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Gastrointestinal Block > L13- Helicobacter Pylori > Flashcards

L13- Helicobacter Pylori Flashcards

1
Q

Genus helicobacter

A

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

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2
Q

Bacteriology of HP

A
  • 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.
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3
Q

Epidemiology of HP

A
  • 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
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4
Q

Mode of transmission of HP

A

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

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5
Q

HP Infection risk factors

A

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

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6
Q

Foci of infection of HP

A

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.

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7
Q

Virulence factors of HP

A

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

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8
Q

Direct pathology of HP

A

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

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9
Q

Disease related to HP

A

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.

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10
Q

Chronic Antral-predominant gastritis

A
  • 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
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11
Q

Chronic non-atrophic gastritis

A
  • 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
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12
Q

Pan-gastritis

A
  • 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
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13
Q

Corpus-predominant gastritis

A
  • 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
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14
Q

Duodenal ulcer

A
  • 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
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15
Q

Gastric ulcer

A
  • 70% caused by HP (80-90% excluding NSAID-induced)
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16
Q

Gastric adenocarcinoma

A
  • 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
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17
Q

Gastric MALT lymphoma

A

mucosa-associated lymphoid tissue (MALT)-type low grade B cell lymphoma.

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18
Q

HP-induced extra-gastric diseases

A
  • unexplained iron-deficiency anaemia
  • idiopathic thrombocytopenic purpura
  • cardiovascular, respiratory, haematological, endocrine, hepatobiliary, neurological, eye, and skin disorders

(etiology unknown)

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19
Q

Diagnostic methods of HP

A

1) Clinical symptomology
2) Bacteriological diagnosis
3) Histopathological diagnosis
4) Antibody detection (serology)
5) Stool antigen detection tests
6) Urease-based tests
7) PCR

20
Q

Bacteriological diagnosis (culture) of HP

A

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.

21
Q

Histopathological diagnosis of HP

A

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.

22
Q

HP Antibody detection (serology)

A

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.

23
Q

Stool antigen detection tests for HP

A

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
24
Q

Rapid Urease Test

A
  • 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
25
Q

Urea breath Test

A
  • Using Urea solution with labelled carbon isotopes (i.e. radioactive 14C or non-radioactive 13C)
  • Subject will ingest the urea solution. HP in gastric mucosa will convert the ingested urea to ammonia, water and CO2. Thus the expired CO2 will contain labelled carbon if HP is present.
  • 14C test not recommended for children and pregnant women due to radioactivity
  • Most of the current urea breath tests use 13C.
26
Q

Endoscopic biopsy in diagnostic tests for HP

A

Biopsy required:

  • Rapid Urea Test
  • Bacteriology (culture)
  • Histopathological diagnosis
  • PCR

Biopsy not required:

  • Urea breath test
  • Serology
  • Stool antogen detection test
  • PCR
27
Q

Aim of HP management

A
  • To cure peptic ulcer disease and reduce the lifetime risk of gastric cancer.
28
Q

Clearance vs. eradication

A

Clearance = absence of detectable organisms immediately after stopping therapy.

Eradication = absence of detectable organisms ≥4 weeks after stopping therapy.

29
Q

Difference between in vitro and in vivo antibiotic sensitivity

A

In vitro antibiotic sensitivity ≠ clinical efficacy, because:

  • pH stability of antibiotic in acidic gastric environment
  • Penetration ability of antibiotic into the mucus gel coat where HP is located
30
Q

Follow up after eradication

A

1) Urea breath test: the preferred method for assessing the success of therapy.

2) A laboratory-based, validated, stool antigen detection assay - Immunochromatigraphic Assay (ICA)

3) Serology not useful - as titre only decreases after 6-12 months

31
Q

Recurrence after eradication

A
  • Generally less common in developed countries.
  • Ranges from 2.67% to 13%.
32
Q

Agents used for eradication of HP

A

Mneumonic: Tummy And Cardia Better Right _N_ow _P_lease

1) Tetracycline

2) Amoxillin

3) Clarithromycin

4) Bismuth compounds

  • Pepto-Bismol (bismuth subsalicylate)
  • DeNol (tripotassium dicitrato bismuthate)
  • Pylera (bismuth-metronidazole-tetracycline)

5) Ranitidine bismuth citrate

6) Nitroimidazoles

  • metronidazole
  • tinidazole

7) PPI (proton-pump inhibitors)

  • Omeprazole
  • Esomeprazole
  • Lansoprazole
    (- Pantoprazole
  • Rabeprazole)
33
Q

Tetracycline

A
  • Stable in acidic pH
  • High topical concentration
  • Contraindicated in children (<8 years) and pregnant women
  • Occurrence of resistance rare.
34
Q

Amoxillin

A
  • ß-lactam antibiotic
  • Acid-stable
  • more active at neutral pH
  • Occurrence of resistance rare.

