation from NSAIDs

Answer 6

• NSAIDs are directly cytotoxic
• reduces mucus production
• increases likelihood of bleeding
• increased acidity results in peptic ulcers

Question 7

Gastric acid regulation

Answer 7

1) Acetylcholine released from neurones (vagus/enteric) on muscarinic receptors=increased calcium concentration
2) Prostaglandins released from local cells act on EP3 receptors=decreased cAMP
3) Histamine released from enterochromaffin-like cells act on H2 receptors=decreased cAMP
4) Gastrin released from G-cells which acts on cholecystokinin B receptors (CCKB-R)=increased calcium concentration

Question 8

Gastric acid secretion

Answer 8

• increased calcium concentration and cAMP=translocation of secretory vesicles to parietal cell apical surface leading to increased proton secretion
• somatostatin=peptide that inhibits G-cells, ECL cells and parietal cells

Question 9

Antibiotics

Answer 9

Example: Amoxicillin and Clarithromycin

-removal of H. Pylori infection

Question 10

Proton pump inhibitors

Answer 10

Example: Omeprazole

-reduces acid production from parietal cells

Question 11

H2 receptor antagonist

Answer 11

Example: Ranitidine

-reduces acid production from parietal cells