L13- Helicobacter Pylori Flashcards
Genus helicobacter
34 species
Bacteriology:
- Gram negative
- spiral-shaped bacterium
- with 4–6 unipolar flagellae
- Microaerophilic (5% O2) growth condition.
- Strongly urease positive
- Survives in acid pH only in the presence of urea.
Various other non-pylori Helicobacter species also found in human and other vertebrates.
Originally mistook as campylobacter
Bacteriology of HP
- Gram negative
- spiral-shaped bacterium
- with 4–6 unipolar flagellae
- Microaerophilic (5% O2) growth condition.
- Strongly urease positive (key for many diagnostic tests)
- Survives in acid pH only in the presence of urea.
Epidemiology of HP
- World-wide distribution
- Global prevalence >50%
- Prevalence in developing countries generally higher than developed countries (High prevalence in Asia)
- Infection mainly acquired during childhood; prevalence increases with age
- Human is the only significant natural reservoir
Mode of transmission of HP
1) Person-to-person (most likely)
- gastro-oral (vomitus)
- faeco-oral
- oral-oral
2) Nosocomial transmission - contaminated endoscopes may cause HP infection
3) Drinking water and food (e.g. milk) - contamintaed ingested materials are possible vehicles in rural areas or developing countries
HP Infection risk factors
1) Poor socio-economical development
2) Low education
3) Poor hygiene (esp. in childhood)
4) Crowded family
5) No sanitary drinking water
6) No sanitary sewage disposal system
Foci of infection of HP
1 Natural niche: gastric antral epithelium; other parts of stomach: fundus, body.
2 Unnatural niche: foci of peptic ulceration, e.g. gastric metaplasia in duodenum.
3 Bacteria mainly found in mucus gel layer over gastric epithelium, a smaller number of bacteria attach to the surface of the epithelial cells. Invasion of the bacteria intracellularly into the epithelial cells and into the lamina propria has also been observed.
Virulence factors of HP
1. Colonization: urease, motility by falgella, adherence
2. Persistence: inaccessibility to immune attack (in mucus gel layer?)
3. Altered gastric physiology as a result of infection and inflammation.
4. Various virulence factors such as vacuolating cytotoxin (vacA gene), cytotoxin- associated gene A protein (cagA gene) playing a part in tissue injury and carcinogenesis.
5. Other enzymes like phospholipase, catalase, mucinase
Direct pathology of HP
1) Clinical Disease only in 10-15% of infected individuals
2) A chronic infection. Inflammation always present.
3) Chronic superficial gastritis: mononuclear inflammatory cell and neutrophil infiltration. Variable degree of inflammation: from minimal changes to severe dense inflammation and micro-abscess formation.
4) Atrophy of glandular gastric epithelium
Disease related to HP
Clinical Diseases only in 10-15% of infected:
1) Chronic superficial gastritis: often asymptomatic
- Antrum predominant gastritis (non-atrophic)
- Non-atrophic gastritis
- Corpus predominant gastritis (atrophic)
- Pan-gastritis (atrophic)
2) Peptic ulcer disease
- Duodenal ulcer
- Gastric ulcer
3) Gastric adenocarcinoma of body and antrum
- Usually arises from chronic atrophic gastritis
4) Gastric MALT lymphoma
5) Non-ulcer dyspepsia
6) Extra-gastric diseases such as:
- unexplained iron-deficiency anaemia
- idiopathic thrombocytopenic purpura
- cardiovascular, respiratory, haematological, endocrine, hepatobiliary, neurological, eye, and skin disorders
Disease Outcome:
Symptomatic infections usually develop into wither duodenal ulcer disease or gastric adenocarcinoma. NEVER BOTH.

