9. Helicobacter Plyori Flashcards
How prevalent is H. pylori infection?
What are its main symptoms?
- Present in 50% of world population Symptoms of infection: - Gnawing or burning abdominal pain - Loss of appetite/weight loss - Malaise - Halitosis (bad breath) - Bloating - Burping - Nausea - Acid Reflux
What are the clinical outcomes of a H. pylori infection?
- 80% = Gastritis (inflammation of stomach):
- Can be asymptomatic or chronic and symptomatic - Chronic atrophic gastritis (breaking down of stomach lining) and intestinal metaplasia (gastric cells become like intestinal cells)
- 20% = Gastric or duodenal ulcer (peptic ulcer disease)
- <1%: Gastric cancer and MALT lymphoma
How does the anatomy of the stomach relate to the pattern of H. pylori ulcer disease?
- Parietal cells of the fundus (top of stomach) secrete acid
Atrial-predominant:
If a person naturally produces a lot of acid:
- H. pylori will colonise in the antrum (bottom of stomach)- causing a greater predisposition to duodenal ulcers
- The antrum will subsequently get inflamed which will trigger G cells to produce gastrin which causes parietal cells to secrete more acid
- Gastric histology: chronic inflammation, polymorph activity
- Duodenal histology: gastric metaplasia, active chronic inflammation
Pan-gastritis:
If a person does not produce as much stomach acid:
- H. pylori will colonise right throughout the stomach
- The entire stomach gets inflamed which increases the susceptibility to gastric ulcers and gastric cancers
- Acid secretion is reduced
- Gastri histology: chronic inflammation, atrophy and intestinal metaplasia
- Causes gastric ulcers and gastric cancer
What bacterial factors affect H. pylori pathogenicity?
- The cag pathogenicity island (cag PAI)
- Associated with more severe disease (increased risk of duodenal ulcer and gastric cancer)
- CagAis an immunodominant antigen protein encoded by the cag PAI
- The Cag PAI also encodes the type IV secretion system: responsible for delivery of CagA into host cells
What host factors affect H. pylori pathogenicity?
- IL-1B and TNF polymorphisms in host gene increases gastric cancer risk
- H. pylori CagA+ strains interact with host epithelial cells in stomach (get in with type IV secretion factor) and induce a pro-inflammatory signalling response resulting in IL-8 production
- Once secreted from the epithelial cells, IL-8 attracts neutrophils and monocytes to the area
- These neutorphils and monocytes upregulate the expression of IL-1B and TNF-a which act on parietal cells to decrease cell acidity
- This increases risk of gastric cancer
How is H. pylori transmitted?
- Natural H. pylori infection is restricted to human
- Transmitted via close person-to-person contact (infections mostly occur within families)
- H. pylori is fragile so requires quick person-to-person contact via gastric contents
- 3 potential routes:
1. Gastric-oral (vomit, reflux)
2. Oral-oral (oral cavity)
3. Faecal-oral (diarrhoea)
How is duodenal ulcer disease managed?
- Modern therapy: Combination therapy of 2-3 antibiotics alongside a PPI allows for ulcer healing and cure
- Original treatment included only PPIs, antacids and even surgery which was not infection as ulcers would heal and then relapse because causative agent H. pylori is still present
What are the morphological features of H. pylori?
- Gram negative spirochete
- 2-6 sheathed polar flagella
- Microaerophilic (2-6% O2)
- Grows inblood or serum containing complex media e.g. HBA
- Grows at 37 degrees and pH 5.5-8
- Catalase negative
- Oxidase negative
- Urease positive
What are the two different mophologies of H. pylori
- Can exist in spiral and coccoid shape
- Conversion of spiral to cocoid is triggered by starvation, oxidative and acidic stress and antibiotics (no conversion back to spirochete)
- Two subtypes of cocoid exist:
1. Viable and biologically active: cannot be cultured, have an intact cell wall and structures and a flagella wrapped body
2. Degenerative form: have disintergrated membranes and are a result of cell death
What are the features of the coccoid morphology of H. pylori?
- Proteins in cell division, transcription and translation, chemotaxis and pathogenicity are down regulated
- Outer membrane proteins are up-regulated
- Modifications of peptiodoglycan wall allow for immune evasion
What are the major virulence factors of H. pylori that help make it a permanent coloniser of the human stomach?
- Urease- colonisation factor
- Flagella- colonisation factor
- Can undergo chemotaxis- colonisation
- Has many adhesins- colonisation
- Can persist
- Has outer membrane vesicles
What are the functions of urease?
- A large multimeric nickel-containing protein
- Encoded in operon of 7 genes: ureA and ure B (structural) and ureE-I (functional)
- Catalyses hydrolysis of urea into carbonic acid and ammonia thus neutralising stomach acid (but damaging mucosal surface)
- Required for H. pylori to move through highly acidic gastric juice and mucous layer of stomach to reach gastric mucosa
- Acts as a releasable decoy that binds hot immunoglobulins
What is the function of H. pylori flagella?
- H. pylori use 2-6 polar flagella to burrow into the mucous lining of the stomach so it can colonise the gastric mucosa
What is the function of chemotaxis?
- Chemotaxis: movement of an organism in response to chemical stimulus
- H. pylori chemotaxes in response to urea, bicarbonate, mucin and amino acids (also uses pH gradient to provide spatial orientation toward epithelium)
- Many proteins are involved: CheA and CheY (change direction of motor rotation) and TIpB (chemoreceptor- detects urea)
What are the H. pylori adehsins?
- There are multiple adhesions involves in the adhesion of H. pylori to epithelial cells
e. g. BabA (blood group antigen binding adhesin)- - mediats strong binding to blood group antigen oon surface of epithelial cells and in gastric mucus
e. g. SabA (sialic acid binding mechanism)- mediats weaker binding to siacylated Lex antigens (that are up regulated during inflammation) - can be turned on and off to avoid WBCs
e. g. Various other OMPs (outer membrane proteins) such as AlpA/B
