Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
50 Cards in this Set
- Front
- Back
|
H Pylori is a ______________ helical shaped microbe |
gram negative |
|
|
How is H pylori transmitted? |
acquired in childhood through fecal-oral or oral-oral routes |
|
|
How does H pylori survive in the stomach? |
Urease that can buffer the local environment by production of ammonium from urea |
|
|
Where does H pylori colonize? |
Mucus layer and epithelial surface of the stomach and adheres to the epithelium through multiple outer membrane proteins |
|
|
How does H pylori evade immune mechanisms? |
Vacuolating toxin that suppresses T cell responses |
|
|
__________ causes cell death of the gastric epithelium |
VacA |
|
|
_____________ disrupts tight junctions between cells |
CagA |
|
|
Low level inflammation within the gastric mucosa leads to persistent _______________ |
superficial gastritis |
|
|
H pylori may cause _________________, which is a well established risk for gastric adenocarcinoma |
atrophic gastritis
|
|
|
Diagnosis of H pylor |
Raid urease test. histology, microbial culture Urease breath test Biochemical includes tests for urease, catalase, oxidase Testing stool for antigen is highly accurate |
|
|
Tx of H pylori |
Triple therapy - two antibiotics - proton pump inhibitor |
|
|
Histology chronic gastritis shows_________ |
elevated numbers of neutrophils and mononuclear cells in the lamina propria and the glandular epithelium in addition to lymphoid follicle |
|
|
Diseases H pylori can lead to |
Gastric and duodenal ulceration gastric adenocarcinoma mucosa associated lymphoid tissue lymphoma non-Hodgkin lymphoma |
|
|
Clinical outcomes of H pylori |
-Normal gastric mucosa - Superficial gastritis - Chronic gastritis - Asymptomatic state - Hyperacidity - gastric duodenal ulceration MALT/non Hodgkins lymphoma - Atrophic gastritis - Intestinal metaplasia - Dysplasia - Gastric adenocarcinoma |
|
|
H pylori is present in _______ of the worlds population |
half |
|
|
Risk factors for infection of H pylori |
Poor SES, familial overcrowding, ethnicity, and infection rates endemic to country of origin |
|
|
Premalignant lesions of H pylori |
intestinal metaplasia - early stage of gastric adenocarcinoma |
|
|
What factors determine the outcome of H pylori infection? |
strain specific virulence mechanisms determinents governed by genetic diversity of the host environmental factors |
|
|
H pylori produces ____________ that splits urea into ammonia and CO2 to neutralize the acidity of the stomach |
Urease |
|
|
How does H pylori overcome gastric peristalsis? |
efficient motility - polar flagella to penetrate gastric mucosa layer chemotaxis - colonize/persist in gastric niche 20% adhere to the gastric epithelial cells |
|
|
How does H pylori adhere to gastric epithelium? |
Outer membrane proteins: - Blood group antigen binding adhesin - BabA - binds to Lewis blood group antigen - Sialic acid binding adhesion, SabA - sialyl Lewis antigens |
|
|
What portions of H pylori are normally detected by the immune system? |
Flagella and LPS - Far less immunogenic than other species - much less endotoxin |
|
|
H pylori express Human lewis antigens on LPS that undergo _______________ |
phasic variation as a means of molecular mimicry to evade immune responses
|
|
|
______________ can modulate the immune response by suppressing T lymphocytes |
Vacuolating cytotoxin A |
|
|
H pylori induces a low grade, persistent inflammation within the gastric mucosa that leads all infected individuals to develop ______ |
superficial gastritis - majority develop asymptomatic chronic gastritis - 10% of individuals develop ulcers |
|
|
Inflammatory process associated with loss of epithelial glands over the course of several decades |
Atrophic gastritis - well established risk factor for gastric adenocarcinoma and MALT lymphoma |
|
|
Gastric cancer remains the ____________ leading cause of cancer related worldwide and H pylori remains the strongest known risk factor |
second |
|
|