Chronic Antral-predominant gastritis
- A symptomatic chronic superficial gastritis caused by HP infection
- non-atrophic
- Gastric acid hypersecretory - the gastritis will stimulate increased secretion of gastrin by antral G cells and decreased secretion of somatostatin by antral D cells; this will affect the ECL cells in fundus to increase histamine production; as a result, parietal cells will release more HCl
- may lead to the formation of duodenal ulceration or resolve into asymptomatic chronic superficial gastritis
Chronic non-atrophic gastritis
- An asymptomatic chronic superficial gastritis caused by HP infection
- non-atrophic
- Gastric acid secretion not affected
- may lead to the formation of Gastric MALT lymphoma or resolve into asymptomatic chronic superficial gastritis
Pan-gastritis
- A symptomatic chronic superficial gastritis caused by HP infection
- Atrophic
- Gastric acid hyposecretory
- At the antrum, the gastritis will stimulate increased secretion of gastrin by antral G cells and decreased secretion of somatostatin by antral D cells
- However at the fundus and corpus, the inflammation will lead to atrophy of parietal cells, as a result less acid can be produced
- may lead to the formation of Gastric ulcer, Gastric adenocarcinoma (through metaplasia and dysplasia) or resolve to asyptomatic superficial gastritis
Corpus-predominant gastritis
- A symptomatic chronic superficial gastritis caused by HP infection
- atrophic
- Gastric acid hyposecretory - at the fundus and corpus, the inflammation will lead to atrophy of parietal cells, as a result less acid can be produced
- may lead to the formation of Gastric ulcer, Gastric adenocarcinoma (through metaplasia and dysplasia) or resolve to asyptomatic superficial gastritis
Duodenal ulcer
- 95% caused by HP (100% excluding NSAID-induced)
- More common of peptic ulcer disease
- Predominant in the lesser curvature of antrum and cardia
- Gastric acid hypersecretion: at antrum, ulcer will stimulate increased secretion of gastrin by antral G cells and decreased secretion of somatostatin by antral D cells; this will affect the ECL cells in fundus to increase histamine production; as a result, parietal cells will release more HCl
Gastric ulcer
- 70% caused by HP (80-90% excluding NSAID-induced)
Gastric adenocarcinoma
- Location: Pan-gastric, i.e. Greater & Lesser curvature of cardia, body, antrum & pylorus
- Relative risk = 4-9
- Usually result from atrophic gastritis
- Gastric acid hyposecretory
- At the antrum, the gastritis will stimulate increased secretion of gastrin by antral G cells and decreased secretion of somatostatin by antral D cells
- However at the fundus and corpus, the inflammation will lead to atrophy of parietal cells, as a result less acid can be produced
Gastric MALT lymphoma
mucosa-associated lymphoid tissue (MALT)-type low grade B cell lymphoma.
HP-induced extra-gastric diseases
- unexplained iron-deficiency anaemia
- idiopathic thrombocytopenic purpura
- cardiovascular, respiratory, haematological, endocrine, hepatobiliary, neurological, eye, and skin disorders
(etiology unknown)
Diagnostic methods of HP
1) Clinical symptomology
2) Bacteriological diagnosis
3) Histopathological diagnosis
4) Antibody detection (serology)
5) Stool antigen detection tests
6) Urease-based tests
7) PCR
Bacteriological diagnosis (culture) of HP
Specimen:
- endoscopic gastric mucosal biopsies
- transported in sterile saline
- Microaerophilic culture.
Potency:
- 50–95% sensitivity compared to histopathology
- Problem of sampling error (only a limited surface sample is taken for biopsy; may miss HP colony)
Notes:
Essential for antibiotic sensitivity testing, especially in patients who had treatment failures due to antibiotic resistance.
Histopathological diagnosis of HP
1) Endoscopy-based.
2) At least 2 biopsies required.
3) Recognized by its characteristic morphology, position, diffuse distribution, and presence of inflammation.
4) Stains: haematoxylin and eosin, Warthin-Starry (a silver stain); immunostaining.
HP Antibody detection (serology)
1) Chronic infection: ↑ IgG, IgA. Commonest method used is ELISA.
2) Sensitivity and specificity depends on nature of antigen used. Average sensitivity 85%, specificity 79%.
3) After eradication of H. pylori, antibody level tends to decrease (to half of pre- treatment level by 6 months) but variable rate of decline.
4) Urine and saliva antibody tests also available.
5) Not commonly used for diagnosis clinically due to inability to distinguish between active & past infections. More useful for epidemiological studies.
Stool antigen detection tests for HP
Stool antigen detection by:
1) enzyme immunoassay (EIA)
- office-based
- relatively lower sensitivity
- very rapid
2) immunochromatographic assays (ICA)
- laboratory-based
- better accuracy and higher sensitivity
- newer generations uses monoclonal antobodies
Rapid Urease Test
- Using biopsy specimens of gastric mucosa (aka biopsy urease test)
- Medium: Urea & pH indicator
- HP in gastric mucosa, once in contact with urea in medium, will catalyse the conversion of urea to ammonia, water & CO2 via urease. Ammonia will increase the pH, causing the pH indicator in medium to change colour
- (Red - urease positive; Yellow - negative)
- Results available in 1-24 hours
- Very good overall sensitivity