Peptic Ulcers

Question 1

Define 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 the 2 different ulcers be distinguished?

Answer 2

Based on TIMING of symptoms:

Gastric ulcer
• pain at mealtimes when acid is secreted

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

Question 3

Explain the protective factors of the GI barrier

Answer 3

Lubricate the food and protect the mucosal surface:

• mucus from gastric mucosa creates a gastrointestinal mucosal barrier
• HCO3- ions are trapped in the mucous and generate a protective pH of 6-7 at the mucosal surface
• locally produced prostaglandins stimulate mucus and bicarbonate production (paracrine action), inhibit gastric acid secretion and facilitate a good blood supply to the stomach.

Question 4

Some factors that convert the food into chyme can damage the mucosal barrier - explain

Answer 4

Parietal cells
– acid secretion from parietal cells of the oxyntic glands in the gastric mucosa

Chief cells
– pepsinogens which erode the mucous layer

Question 5

Factors that contribute to mucosal damage?

Answer 5

o Increased acid or decreased HCO3-

o Decreased thickness of mucosal layer

o Increase in pepsin type 1

o Decreased mucosal blood flow

o Infections with H. pylori

o Risk factors – genetics, stress, diet (alcohol, smoking)

Question 6

5 types of drugs for anti-ulcers?

Answer 6

1. Antibiotics
   • eradicate H.pylori
2. Inhibitors of gastric acid secretion
   • prevent gastric acid production
3. Cytoprotectice drugs
   • promote healing
4. Antacids
   • neutralise gastric acid
5. Triple therapy

Question 7

Why are antibiotics used as a drug against peptic ulcers?

Answer 7

Eliminates H.pylori

• cause of ~100% dudodenal & ~80-90% gastric ulcers

Question 8

How does H.pylori contribute to ulcer formation?

Answer 8

1. Increased gastric acid formation
   • increase gastrin OR decrease somatostain
2. Gastric metaplasia
   • due to excessive acid exposure
3. Downregulation of defence factors
   • decrease epidermal GF
   • decrease HCO3- production

Question 9

What contributes to the virulence of H.pylori?

Answer 9

Urease

1. Catalyses urea –> ammonium chloride + monochloramine
   • damages epithelial cells
2. Antigenic
   • evokes I.R
3. Certain strains produce CagA (antigenic) & VacA (cytotoxic)
   • more intense tissue inflammation

Question 10

Example antibiotics used?

Answer 10

Amoxicillin

Clarithromycin/Metronidazole

(antibiotics used agaisnt H.pylori)

Question 11

What is included in gastric acid inhibitors?

Answer 11

1. Proton pump inhibitors
2. H2 receptor antagonists
3. Anti-muscarinics

Question 12

Drugs associated with the inhibitors of gastric acid secretion

Answer 12

1. Proton pump inhibitors
   • Omeprazole
2. H2 receptor antagonists
   • Cimetidine, Ranitidine

Question 13

Explain how gastric acid is produced in the body

Answer 13

1. Presence/smell of food can trigger acid production
2. In the fundus, there are acid-secreting parietal cells
   • PNS can act on H-cells to stimulate histamine production
3. In the antrum, aa can trigger the g-cells to secrete gastrin
   • gastrin triggers MORE histamine release OR can simply trigger MORE acid production directly (CCKB receptors)

 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
 Superficial epithelial cells provide the protective HCO3- secretion which mixes with the mucus to protect.

Question 14

MoA of PPIs e.g. Omeprazole

Answer 14

Inhibits basal and stimulated gastric acid secretion by >90%

MoA
• irreversible inhibitor of the H+/K+ ATPase exchanger

Becomes inactive at neutral pH – limits the action on other PPs around the body

Accumulates at the canaliculi as it is a weak base – concentrates action at the canaliculi

Question 15

How do PP work and contribute to ulcer formation?

Answer 15

Expressed on secretory vesicles within parietal cells
• increase [Ca2+] = increase cAMP = secretory vesicles translocate to parietal cell apical surface = H+ secretion

Ulcer formation:
• increased activity of PP = increased H+ secretion = reduction in gastric pH

Question 16

MoA of H2-receptor antagonists?

Answer 16

Inhibit gastric acid secretion by parietal cells
• LESS effective than PPIs
• MoA = competitive H2-receptor antagonists

Question 17

What is an issue with H2-receptor antagonists however?

Answer 17

Relapse are LIKELY after withdrawal from treatment

• HENCE is part of triple therapy

Question 18

What helps regulate gastric acid?

Answer 18

1. ACh
   • released from neurones
   • acts on muscrainic receptors (M3)
   • INCREASE [Ca2+] = increase H+
2. Prostaglandins
   • released from local cells
   • act on EP3 receptors
   • DECREASED cAMP = increase H+
3. Histamine
   • released from enterchromaffin-like cells
   • acts oh H2-receptors
   • INCREASE cAMP = increase H+
4. Gastrin
   • released from G-cell
   • acts on cholecystokinin B receptors
   • INCREASE [Ca2+] = increase H+

Question 19

Explain what molecules have an effect on gastric acid secretion

Answer 19

o INCREASED [Ca2+] & cAMP
• translocation of secretory vesicles to PARIETAL CELL apical surface
• INCREASE H+ SECRETION

o Somatostatin
• peptide that inhibits G-cells, ECL cells & parietal cells