Side effects:

  • Hypersensitivity reactions (rash, fever, anaphylactic shock)
  • Gastrointestinal disturbance (e.g. diarrhoea, because it alter the bacterial flora in the gut)
35
Q

Clarithromycin

A
  • A macrolide antibiotic
  • Highly active on H. pylori.
  • More acid-stable and more active than erythromycin.
  • A key component in many treatment regimens.
  • growing prevalence of clarithromycin resistance - compromising success rates of clarithromycin-containing regimens in recent years

Side effects:

  • Hypersensitivity reactions (rash, fever, anaphylactic shock)
  • Gastrointestinal disturbance (e.g. diarrhoea) because it alter the bacterial flora in the gut
36
Q

Bismuth Compounds

A
  • A topical antimicrobial.
  • Disrupts integrity of bacterial cell wall. Prevents adhesion to gastric epithelium.
  • Inhibits bacterial urease, phospholipase, and protease
  • Two commercially available preparations:
    i) Bismuth subsalicylate (Pepto-Bismol)
    ii) Tripotassium dicitrato bismuthate (DeNol)
  • Newer formulation consisting of bismuth subcitrate potassium, metronidazole, and tetracycline in the same capsule:
    i) Bismuth- metronidazole- tetracycline (Pylera)
37
Q

Ranitidine bismuth citrate

A
  • Formed by reaction of ranitidine with bismuth citrate.
  • Higher solubility and antibacterial activity than an equimolar admixture of ranitidine and bismuth citrate.
38
Q

Netroimidazole

A
  • e.g. metronidazole, tinidazole
  • Highly active against H. pylori.
  • Well absorbed but actively secreted into gastric juice and saliva
  • pH-independent antibacterial activity.
  • Prevalence of resistance in Hong Kong: overall 29–39% in two local studies. Up to 71.4% in some years.
39
Q

Proton Pump Inhibitors

A
  • e.g. Omeprazole, esomeprazole, Lansoprazole, (Pantoprazole, Rabeprazole)
  • Some direct action on H. pylori.
  • Optimizes intragastric pH for other antibiotics.
  • Suppresses but does not eradicate the organism when given alone in vivo
40
Q

Eradication regimens

A

1) Triple therapy (PPI-based)
2) Triple therapy (bismuth-based)
3) Ranitidine bismuth citrate-based therapy
4) Quadruple therapy and second- / third-line treatment
5) Sequential therapy

41
Q

Triple therapy (PPI-based)

A

PPI + clarithromycin + amoxicillin or metronidazole

  • Duration of treatment: 10–14 days (higher efficacy than 7 days).
  • Lower eradication rates in the presence of antibiotic resistance (especially clarithromycin)
42
Q

Triple therapy (bismuth-based)

A

Bismuth + metronidazole + amoxicillin or tetracycline

  • Most failures due to metronidazole resistance.
  • Metronidazole resistance: substitute with clarithromycin or azithromycin.
43
Q

Ranitidine bismuth citrate-based therapy

A

1) Ranitidine bismuth citrate + clarithromycin.

2) Ranitidine bismuth citrate + clarithromycin + amoxicillin.

3) Ranitidine bismuth citrate + clarithromycin + metronidazole.

[Ranitidine bismuth citrate may not be available in some countries. Not registered in Hong Kong as of February 2014]

44
Q

Quadruple therapy and second- / third-line treatment

A

1) PPI + bismuth + two antibiotics (e.g. tetracycline + metronidazole or amoxicillin + clarithromycin).

2) PPI + three antibiotics (e.g. amoxicillin + nitroimidazole + clarithromycin).

3) Levofloxacin- or moxifloxacin-based regimens (when there is resistance to other antibiotics)

[Antibiotic susceptibility testing is essential for patients who failed the initial standard regimens]

45
Q

Sequential therapy

A

5 days of PPI + amoxicillin; followed by 5 days of PPI + clarithromycin + nitroimidazole.

46
Q

Selection of eradication regimen

A

consider:

1) efficacy
2) side effects
3) cost
4) compliance
5) antibiotic resistance
6) adverse drug interaction.

47
Q

Who needs eradication?

A

Guidelines exist on the indications for treatment, e.g. the Maastricht IV / Florence Consensus Report. Main indications include the following patients with a positive test for H. pylori:

1) Peptic Ulcer Disease (Duodenal ulcer, gastric ulcer)
2) Gastric MALT lymphoma.
3) Non-ulcer dyspepsia.
4) Chronic users of NSAIDs

Gastrointestinal Block (24 decks)

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