Pathology of TB Flashcards
What is the aetiology of TB?
- Caused by an infection with mycobacteriumm tuberculosis
- Obligate aerobe, rod shaped bacteria spread mostly through air-born droplets and dust micro particles
- Acid fast - retain acid staining
- Slow rate of growth
- Sensitive to heat and UV radiation
- Non-motile
- Likes highly oxygenated tissue (lungs are ideal to establish infection)
What are risk factors of TB?
- People who have been recently infected with TB bacteria
- via close contact with someone with infectious TB disease
- People who have migrated from areas of the world with high rates of TB
- Children less than 5 years of age who have a positive TB test
- Groups with high rate of TB transmission, homeless, drug userm HIV infected people etc
- People who work alongside/ resude with ppl who are a high risk for TB in facillities / institutions such as hospitals, homeless shelters, nursing homes etc
- People with medical conditions that weaken the immune system (substance abuse . sillicosis , Diabetes melitus, kidney disease, low body weight, med treatments, organ transplants, corticosteroids , infection with HIV, cancer , hodgkin’s disease)
What is TB latent infection?
- No signs or symptoms of TB
- Not everyone infected devleops the clinical disease
- Not infectious, cannot pass infection on
- Skin or blood test positive
- Normal chest x-ray
What is TB disease?
- Primary infection or activation of latent TB
- Signs and symptoms, patient feels sick
- Can spread infection
- Skin or blood test positive
- May have abnormal chest X-ray or sputum sample
- Needs treatment
How is TB diagnosed?
- Skin test
- Microbiological sampling
- Blood Test
- Molecular Testing
- Imaging
What is skin testing (TB)?
- TST- Tuberculin skin test
- aka Mantoux test
- 0.1ml of tuberculin derived protein injected into skin of forearm
- Positive test = 5mm or larger
- Measure diameter of palpable, raised, harderned area or swelling (NOT erythema) at 48-72 hrs
What is microbiological sampling in TB?
- Sputum analysis
- Slender rods, aerobes
- High content of complex lipid- ID by acid fast stains
- Growth is slowed by acidic pH, prescence of long chain fatty acids, anaerobic conditions
- Cultures to check for drug susceptibility
What is ziehl neelsen staining?
- Mycobacteria can retain basic dyes when treated with acidic solutions
- Due to the mycobacterial envelopem which conttains waxes composed of long-chain branched hydrocarbons
- Most abundant wax = mycolic acid, a-alkyl- hydroxy fatty acid covalently linked to the cell wall
- Waxy barrier greatly reduces permeabilty to many molecules, incl. Gram stain
- mycobacteria netither gram pos or gram neg
What are interferon-gamma release assays?
- cytokine
- blood taken from patient and ELISA test run
- Can measure levels of this cytokine in the blood
- Limited data on progression to TB disease
- Limited data on use in children under 5, immunocompromised, persons recently exposed to M tuberculosis
- Expensive
What is molecular testing (NAAT) in TB?
- Rapid diagnostic nuclei acid amplification test (NAAT)
- Many types available
- Can diagnose specific mycobacterium and resistance to front line drugs
- Very expensive
Only requested if : - the perosn has HIV
‘- Rapid info about myobacterial species would alter the person’s care
Need for a large contact-tracing initiative is being explored
What is imaging in TB?
- Type of imaging depends on site-specific investigations
- Pulmonary TB - X-ray/ CT thorax
Other examples
- Pleural TB- X-ray/ Bronchoscopy
- Lymph node TB- Ultrasound/CT/MRI
- CNS TB-CT/ MRI
What is the signs and symptoms of TB?
- Active TB infection:
- Persistent cough
- Constant fatigue
- Weight loss
- Loss of appetite
- Fever
- Coughing up blood
- Night sweats
Latent TB = no symptoms
Primary stage = asymptomatic/mild flu symptoms
Reactivated : gradual onset of anorexia, weight loss, fever (low grade,remitting, night sweats)
Lung : Persistent cough lasting longer than 3 weeks. Sputum (mucoid then purulent) - containing bacilli if cavitaition occurs, haemoptysis
Systemic: Many- local to infection m headcache and neurological deficit in brain metastasis , swelling ub becj if lymph involvement
What is a granulomatous inflammation in TB?
- Form of chronic inflammation characterised by groups of acivated macrophages, T lymphocyes and sometimes necrosis
- Body’s attempt to section off an offending agent that is difficult to eradicate
- Often damaging to healthy tissye
- Activated macrophages can begin to resemble epithelial cells - epithelioid cells
- Some macrophages fuse together to form Langhans giant cells
- Older granulomas have fibrobalsts and collagen
- Hypoxia causes necrotic core
- In TB only : caseous necrosis, yellow-white cheese -like gross amorphous granular luysed cells with no cell outlines/architecture
- Seen in few diseases : TB, leprosym cat scratch disease, syphilis , sarcoidosis, Crohn’s disease
What are the TH1 cells in TB?
- M tuberculosis resides into alveolar macrophages - resistant to phagocytosis
- IFN-y and TNF-a from macrophages required for killing
- Granuloma formation:
- Macrophages surround mycobacteria
- TH1 cells surround macrophages (IFN-y)
- Prevents spread around the body
- CTLs involved in direct killing
What are the TH2 cells in deisease in TB?
- Upon infection, M tb resides into alevolar macrophages - resistant to phagocytosis
- TH2 cell cytokines promite antibody production
- Ineffective against intracellular bacteria
- M tb continues to replicate and spreads around the body - disseminated tb
- TH1 - pulmonary TB
- TH2 response = disseminated TB