6. Pathophysiology of peptic ulcer disease and role of H. Pylori. Causes/risk factors.

Question 1

Define a peptic ulcer and what causes it?

Answer 1

A break in mucosal lining of the stomach/duodenum more than 5mm in diameter with depth to the submucosa (smaller - called erosions)
Caused by excess acid secretion

Question 2

What may a patient experience if a duodenal ulcer has eroded enough to hit blood vessels?

Answer 2

Vomiting blood

Question 3

How is it possible for H Pylori to survive the acidic environment of the stomach?

Answer 3

H. Pylori has high urease enzyme activity.
Urease is involved in the conversion of urea and water into ammonium and bicarbonate.
Therefore, H. Pylori creates a cloud of alkali around itself to neutralise the surrounding acid and protect itself

Question 4

Describe how H. Pylori is involved in the pathophysiology of peptic ulcer disease.

Answer 4

H. Pylori is located near G and D cells which are responsible for detecting pH
These cells are therefore unable to sense the real acidic environment of the stomach because of the alkaline cloud which the bacteria produces.
As a result, more gastric acid is produced.

Question 5

What are the 3 main pathophysiological changes found in peptic ulcer disease?

Answer 5

1. Increase in gastric acid secretion
2. Increase in gastrin release
3. Increase in duodenal acid load

Question 6

What is the increase in gastric acid secretion due to with relation to H. Pylori infection?

Answer 6

Increase in parietal cell mass with no body gastritis

Question 7

What causes the pathological increase in gastrin release with relation to H Pylori?

Answer 7

• decrease in somatostatin release

- more often with Cag +ve strains than Cag -ve strains (cytotoxin-associated gene)

Question 8

What causes the pathological increase in duodenal acid load?

Answer 8

• gastric metaplasia
• H. pylori colonisation
• ulceration

Question 9

What percentage of gastric cancer cases are attributable to H. Pylori?

Answer 9

Over 95%

Question 10

What causes the outcome of duodenal ulcer formation in someone with H. Pylori?

Answer 10

Increase in acid secretion

No atrophy

Question 11

What causes the outcome of gastric cancer in someone with H. Pylori?

Answer 11

Decrease in acid production (G cells are destroyed by inflammation)
Atrophy

Question 12

What determines progression to atrophic gastritis and gastric cancer?

Answer 12

Presence of H. Pylori (from as early as 2-4 years old)
The bacterial strain
Host genetics
Being male
Smoking & diet

Question 13

In those who are H. Pylori negative, are parietal and chief cell densities higher or lower?

Answer 13

Higher

Question 14

Why may H. Pylori positive patients have lower parietal and chief cell densities?

Answer 14

Due to the gastric enteritis producing atrophy of the mucosa

Question 15

What is the % increase in maximal gastric acid secretion in people with peptic ulcers

Answer 15

50%

basal acid levels are also higher

Question 16

What are the factors which aggregate peptic ulcers?

Answer 16

NSAIDs
Gastric juice - HCl, pepsin, refluxed bile salts from duodenum
H. Pylori

Question 17

Why are NSAIDs an aggregating factor of peptic ulcers?

Answer 17

Inhibit COX-1 (indirect) - COX-1 allows PG release to allow inhibition of acid secretion
Traps hydrogen ions (direct)
Can increase bleeding risk via anti platelet action

Question 18

Outline the risk factors associated with peptic ulcer disease

Answer 18

NSAID use
H. Pylori
Smoking
Family history of peptic ulcer disease
Increasing age
Patient in intensive care (mechanical ventilation/coagulopathy)