H.Pylori Flashcards
Describe how acid production is upregulated when stomach pH is increased.
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
Describe how acid production is reduced once the target pH has been met.
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
What surgery can be used to reduce acid in the stomach?
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
What medical treatments are there for lowering acid in the stomach?
H2 receptor agonists
Proton Pump Inhibitors
What is the prevalence of H.Pylori like in developing vs developed countries?
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)
Is there a relation between social class and H.Pylori infection?
The higher the social class, the lower the risk of being infected.
What enzyme does H.Pylori contain and what does it do?
Urease - reacts with urea to produce ammonia and carbon dioxide
How are gastric ulcers caused by H.Pylori?
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
How is H.Pylori treated medically?
One PPI (for the acid) and two antibiotics (for the bacteria)
First line
- omeprazole
- metronidazole
- amoxicillin (or clarithromycin if allergic to penicillin)
What could a patient have if they have simple dyspepsia (trouble swallowing) and a negative H.Pylori test - and how would this be managed?
Oesophagitits - treated symptomatically
How many people with dyspepsia and a positive H.Pylori test have ulcer disease?
10-15% - treated with eradication therapy
How does gastric cancer normally present?
Anorexia
Weight loss
Anaemia
What can cause gastric cancer?
H.Pylori (95%)
Strong genetic predisposition (e.g. Autosomal dominant E-Cadherin germ line mutation)
How many people with H.Pylori have no associated disease?
Over 80% - around 50% of the population
Risk of gastric cancer with a H.Pylori infection?
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
How does gastric cancer develop?
Atrophy of the gastric cells, which leads to chronic atrophic gastritis, which leads to gastric cancer
Risk factors for gastric cancer?
Host genetics Bacterial strain Male gender Smoking Diet
List the ways in which H.Pylori can be tested for.
14C-urea breath test Biopsy urease test (CLO-test) Fecal antigen test Blood test - measuring for blood H.Pylori antibodies Microscope biopsy
Describe how a 14C-urea breath test works.
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
Describe how a biopsy urease test works.
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
Which type of food causes the treated increase in pH of the stomach?
Protein does the most buffering in the stomach, increases the pH and therefore needs the most acid to be broken down.
What are the cells of the stomach and what do they secrete?
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
Explain the mucous bicarbonate barrier.
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
Why a re gastric ulcers less common than duodenal?
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
What is the effect of H.Pylori on acid production?
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
Give some examples of H2 receptors agonists.
Cimetidine
Ranitidine
What is the mechanism of action of H2 receptor antagonists?
Competitive inhibiton of histamine on the H2 receptors on the parietal cells
This means the parietal cell produces less acid and the pH increases
Name some of the most common proton pump inhibitors.
Omeprazole
Lansoprazole
Describe the mechanism of action of proton pump inhibitors.
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
Duration of acid suppression by proton pump inhibitors.
Around 48 hours - however long it takes to replace all of the proton pumps that have a drug bound to it
Risk factors for a duodenal ulcer.
Male
Smoker
Stress considered important
Increased acid - both maximal and basal levels
