Peptic ulcers

Question 1

What are the two types of peptic ulcer?

Answer 1

Gastric ulcer

Duodenal ulcer

Question 2

Describe the basic patient presentation of a H pylori positive peptic ulcer

Answer 2

Epigastric pain, burning sensation that occurs after meals

Question 3

State the two common investigations to be carried out to confirm the presence of H pylori positive peptic ulcer

Answer 3

Carbon-urea breath test 
Stool antigen (urease) test

Question 4

Briefly describe what Helicobacter pylori (H pylori) does to cause ulceration

Answer 4

• Dissolves mucus layer in small portions of stomach
• Causes epithelial cell death
• in the presence of increased acidity => peptic ulcer

Question 5

What can happen in severe stomach ulceration?

Answer 5

Bleeding from stomach area

Question 6

What are some important characteristics of H pylori?

Answer 6

• Gram negative
• motile
• microaerophilic bacterium
  Resides in human GI tract (normally as a commensal bacteria) – exclusively colonising gastric-type epithelium

Question 7

How does H pylori increase gastric acid production?

Answer 7

Increases production gastrin
or
Decreases production of somatostatin

Question 8

Excessive acid exposure to the epithelial cells results in what

Answer 8

Gastric metaplasia – cell transformation

Question 9

Describe an additional form of attack on the epithelial cells by the H pylori

Answer 9

Downregulation of defence factors:

decreased epidermal growth factor & decreased bicarbonate production

Question 10

What enzyme is produced by H pylori that is important to its virulence? How?

Answer 10

Urease

• can damage epithelial cells directly
• catalyses urea into ammonium chloride & monochloramine which damage epithelial cells

Also, urease is antigenic and so evokes an immune response thus leading to further damage

Question 11

Certain virulent strains of H pylori can also produce what toxins? What do these do?

Answer 11

Certain virulent strains produce CagA (antigenic) or VacA (cytotoxic) => more intense tissue inflammation

Question 12

Describe the treatment of a H pylori positive peptic ulcer

Answer 12

TRIPLE THERAPY
2 Antibiotics:
Amoxicillin & Clarithromycin/Metronidazole

Proton Pump Inhibitor (PPI) to reduce acid production (for 7 days) e.g. omeprazole

Question 13

How might the treatment H pylori positive peptic ulceration differ in the chronic disease state?

Answer 13

• Consider quinolone, tetracycline
• Proton Pump Inhibitor (omeprazole) – 4-12 weeks
• Use cytoprotective drugs which enhance mucosal protection and/or build a physical barrier over the ulcer e.g. Sucralfate, Bismuth chelate / Pepto-Bismol

Question 14

Briefly describe where the proton pumps come from and what function they carry out

Answer 14

Proton pumps are expressed on secretory vesicles within parietal cells
Increased intracellular [Ca2+] and an increased cAMP concentration => translocation of secretory vesicles to parietal cell apical surface
Proton pumps actively send H+ into the stomach in exchange for K+ => increased acidity of gastric secretions

Question 15

If a patient presents with epigastric pain and burning sensation, but both H pylori tests came back as negative what would you suspect as the cause? Why?

Answer 15

NSAID use

• Directly cytotoxic
• Reduces mucus production
• Increases likelihood of bleeding
• Increases acidity

Question 16

Describe the treatment of peptic ulcer caused by NSAID use.

Answer 16

• Removal of NSAID (if possible)
• Proton Pump Inhibitor
• Histamine H2 receptor antagonist (Ranitidine) for 4-8 weeks

Question 17

What 4 molecules/chemicals are involved in gastric acid regulation? Describe how for each.

Answer 17

1. Acetylcholine (ACh) released from neurones (vagus/enteric) acts on muscarinic (M3) receptors => increased [Ca2+]i
2. Prostaglandins (PGs) released from local cells act on EP3 receptors => decreased cAMP (so protective effect)
3. Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors - increased cAMP
4. Gastrin released from G-cells, acts on cholecystokinin B receptors - increased [Ca2+]i

Question 18

How does somatostatin reduce the acidity of gastric secretion?

Answer 18

Inhibits G-cells, ECL cells and parietal cells