Peptic ulcer disease

Question 1

Protection

Answer 1

Alkaline mucus
Tight junctions between epithelial cells

Question 2

Peptic ulcers

Answer 2

Higher rate in men than women
15% patients die from ulcer perforation

Question 3

Peritonitis

Answer 3

Bacteria living in stomach and infection rapidly spread into blood
Risk of multiple organ failures

Question 4

Stomach

Answer 4

Alkaline mucus secrete alkaline mucus that Forms thin layer over luminal surface
Mucus content neutralises H+ in epithelium

Question 5

Peptic ulcer disease factors affecting Acid/Pepsin

Answer 5

Helicobacter pylori
Smoking
Genetic factors
Stress

Question 6

Peptic ulcer disease factors affecting mucosal defence

Answer 6

Smoking
Genetic factors
NSAIDs

Question 7

Gastric ulceration

Answer 7

More common in women
Avoid food, hence lose weight

Question 8

Duodenal ulceration

Answer 8

More common in men
No weight loss

Question 9

Protective factors

Answer 9

Bicarbonate layer
Mucus
Blood flow
Cell renewal
Prostaglandins
Phospholipids

Question 10

Damaging factors

Answer 10

Acid
Pepsin
Bile salts
Drugs NSAID
H. pylori

Question 11

Warning signs

Answer 11

Iron-deficient
Anaemic
Chronic blood loss
Weight loss
Progressive dysphagia
Persistant vomiting

Question 12

H. Pylori stats

Answer 12

40% infected
95% gastric ulcer
80% duodenal ulcer

Question 13

H. Pylori

Answer 13

Survives in microaerophil
Infects lower part of stomach
Inflammation of gastric mucosa (asymptomatic)
Colonises antrum of stomach

Question 14

H. Pylori in stomach

Answer 14

Uses Flagella to burrow into mucus lining of stomach where pH is more neutral
Moves towards less acidic environment (chemotaxis)
Adheres to epithelial cells by producing adhesins, bind lipids and carbohydrates
BabA binds to Lewis b antigen displayed
SabA binds to increased levels of sialyl-Lewis x antigen
Produces urease to neutralise acid in stomach

Question 15

Diagnostic testing for H. pylori

Answer 15

Serologic evaluation of antibodies
Urea breath test (UBT)
Stool antigen test (SAT)

Question 16

UBT

Answer 16

Patients swallow a capsule containing urea made from isotope of carbon. Urea broken down and turned into CO2 and excreted through breath

Question 17

Gastric gland in the stomach

Answer 17

Fundus
Body: mucus, pepsinogen, HCL
Antrum: mucus, pepsinogen, gastrin

Contain enterochromafin-like cells: paracrine and histamine
D cells: peptide somatostatin in antral region

Question 18

Cells of the stomach

Answer 18

Parietal oxyntic cells: secrete acid, intrinsic factor
ECL cells: histamine
Chief cells: secrete pepsinogen

Question 19

Canaliculi

Answer 19

Luminal membranes of parietal cells
increase surface area for secretion

Question 20

Parietal cells

Answer 20

Activated by acetylcholine (M3 receptor) or gastrin (CCK-B receptor), increase intracellular calcium concentration, stimulates acid secretion from proton pump on canalicular surface.

Question 21

Enterochromafin-like cells

Answer 21

Stimulate histamine release resulting in activation of adenyl cyclase > increases cAMP and activates protein kinases > proton pump.

Question 22

Gastrin

Answer 22

Secreted by antral G cells
Passes from blood vessels into submucosal tissue of fundic glands, binds to gastrin-CCK-B receptors and ECL cells.

Question 23

Prostaglandin neurones

Answer 23

Vagus nerve stimulates prostaglandin neurones of enteric system to release ACh, binds to M3 receptors

Question 24

Histamine

Answer 24

ECL cells by gastrin (CCK-B receptors)
Acetylcholine (M3 receptors)

Question 25

Acid in stomach

Answer 25

Carbonate exchanged for chlorine Chlorine diffuses into lumen through CIC channel Increased K+ hyperpolarises the membrane potential

Question 26

Treating peptic ulcer disease

Answer 26

Antacids Raising gastric acid pH (>3) Eradication of H. pylori infection Antisecretory agents

Question 27

Histamine receptor antagonists (H2)

Answer 27

Cimetidine Ranitidine Nizatidine Famotidine

Question 28

H2 antagonists actions

Answer 28

Act on parietal cells Reduce acid secretion by 60% Treat duodenal and gastric ulcers Relapse common after treatment

Question 29

H2 antagonists MOA

Answer 29

Histamine released from ECL by gastrin/vagal stimulation is blocked

Question 30

H2 antagonists side effects

Answer 30

Diarrhoea Headache Confusion in elderly

Question 31

Cimetidine

Answer 31

Gynaecomastia (anti-androgen effect) Inhibits CYP450 Potential interactions with Warfarin, Phenytoin, Theophylline

Question 32

Proton Pump Inhibitors

Answer 32

Omeprazole Lansoprazole Pantoprazole Rabeprazole Esomeprazole

Question 33

PPIs chemistry

Answer 33

Irreversible inhibitors of proton pump Bind covalently via disulphide bond 90% acid production inhibition

Question 34

PPIs side effects

Answer 34

GI upset Headache Skin rashes Long term - gastric atrophy

Question 35

Omeprazole

Answer 35

Stimulates and inhibits CYP450 Reduces elimination of diazepam, phenytoin and warfarin - inhibition of hepatic metabolism

Question 36

H. pylori medications

Answer 36

PPI Amoxicillin Clarithromycin/metronidazole (twice daily for a week) Combination antibiotic therapy for severe cases

Question 37

Misoprostol

Answer 37

Enhanced duodenal bicarbonate secretion Increased mucosal blood flow Not used in pregnancy (induces abortion)

Question 38

Zollinger-Ellison Syndrome

Answer 38

Rare disorder causing ulcers Caused by non-beta islet cell

Question 39

GORD

Answer 39

Normal acid secretion Incompetent lower oesophageal sphincter

Question 40

Treating GORD

Answer 40

Antacid and alginates H2 antagonist PPI Laparoscopic surgery if severe

Question 41

Barrett's oesophagus

Answer 41

Long term GORD Replacement of stratified squamous epithelium by columnar epithelium with goblet cells