PUD

Question 1

4 major regions of the stomach

Answer 1

Cardia: Next to sphincter, guards the stomach
Fundus: Expansion area for food + swallowed air
Corpus: produces secretions
Pyloric Antrum: “Grinds” food with gastric secretions then producing “Chyme”

Question 2

Stomach anatomy

Answer 2

Exocrine: HCL, electrolytes (Na+, K+), Pepsinogen, intrinsic factors
Endocrine: Gastrin, ghrelin
Paracrine: Histamine, somatostatin

Question 3

Stomach histology

Answer 3

Gastric pit + mucous neck cells: Epithelial cells containing mucus cells to provide stomach lining (100um thick barrier - traps bicarbonate)
Chief cells: Has pepsinogen which can convert to pepsin for breakdown of proteins
Parietal cells: Produces HCl + intrinsic factor

Question 4

Chief cells

Answer 4

Has pepsinogen containing secretory granules (zymogen granules) which break down proteins
Contains the Acetylcholine receptor

Question 5

Parietal cells - major receptors + regulation of acid secretion

Answer 5

3 major receptors
Histamine H2 receptor (reason for antihistamine use)
Muscarinic M3 receptor (AcH pathway)
Gastrin receptor
Regulation of acid secretion done by
- Histamine, AcH, Gastrin, PGE2 + PGI2, Somatostatin
Acid secretion done by proton pump and acid produced by
co2 + H2O —> H2CO3 —> HCO3- + H+ (Acid) which is transported out via proton pump

Question 6

Mucus layer

Answer 6

95% water + 5% mucins (insoluble gel)
100um barrier traps bicarbonate and neutralises environment
Bicarbonate ions produce neutral pH (7.0) when the luminal pH around is 2.0
Contains PGE2 which stimulates mucus + phospholipid secretion

Question 7

Gastrin (G) and acid regulation

Answer 7

Gastrin is made in the G cells —> Gastrin activates ECL cell —> ECL cells —> Histamine release —> histamine binds to H2R on parietal cells —> acid secretion occurs from parietal cells
ECL cells also activated by somatostatin and PGE2

Question 8

Alarm signs / red flags

Answer 8

Sudden weight loss
Vomiting
Swallowing pain
Mass presence
Anaemia
Bleeding
Dysphagia (swallowing difficulty)

Question 9

Peptic ulcers

Answer 9

Ulcer of the alimentary tract mucosa in the stomach or duodenum
Rarely in lower oesophagus
Mucosa exposed to G acid secretion
It’s deep enough to penetrate mucosa
Patients present with dyspepsia

Question 10

Duodenal ulcers (DU) pathophysiology

Answer 10

Occurs from increased acid due to:
- Increased parietal cell mass
- Increased gastric secretion (e.g. via alcohol or Zollinger-Ellison syndrome)
Less inhibition of acid secretion (by H pylori)
Smoking affecting gastric mucosal healing
Genetics may play part
H pylori inflammation causing HCO3- secretion to decrease in duodenum (pH gets acidic)
Acid hyper-secretion mainly caused by H pylori, goes back to normal after eradication

Question 11

Gastric ulcer (GU) pathophysiology

Answer 11

GU results from breakdown of Gastric mucosa
Associated with gastritis affecting body + antrum
Epithelial damage happens due to of cytokines released from H pylori + abnormal mucus production
Parietal cell damage

Question 12

PUD complications

Answer 12

Upper GI bleeding: life threatening, bloody vomit/stools
Ulcer perforation: penetrate through stomach wall. Causes content spillage
Pyloric stenosis: mechanical obstruction from scarring / oedema
Penetration: ulcer penetrates stomach muscle walls then continues to organs (liver/pancreas)

Question 13

PUD RFs

Answer 13

Age - 65 +
High NSAD use or more than one NSAID
Previous PUD
Anticoagulant risk - bleeding risk
Corticosteroid use

Question 14

PUD causes

Answer 14

NSAIDs
H pylori
Smoking
Alcohol
Stress
Reduced bicarbonate secretion

Question 15

NSAID + PUD

Answer 15

Arachidonic acid —> COX 1 + COX 2 Production —> PGE2 production

PGE2 needed for mucus production to protect the stomach

NSAIDs block COX 1 + COX 2 enzymes —> Decrease PGE2 —> decreased mucosal layer —> increased PUD risk

Question 16

What is H pylori

Answer 16

Gram negative bacteria
Has virulence factors allowing it to adhere to + inflame gastric mucosa

Question 17

Treatment - lifestyle changes

Answer 17

Stop smoking
Reduce NSAID use
Diet / weight loss
Reduce alcohol
Reduce stress

Question 18

NICE guidelines for PUD

Answer 18

First test for H pylori and eradicate if positive
1st line = PPI or H2RA
2nd line = endoscopy + retesting for H pylori
Stop NSAID use

Question 19

OTC antacids

Answer 19

Contain sodium +/or Calcium carbonate to neutralise excess acid
Effectively neutralise stomach acid

Question 20

PPIs MOA + clinical use

Answer 20

Benzimidazole derivatives
1st line drugs
Inhibits G proton pump —> decreased G acid secretion from parietal cell
Inactive pro-drugs carried in bloodstream to parietal cells
Cross parietal cell membrane to cytosol
Converted to active form when in an acidic environment
Irreversibly binds to proton pumps sulphydryl (-SH) groups
Inhibits Acid secretion
Use:
- relieves symptoms + heal ulcers quicker than H2RA

Question 21

Histamine receptor antagonists (H2RA) MOA + use

Answer 21

Block H2R in gastric parietal cells
Inhibit Histamine + Gastrin acid secretion: pepsin also falls with reduction in volume of gastric juice
Prevent gastric acid secretion
All drugs have similar properties (all effective at same time of day)
Less effective than PPIs - but H2Rs reduce acid secretion in response to neuronal or hormonal secretion
USE:
Heal ulcers in patients who discontinue NSAIDs
E.g. ranitidine, cimetidine, famotidine
Main role = management of dyspepsia symptoms

Question 22

Anticholinergics

Answer 22

Pirenzepine mainly used - inhibits gastric acid secretion at low doses
MOA:
- Muscarinic M1-antagonist
- Blocks ACh mediated H release from paracrine cells inhibiting G acid secretion
Use:
- PUD + original anti ulcer drugs

Question 23

Cytoprotective: misoprostol

Answer 23

Gastro protective: given when patients prescribed NSAIDs (maybe long term) for other conditions
Similar structure to PGE2
Increases mucus levels which NSAIDS decrease and bicarbonate levels
Decreases acid secretion

Question 24

H pylori eradication

Answer 24

Confirm infection first
Clarithomycin or amoxicillin
If allergic to penicillin - metronidazole 400mg or Levofloxacin 250mg
Clarithomycin - inhibits protein production
Amoxicillin disrupts peptidoglycan wall
Both lead to H pylori death
1st line therapy for 7 days:
- PPI twice daily + amoxicillin 1g twice daily +
either Clarithomycin 500mg twice daily OR metronidazole 400mg twice daily
If allergic to penicillin:
- PPI twice daily + Clarithomycin 500mg twice daily + metronidazole 400mg twice daily