30 - Treatment of Gastric and Duodenal Ulcers

Question 1

Outline how helicobacter pylori can cause a peptic ulcer

Answer 1

HELICOBACTER PYLORI (H PYLORI)

Overall:

Dissolves mucus layer - no protection of gastric antrum epithelial cells

Causes epithelial cell death

Increased activity leads to the peptic ulcer

Specifically:

Increased gastric acid formation

• Increased gastrin or decreased somatostatin
• Shifts the balance towards gastric acid formation

Gastric metaplasia

• Cell transformation due to excessive acid exposure

Downregulation of defence factors

• Decreased epidermal growth factor
• Decreased bicarbonate production

Virulence:

Urease

• catalyses urea into ammonium chloride and monochloramine
• ammonium chloride is toxic
• damages epithelial cells

Urease

• antigenic
• detected by our immune cells
• evokes immune response

Certain virulent strains produce CaqA (antigenic) or VacA (cytotoxic)

• leads to more intense tissue inflammation
• normally, it is commensal but those mentioned above are the virulent strains due to the proteins they produce

Question 2

How would you treat an uncomplicated peptic ulcer caused by helicobacter pylori?

Answer 2

ANTIBIOTICS (for H. pylori infection)

Amoxicillin & Clarithromycine/Metronidazole

PROTON PUMP INHIBITOR (PPI)

​Reduces acid production

Question 3

How would a peptic ulcer caused by helicobacter pylori present?

Answer 3

Epigastric pain

Burning sensation that occurs after meals (1-2 hours after food)

Question 4

Outline the investigastions and diagnosis that would occur surrounding helicobacter pylori for a peptic ulcer

Answer 4

CARBON-UREA BREATH TEST

• looks for urea in the breath
• POSITIVE

STOOL ANTIGEN TEST

• looks for h. pylori antigen in stool
• POSITIVE

Leads to a H. pylori positive peptic ulcer diagnosis

Question 5

Outline facts about Helicobacter Pylori

Answer 5

Gram Negative

Motile (via flagella)

Microaerophilic bacterium

Resides in human GI tract as a commensal

• exclusively gastric-type epithelium

Spiral shape

Question 6

What is the role of proton pumps in the stomach?

Answer 6

PROTON PUMPS (H⁺-K⁺-ATPase pumps)

Expressed on secretory vesicles within parietal cells (also where h. pylori also resided)

Not normally expressed on the apical membranes of parietal cells, it is in vesicles

These vesicles are activated by either:

• Increased intracellular calcium concentration
• Increased cAMP

Translocation of secretory vesicles to parietal cell apical surface

Increased proton secretion (hydrogen removed) and potassium brought into cell

Question 7

How can proton pumps in the stomach play a role in the development of peptic ulcers?

Answer 7

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

Question 8

How can NSAIDs cause peptic ulcers?

Answer 8

NSAIDs

​Directly cytotoxic

Reduces mucus production

Increases likelihood of bleeding

Increased acidity then leads to peptic ulcer

Question 9

Outline the investigations and diagnosis that would occur around peptic ulcers due to NSAIDs

Answer 9

CARBON-UREA BREATH TEST

• negative

STOOL ANTIGEN TEST

• negative

Therefore, it has not been caused by h. pylori.

NSAID USE

• positive

Question 10

How would a peptic ulcer due to NSAIDs use present?

Answer 10

Epigastric pain

Burning sensation

Question 11

How would you treat a peptic ulcer due to NSAIDs?

Answer 11

Removal of NSAID (e.g. aspirin)

Proton Pump Inhibitor (PPI, omeprazole) or Histamine H₂ Receptor Antagonist (Rantidine)

• 4-8 weeks
• H₂ receptor increases acid secretion

Question 12

How is gastric acid regulated in the stomach?

Answer 12

GASTRIC ACID REGULATION - 4 receptor types

1. ACh released from neurones (vagus/enteric) acts on muscarinic (M₃) receptors. Leads to increased intracellular calcium concentration
2. Prostaglandins (PGs) released from local cells act on EP₃ receptors. Leads to increased cAMP
3. Histamine released from enterochromaffin-like cells (ECL) act on H₂ receptors. Leads to increased cAMP
4. Gastrin released from bloodstream acts of cholecystokinin B receptors. Leads to increased intracellular calcium concentration

Any of these 4 lead to an increase in calcium or cAMP. This means there will be more expression of proton pumps, and a resulting increase in gastric acid secretion.

Question 13

How is gastric acid secreted in the stomach?

Answer 13

1. Increased intracellular calcium and increased cAMP
2. Leads to translocation of secretory vesicles to parietal cell apical surface
3. H+ secretion

Question 14

What does the term ‘peptic ulcer’ refer to?

Answer 14

Gastric and duodenal ulcers

Question 15

Why is the carbon-urea breath test used to check for a h.pylori infection?

Answer 15

H. Pylori produces the urease enzyme

Question 16

If a peptic ulcer presents with a constant burning sensation, instead of just after food, what does this suggest?

Answer 16

If the burning sensation is constant, it suggests that is a complicated peptic ulcer rather than uncomplicated

The situation is more advanced

Question 17

How would you change the antibiotic treatment for a peptic ulcer due to h. pylori infection if it went from uncomplicated to complicated?

Answer 17

UNCOMPLICATED

Amoxicillin & Clarithromycine/Metronidazole (2 antibiotics)

COMPLICATED

Amoxicillin & Clarithromycine/Metronidazole

Also, consider Quinolone, Tetracycline

(4 antibiotics)

Question 18

How would you treat a complicated peptic ulcer due to h. pylori infection?

Answer 18

Amoxicillin & Clarithromycine/Metronidazole

Consider Quinolone, Tetracycline

Proton Pump Inhibitor (omeprazole: 4-12 weeks)