Peptic Ulcers

Question 1

How do peptic ulcers present

Answer 1

Epigastric pain

Burning sensation that occurs after meals

Question 2

What investigations should be done in suspected H. Pylori peptic ulcers and what will the results be if they are present

Answer 2

Carbon-urea breath test – positive

Stool antigen test – positive

Question 3

Describe the pathophysiology of H pylori peptic ulcers

Answer 3

Helicobacter pylori (H pylori)
Dissolves mucus layer
Causes epithelial cell death
Increased acidity -> peptic ulcer

Question 4

Describe helicobacter pylori

Answer 4

Gram negative, motile, microaerophilic bacterium

Resides in human GI tract – exclusively colonising gastric-type epithelium

Question 5

Explain how H. Pylori causes ulcer formation

Answer 5

Increased gastric acid formation – increased gastrin or decreased somatostatin

Gastric metaplasia – cell transformation due to excessive acid exposure

Downregulation of defence factors - decrease epidermal growth factor and bicarbonate production

Question 6

Describe the virulence of H Pylori

Answer 6

Urease (enzyme)

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

Question 7

What are the effects of urease

Answer 7

Catalyses urea into ammonium chloride + monochloramine, which damages epithelial cells

Antigenic and evokes immune response

Question 8

What is the treatment for a H pylori positive peptic ulcer

Answer 8

Amoxicillin + Clarithromycin/Metronidazole – Antibiotics

Proton Pump Inhibitor (PPI) – reduces acid production

Question 9

Describe the proton pumps found in the stomach and how they work

Answer 9

H+-K-ATPase
Expressed on secretory vesicles within parietal cells
1. Increased calcium
2. Increased cAMP
3. translocation of secretory vesicles to parietal cell apical surface
4. H+ secretion

Question 10

Explain how proton pumps are involved in ulcer formation

Answer 10

1. Increased activity of proton pump
2. H+ secretion
3. reduction gastric pH

Question 11

What are the investigations done for suspected peptic ulcers due to NSAID use

Answer 11

Carbon-urea breath test – negative
Stool antigen test – negative
NSAID use – positive

Question 12

Describe the pathophysiology of peptic ulcers due to NSAIDs

Answer 12

Directly cytotoxic
Reduces mucus production
Increases likelihood of bleeding
Increased acidity -> peptic ulcer

Question 13

What is the treatment for NSAID peptic ulcers

Answer 13

Removal of NSAID
Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks
H2 receptor increases acid secretion

Question 14

Which molecules are involved in gastric acid regulation

Answer 14

Acetylcholine
Prostaglandins
Histamine
Gastrin

Question 15

Describe the role of acetylcholine in gastric acid regulation

Answer 15

Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors
Increasing [Ca2+]i

Question 16

Describe the role of prostaglandins in gastric acid regulation

Answer 16

Prostaglandins (PGs) released from local cells act on EP3 receptors
↓ cAMP

Question 17

Describe the role of histamine in gastrin regulation

Answer 17

Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors
Increased cAMP

Question 18

Describe the role of gastrin in gastric acid regulation

Answer 18

Gastrin released from G-cells, acts on cholecystokinin B receptors
Increased [Ca2+]i

Question 19

What is somatostatin

Answer 19

peptide that inhibits G-cells, ECL cells and parietal cells

Question 20

Why is combination treatment the best practice

Answer 20

Eliminates bacterial infection whilst also decreasing hydrogen produced from the parietal cells of the stomach