Treatment of Gastric and Duodenal Ulcers

Question 1

What is a peptic ulcer?

Answer 1

an area of damage to the inner lining of the stomach (gastric ulcer) or the upper part of the duodenum (duodenal ulcer)

Question 2

How can you distinguish between peptic and duodenal ulcers?

Answer 2

Gastric ulcer – pain at mealtimes when the acid is secreted

Duodenal ulcer – pain relieved by a meal as the pyloric sphincter closes (pain starts after 2-3 hours)

Question 3

How can you investigate peptic ulcers?

Answer 3

Carbon-urea breath test – positive

• Involves giving the patient a lot of urea – H. pylori metabolises urea to nitrogen
• If you get increased levels of nitrogen, this means the H. pylori infection is present -> POSITIVE

Stool antigen test – positive
-This involves testing for H. pylori antigens within the stool of the patient

Question 4

How does H. pylori cause peptic ulcers?

Answer 4

A mucus layer protects the stomach epithelium from the acidic environment

• H. pylori can dissolve our mucus layer using urease enzyme: this allows H. pylori to access epithelia
• causes epithelial cell death: H. pylori releases exotoxins -> increased inflammatory reaction
• Eventually, there is damage to the mucus layer, epithelial layer, and then TO THE INTERSTITIAL LAYER -> ulceration within the region of damage
• Increased acidity -> peptic ulcer
• There is also a shift in balance of certain cell types in the stomach
• You get more cells that produce protons, which causes an INCREASED ACIDITY -> further ulceration

Question 5

How do you treat H. pylori positive uncomplicated peptic ulcers?

Answer 5

1. Amoxicillin & Clarithromycin/Metronidazole – Antibiotics to treat H. pylori infection
   - The two drug combination (i.e. amoxicillin + clarithromycin/metronidazole) is very effective
   - Once the H. pylori infection is removed, the stomach is amazing at healing itself
2. Proton Pump Inhibitor (PPI) – reduces acid production, given for 7 days

Question 6

How do you treat H. pylori complicated peptic ulcers?

Answer 6

Antibiotics for H Pylori (amoxicillin & clarithromycin/metronidazole)

• All 3 can be given in the case of an individual with recurrent peptic ulcers
• Consider adding quinolone or tetracycline
• These antibiotics may be added alongside the first line antibiotics
• Proton Pump Inhibitor (omeprazole) – 4-12 weeks

Question 7

How does a PPI treat peptic ulcers?

Answer 7

• Parietal cells produce hydrogen ions via the proton pumps
• The main regulators are the cholinergic system and the histaminergic system in the stomach - Acid is produced by the H+/K+ exchanger -> Histamine then acts on H2 receptors on parietal cells to trigger activation of these exchangers via a cAMP-pathway

PPI - irreversible inhibitor of the H+/K+ ATPase exchanger

Question 8

What is the pathophysiology of NSAID use peptic ulcers?

Answer 8

• The NSAID can be directly cytotoxic

- NSAIDs also reduce mucus production

Question 9

How do you treat peptic ulcers that have arisen from NSAID use?

Answer 9

• Removal of NSAID drugs – you can’t always do this (e.g. in individuals with other co-morbidities)
• Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks

Question 10

How is gastric acid regulated?

Answer 10

1. ACh released from vagus/enteric acts on muscarinic (M3) receptors -> increased [Ca2+]
2. prostoglandins released from local cells act on EP3 receptors -> increased cAMP
3. histamine released from enterochromaffin like cells act on H2 receptors -> increased cAMP
4. gastrin released from blood stream acts on cholecystokinin B receptors -> increase [Ca2+]

*increased [Ca2+] and cAMP -> translocation of secretory vesicles to parietal cell apical surface -> H+ secretion