Cytotoxin associated gene (cagA) is encoded by ____________ |
cag pathogenecity island - cagA is translocated into host epithelial cells following H pylori attachment and is modified by phosphorylation of tyrosine residues |
|
|
cagA possesses a __________ secretion system |
type IV - delivers bacterial effector proteins into cells |
|
|
Effects of CagA |
Disruptions of junctional complexes - tight junctions - adherens junctions Cell motility and proliferation Present in 90% of patients with duodenal ulcers due to high degrees of inflammation |
|
|
What inflammatory cytokine is elevated in cagA+ strains? |
IL-8 |
|
|
Effects of VacA |
Present in all strains Associated with peptic ulcer disease and increased inflammatory infiltrates within gastric antrum Epithelial damage leading to apoptosis, however cagA inhibits VacA induced apoptosis Functions as a transmembrane pore allowing urease pH balancing activity of H pylori |
|
|
MOA of ulceration |
- H pylori infection - Increased inflammation - Increased proliferation - Decreased Somatostatin D cells - Increased gastrin secretion - Increased acid secretion - Duodenal metaplasia to gastric type - Ulceration |
|
|
Development of gastric adenocarcinoma |
Chronic superficial gastritis to chronic atrophic gastritis to intestinal metaplasia to dysplasia to invasive adenocarcinoma |
|
|
H pylori ____________ cellular proliferation while _________ rate of apoptosis within colonized tissue leads to oxidative DNA damage due to ROS and nitrogen free radicals |
Increases cellular proliferation Decreases rate of apoptosis |
|
|
___________ strains are associated with an increased risk for gastric adenocarcinoma |
cagA+ |
|
|
What host determinant can influence the development of gastric cancer? |
Hypergastrinemia - precedes development of atrophic gastritis Polymorphisms within human IL-B and TNFa are associated with increased inflammation |
|
|
Development of MALT/Non-Hodgkins |
T cells react with with H pylori antigens to produce inflammatory cytokines that drive uncontrolled growth and proliferation of B lymphocytes leads to malignant lymphomatous degeneration |
|
|
Gastric mucosa biopsy tests |
Urease - highly sensitive
Histology - very sensitive Culture - very sensitive |
|
|
Stains used in H pylori |
Giesma Steiner and Warthin-Starry stain |
|
|
Biochemical conformation tests of H pylori |
Urease, catalase, and oxidase positive - produces ammonia turning indicator red |
|
|
Noninvasive tests |
Serologic test (ELISA) - limited use in post treatment because titers fall gradually over a 6 month period Urea breath test - radioactive labeled carbon urea, breathed off as CO2 Stool antigen - HpSA detects presence of H pylori antigens - stool antigens rapidly decline after 5 days |
|
|
Triple Therapy |
PPI - 2x daily for 7-10 days Amoxicillin - 1 g twice daily for 7-10 days Clarithromycin - 500mg 2x for 7-10 days |
|
|
Quadruple therapy |
PPI 2x daily for 14 days Bismuth subsalicyclate 120 mg 4x daily 14 days Tetracycline 500mg 4x daily 14 days Metronidazole 250 mg, 4x daily, 14 days |
|
|
Sequential therapy |
PPI 2x daily for 10 days Amoxicillin 1x daily for first 5 days Clarithormycin/Metronidazole 2x daily for the next 5 days |
|
|
Resistance to H pylori Tx due to |
- rapidly developing bacterial resistance to metronidazole, quinolone, and macrolides
- reduced efficacy of certain drugs such as clarithromycin and arithromycin under acid conditions - patient non compliance owing to side effects or the burden of ingesting multiple meds over 7-14 days |
|
|
Successful eradication is stated as |
negative test for bacterium 4 or more weeks after completion of therapy |
|
|
Role of PPI's |
relieve ulcer symptoms and promote ulcer healing
pH is raised which increases efficacy of antibiotics |
|
|
H pylori is becoming increasingly resistant to ______________ |
metronidazole and clarithromycin First line - clarithromycin and amoxicillin Second line - clarithromycin and metronidazole |
|
|
Two tests to confirm eradication |
stool and urea breath test |
