Peptic ulcers (Block 5)

Question 1

Neuronal control of GI tract

Answer 1

Blood vessels, smooth muscle and glands
Myenteric plexus and submucosal plexus
Acetylcholine and noradrenaline
Also GABA, serotonin, purines and nitric oxide
Peptides: VIP, cholecystokinin, etc.

Question 2

Hormonal control of the GI tract - endocrine hormones

Answer 2

Release into bloodstream
Gastrin (G-cells): stimulates acid secretion in stomach
Cholecystokinin (duodenum): stimulates vagal afferents after fatty meal

Question 3

Hormonal control of GI tract - paracrine hormones

Answer 3

Released locally
Histamine (ECL cells): stimulates acid release from nearby parietal cells
Secretin (duodenum): stimulates bicarbonate release from pancreas
Somatostatin (D-cells): inhibits gastrin and histamine release

Question 4

Gastric pits

Answer 4

Massively increase surface area -> increases secretion of key hormones and anything that aids digestion
Made of parietal cells, chief cells, enteroendocrine cells

Question 5

6 key types of stomach cells

Answer 5

Parietal cells
ECL cells
D-cells
G-cells
Foveolar cells
Chief cells

Question 6

Parietal cells

Answer 6

Produce acid (HCL) for digestion of food

Question 7

Chief cells

Answer 7

Release enzymes needed for digestion of proteins.

Question 8

Foveolar cells

Answer 8

Produce special type of mucus consisting of water, mucin and surfactants

Question 9

G-cells

Answer 9

Produce hormone gastrin which enhances acid production by parietal cells

Question 10

D-cells

Answer 10

Produce somatostatin which inhibits acid production by parietal cells

Question 11

ECL cells

Answer 11

ECL cells or enterochromaffin-like cells: Produce histamine which enhances acid secretion from parietal cells

Question 12

Secretagogues

Answer 12

Regulation of acid secretion
Gastrin
Histamine
Acetylcholine
Somatostatin
Prostaglandins

Question 13

Mechanism of acid secretion

Answer 13

Antiport (A): HCO3- vs Cl-
Symport carrier (C): K+ vs Cl-
Proton pump (P): H+ vs K+

Question 14

Peptic ulcers

Answer 14

Damage to the GI tract
In appropriate build up of acid

Question 15

Causes of peptic ulcers

Answer 15

Stress
Diet
Alcohol
Obesity
H. Pylori
NSAIDs

Question 16

H. Pylori

Answer 16

Gram negative bacteria
Almost all gastric ulcer biopsies were infected with h.pylori
Now implicated in gastric ulcers, duodenal ulcers, and gastric cancer
Carriers have 1020% lifetime risk of gastric ulcer and 1-2%% risk of stomach cancer

Question 17

Treatment options for ulcers

Answer 17

Antacids
Secretion inhibitors (H2 antagonists, proton pump inhibitors)
Mucosal protectants
Eradication of H.pylori

Question 18

Antacids

Answer 18

Dyspepsia and symptomatic relief from peptic ulcers
Increase gastric pH to ~5 by direct acid neutralization
Inhibit conversion of pepsinogen to pepsin
Aluminium and magnesium salts:
Al hydroxide: slow to dissolve, long duration, constipation
Mg hydroxide: rapid onset, laxative
Mg trisilicate: prolonged effect, adsorbs pepsin
Alginates: increase viscosity and adherence of mucus

Question 19

H2 antagonists

Answer 19

Comp inhibition of histamine effects at H2 receptors
Main effect is reduction of histamine and gastrin -> stimulated gastrin secretion; also promote healing of peptic ulcers
Low-dose forms are available over-the-counter

Question 20

Proton pump inhibitors

Answer 20

Amongst most widely prescribed drugs worldwide
Potent, selective, irreversible inhibition of HH+ K+ ATPase (or proton pump)
Terminal and commo step in acid secretion of parietal cell
Prodrugs and weak bases

Question 21

Proton pump inhibitors - main compounds

Answer 21

Omeprazole (Losec®), lansoprazole (Loton®)
Omeprazole is enteric coated to protect it from degradation by acid!
Half-life ~1h but effects last ~3 days; synthesis of new H+ K+ ATPase
Adverse effects relatively uncommon; headache, diarrhoea, rash

Question 22

Treatment of H.pylori infection

Answer 22

Symptoms of peptic ulceration?
Test for H. pylori – blood antibody, stool or breath test, endoscopic biopsy
If positive, treat with antibiotics and proton pump inhibitors:
Standard one-week triple therapy: clarithromycin, amoxicillin, omeprazole
Penicillin allergy: replace amoxicillin with metronidazole
Levofloxacin for clarithromycin-resistant strains
Bismuth chelate added – quadruple therapy – prevents bacillus adherence to mucosa
Triple therapy eradicates H. pylori and is curative but re-infection can occur
Yogurt drinks proposed to prevent or limit effects of infection

Question 23

Misoprostol

Answer 23

Stable synthetic analogue of PGE1
Co-prescribed with NSAIDs during long-term use
Direct action via EP2 receptor on ECL cells -> inhibits basal secretion of gastric acid and increased production in response to food; enhances muscus and bicarbonate production, helping to balance acid
Can initiate uterine contraction so contraindicated in pregnancy