H.Pylori

Question 1

Describe how acid production is upregulated when stomach pH is increased.

Answer 1

G cells in the Antrum of the stomach increase their secretion of gastrin into the blood
Gastrin binds to ECL cells which produce histamine
Histamine binds to H2 receptors on parietal cells, which in turn increases acid production

Question 2

Describe how acid production is reduced once the target pH has been met.

Answer 2

Once pH has dropped to a suitable level, the d cells in the Antrum produce somatostatin
Somatostatin reduces the amount of gastrin secretion, and so acid secretion also decreases
Negative feedback

Question 3

What surgery can be used to reduce acid in the stomach?

Answer 3

A vagotomy 
- splitting of the vagus nerve to reduce acid production during the Cephalic phase 
A subtotal gastrectomy 
- some of the stomach is removed 
Antrectomy 
- the Antrum is removed

Question 4

What medical treatments are there for lowering acid in the stomach?

Answer 4

H2 receptor agonists

Proton Pump Inhibitors

Question 5

What is the prevalence of H.Pylori like in developing vs developed countries?

Answer 5

Percentages of people in developed countries increased in a cumulative way as they age (10% of 20 yr olds vs 60% of 80 yr olds)
From the age of 10, people in developing countries have the same percentage infected throughout their lives (80% of 10 yr olds vs 80% of 50 yr olds)

Question 6

Is there a relation between social class and H.Pylori infection?

Answer 6

The higher the social class, the lower the risk of being infected.

Question 7

What enzyme does H.Pylori contain and what does it do?

Answer 7

Urease - reacts with urea to produce ammonia and carbon dioxide

Question 8

How are gastric ulcers caused by H.Pylori?

Answer 8

Ammonia produced by H.Pylori kills the d cells in the Antrum, and so less somatostatin is produced.
- Less somatostatin leads to increase gastrin and therefore acid
Also, ammonia tricks the stomach into thinking food is present, and so more acid is produced

Question 9

How is H.Pylori treated medically?

Answer 9

One PPI (for the acid) and two antibiotics (for the bacteria)
First line
- omeprazole
- metronidazole
- amoxicillin (or clarithromycin if allergic to penicillin)

Question 10

What could a patient have if they have simple dyspepsia (trouble swallowing) and a negative H.Pylori test - and how would this be managed?

Answer 10

Oesophagitits - treated symptomatically

Question 11

How many people with dyspepsia and a positive H.Pylori test have ulcer disease?

Answer 11

10-15% - treated with eradication therapy

Question 12

How does gastric cancer normally present?

Answer 12

Anorexia
Weight loss
Anaemia

Question 13

What can cause gastric cancer?

Answer 13

H.Pylori (95%)

Strong genetic predisposition (e.g. Autosomal dominant E-Cadherin germ line mutation)

Question 14

How many people with H.Pylori have no associated disease?

Answer 14

Over 80% - around 50% of the population

Question 15

Risk of gastric cancer with a H.Pylori infection?

Answer 15

Those with H.Pylori who develop a peptic ulcer disease are somehow protected from developing gastric cancer.
Those who don’t have a higher risk of cancer

Question 16

How does gastric cancer develop?

Answer 16

Atrophy of the gastric cells, which leads to chronic atrophic gastritis, which leads to gastric cancer

Question 17

Risk factors for gastric cancer?

Answer 17

Host genetics 
Bacterial strain
Male gender
Smoking
Diet

Question 18

List the ways in which H.Pylori can be tested for.

Answer 18

14C-urea breath test
Biopsy urease test (CLO-test)
Fecal antigen test
Blood test - measuring for blood H.Pylori antibodies
Microscope biopsy

Question 19

Describe how a 14C-urea breath test works.

Answer 19

14c-urea is swallowed into the stomach
H.Pylori contains urease which breaks down the urea into ammonia and carbon dioxide
The carbon dioxide will now be tagged with the 14C
The breath of the patient will then be measured and any 14C carbon dioxide will be detected

Question 20

Describe how a biopsy urease test works.

Answer 20

A small price is the Antrum is extracted and placed in a urea and an indicator (Phenyl red)
If H.Pylori is present, the urease will react with the urea to produce ammonia and carbon dioxide.
The ammonia will increase the pH of the sample, turning the indicator from yellow to red

Question 21

Which type of food causes the treated increase in pH of the stomach?

Answer 21

Protein does the most buffering in the stomach, increases the pH and therefore needs the most acid to be broken down.

Question 22

What are the cells of the stomach and what do they secrete?

Answer 22

Mucous neck cells - mucous
Parietal cells - HCl, bicarbonate and intrinsic factor
ECL cells - histamine
Chief cells - Pepsinogen and gastric lipase
G-cells - gastrin
D-cells - somatostatin

Question 23

Explain the mucous bicarbonate barrier.

Answer 23

The stomach is lined by a single layer of epithelium, which is protected/covered by a layer of mucous
Bicarbonate produced by the parietal cells secrete into the interstitial fluid and then fenestrated capillaries
These travel along the bottom of the pits, and then up the side until they reach the top
Here they dissolve into the mucous layer, and neutralise any acid that they come into contact with

Question 24

Why a re gastric ulcers less common than duodenal?

Answer 24

Because bicarbonate is produced in the same reaction than produces HCl
This means they should always be enough bicarbonate to neutralise the acid in the stomach and protect the epithelium
The duodenum has no such protective mechanism and is more easily damaged

Question 25

What is the effect of H.Pylori on acid production?

Answer 25

HP lives in the mucosal layer, and produces ammonia to protect itself from the acidic surroundings.
This increases the pH of the stomach, and so the g cells provide more gastrin, and the acid levels rise to inappropriate levels

Question 26

Give some examples of H2 receptors agonists.

Answer 26

Cimetidine

Ranitidine

Question 27

What is the mechanism of action of H2 receptor antagonists?

Answer 27

Competitive inhibiton of histamine on the H2 receptors on the parietal cells
This means the parietal cell produces less acid and the pH increases

Question 28

Name some of the most common proton pump inhibitors.

Answer 28

Omeprazole

Lansoprazole

Question 29

Describe the mechanism of action of proton pump inhibitors.

Answer 29

These are administered as enteric coated tablets and are converted to their active form by gastric acid.
They then bind irreversible to a hydrogen/potassium ATPase enzyme (proton pump) on the parietal cells, and blocks hydrogen ion secretion

Question 30

Duration of acid suppression by proton pump inhibitors.

Answer 30

Around 48 hours - however long it takes to replace all of the proton pumps that have a drug bound to it

Question 31

Risk factors for a duodenal ulcer.

Answer 31

Male
Smoker
Stress considered important
Increased acid - both maximal and basal levels