Treatment of peptic ulcers

Question 1

Common presentation of peptic ulcer

Answer 1

Epigastric pain, burning sensation after meals

Question 2

Investigations of peptic ulcer

Answer 2

Carbon-urea breath test

Stool antigen test (H pylori)

Question 3

Pathophysiology of H pylori positive peptic ulcer

Answer 3

H pylorus:

• dissolves mucus layer (epithelial cells more susceptible to damage from the acidic environment of stomach)
• epithelial cell death

ULCER

Question 4

Treatment of h pylori positive peptic ulcer

Answer 4

Antibiotics for H Pylori (amoxicillin &
clarithromycin/metronidazole)

Proton Pump Inhibitor reduces acid production

Question 5

What type of bacterial is helicobacter

Answer 5

Gram negative, motile, microaerophilic bacterium

Question 6

Where does H pylori reside

Answer 6

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

Question 7

How does H pylori affect the GI tract to lead to ulcer formation

Answer 7

1. Increased gastric acid formation
2. Gastric metaplasia
3. Downregulation of defence factors

Question 8

How does H pylori increase acid formation

Answer 8

Increase gastrin or reduce somatostatin

Question 9

How does H pylori downregulate defence factors

Answer 9

Reduces epidermal growth factor and decreases bicarbonate production

Question 10

How does H pylori cause gastric metabplasm a

Answer 10

(cell transformation due to excessive acid exposure)

Question 11

What is the virulence of H pyori

Answer 11

Urease

and

Certain strains produce CagA or VacA

Question 12

How does urease from H pylori cause virulence

Answer 12

1. catalyses urea into ammonium chloride &monochloramine –>

damage epithelial cells

2. Urease is antigenic and evokes immune response

Question 13

How do CagA and VacA cause virulence in H Pylori

Answer 13

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

Question 14

What differentiates acute and chronic peptic ulcer

Answer 14

Acute- just pain and burning after food

Compicated- constant pain and burning

Question 15

Treatment for complicated peptic ulcer

Answer 15

Antibiotics for H Pylori (amoxicillin & clarithromycin/metronidazole)

Consider quinolone, tetracycline

Proton Pump Inhibitor (omeprazole) – 4-12 weeks

Question 16

How to proton pumps work

Answer 16

Acid from parietal cells

H+-K+-ATPase

Expressed on secretory vesicles within parietal cells (NOT USUALLY EXPRESSED ON THE CELL MEMBRANE, UNTIL ACTIVATION)

Question 17

What leads to acid secretion

Answer 17

Increased [Ca2+], inreased cAMP, translocation of secretory vesicles to parietal cell apical surface, leads to H+ secretion

Question 18

What can occur in ulcer formation with proton pump

Answer 18

Increased activity of proton pump – increased H+ secretion leads to reduction gastric pH

Question 19

After H pylori, what is the next most common cause of peptic ulcer

Answer 19

NSAID

Question 20

How can NSAID induce peptic ulder

Answer 20

Directly cytotoxic

Reduces mucus production

Increases likelihood of bleeding

Increased acidity leads to peptic ulcer

Question 21

Treamtent for NSAID related peptic ulcer

Answer 21

Removal of NSAID

Proton Pump Inhibitor or histamine H2 receptor antagonist (Ranitidine) – 4-8 weeks

H2 receptor increases acid secretion

NO ABs!!!!

Question 22

4 main types of receptors on the parietal cells, the agonists, and where these agonists come from

Answer 22

1. M3-R (ACh, neurons)
2. EP3-R (PGs, local cells)
3. H2-R (Histamine, ECL cell)
4. CCKB-R (Gastrin, bloodstream)

Question 23

Outline the action of the ACh receptor for gastric acid regulation

Answer 23

Released from vaus of enteric nerves–> Increased [Ca2+]

Question 24

Outline the action of the prostaglandngs receptor for gastric acid regulation

Answer 24

Increasing cAMP

Question 25

Outline the action of histamine receptor on gastric acid regulation

Answer 25

Increasing cAMP

Question 26

How does action of gastrin affect fastric acid regulation

Answer 26

Gastrin released from blood stream acts on cholecystokinin B receptors - increass [Ca2+]i

Question 27

What can result in the increased gastric acid secretion

Answer 27

inreased [Ca2+]i & increased cAMP leads to translocation of secretory vesicles to parietal cell apical surface leads to H+ secretion

Question 28

How does H pylori lead to

i. Dissolve of mucus layer
ii. Epithelial cell death

Answer 28

i. Urease enzyme

ii. exotoxins (cagA, vacA) and inflammation