Treatment of peptic ulcers

Question 1

Recall the 2 main presenting features of a peptic ulcer

Answer 1

1. Epigastric pain 2. Burning sensation

Question 2

Recall the 3 investigations done for peptic ulcers, and which of these is the gold standard

Answer 2

Gold standard = endoscopy

Both Carbon urea breath test and Stool-antigen test for H pylori will be positive for H pylori, but negative for NSAID induced peptic ulcer

Question 3

Describe the basis of a carbon urea breath test and the implication of a positive result

Answer 3

Give patient loads of unique carbon isotope-urea and if you get increased levels of specific-isotope CO2 being exhaled = positive for H pylori

Question 4

How can the history differentiate between a complicated and uncomplicated H.pylori positive peptic ulcer?

Answer 4

Pain after meal times = •H Pylori positive uncomplicated peptic ulcer whereas if meal pain is constant and not just after mal = h.pylori postive complicated peptic ulcer.

Question 5

`What is the most common cause of peptic ulcer?

Answer 5

Bacterial infection with H Pylori

Question 6

In around what % of the population is H pylori commensal?

Answer 6

50%

Question 7

How does H pylori infection cause development of a peptic ulcer?

Answer 7

1. It produces urease which can break down the protective mucous layer 2. It releases exotoxins at the epithelium, leading to IL8 release and local inflammation.

Increased gastrin production leads to increased acid production

Question 8

How do NSAIDS cause development of peptic ulcers?

Answer 8

Directly cytotoxic, reducing mucous production and causing IL8 release at epithelium,

• Increases likelihood of bleeding
• Increased acidity à peptic ulcer

Question 9

What is the first line treatment for uncomplicated H pylori + peptic ulcers?

Answer 9

Amoxycillin combined with Clarithromycin/ metronidazole, and a PPI for 7-14 days

Question 10

Describe the treatmentfor a complicated h.pylori postive peptic ulcer?

Answer 10

1. Amoxycillin, clarithromycin/metronidazole given together with quinolone 2. Bismuth 3. Omeprazole (PPI) for 4-12 weeks

Question 11

How do PPIs reduce gastric acid secretion?

Answer 11

Inhibit proton pump on apical side of parietal cells

Question 12

If NSAID cannot be removed, how is an NSAID-induced peptic ulcer treated?

Answer 12

PPI or H2 antagonist

Question 13

Why would an H2 receptor antagonist be useful in peptic ulcer treatment?

Answer 13

H2 receptors on parietal cells stimulate proton pump to increase acid secretion

Question 14

Recall the function of prostaglandins in the stomach

Answer 14

PROTECTIVE 1. Increase blood supply to stimulate mucous production 2. Increase HCO3- production 3. Decrease acid production

Question 15

Recall the risk factors for peptic ulcers

Answer 15

1. Stress 2. genetic 3. Lifestyle (diet/ alcohol/ smoking)

Question 16

Recall 3 molecules that inhibit gastric acid production

Answer 16

1. Secretin 2. GIP 3. Somatostatin

Question 17

Give an example of a histamine antagonist used in peptic ulcer therapy

Answer 17

Ranitidine

Question 18

How do H+-K+-ATPase (proton pumps) work, and how these lead to ulcer formation

Answer 18

• Expressed on secretory vesicles within parietal cells
• ­ increased [Ca2+] ® increased ­cAMP ® translocation of secretory vesicles to parietal cell apical surface ® H+ secretion

Ulcer formation

•Increased activity of proton pump – increased­ H+ secretion ® reduction gastric pH

Question 19

Explain how gastric acid is regulated

Answer 19

Gastric acid regulation

1. Acetylcholine (ACh) released from neurones (vagus / enteric) acts on muscarinic (M3) receptors -tf increasing ­ [Ca2+]i
2. Prostaglandins (PGs) released from local cells act on EP3 receptors - tf increasing ­cAMP
3. Histamine released from enterochromaffin-like cells (ECL) act on H2 receptors - tf increasing ­cAMP
4. Gastrin released from blood stream acts on cholecystokinin B receptors - tf increasing ­ [Ca2+]

Gastric acid secretion

•Raised­ [Ca2+] & ­cAMP ® translocation of secretory vesicles to parietal cell apical surface ® H+ secretion

Question 20

how to treat NSAID-induced peptic ulcers

Answer 20

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