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
How is TB transmitted?
- exposure to people with active TB diswease
- Infected persons can project high numbers of bacteria in cough
- Small droplets or aerosols containing the bacteria from coughs = inhaled and reach alveoli
- Waxy outer coating makes organism resistant to desiccation
What is the pathogenesis of TB?
3 weeks :
- Inhaled mycobacteria engulfed by macrophages
- Manipulate endosomes (pH and maturation)
- Defective phagolysome formation
- Mycobacterial proliferation macrophages
- Mild flu symptoms/asymptomatic
- Cell mediated immune response
– Macrophages drain to lymoh nodes
- Antigens presented to T cells
- T cells converted to Th1 cells
- T h1 cells activate macrophages (gamma IFN)
- Monocytes recruited free radicals and ROS
- Epithelioid macrophages
What is Ghon Focus and Ghon complex?
Ghon Focus & Ghon Complex
Ghon Focus
Primary lesion of granulomatous inflammation
Usually subpleural
Ghon Complex (primary complex)
A Ghon focus & infection of adjacent lymphatics and hilar lymph
nodes
When a Ghon’s complex undergoes fibrosis and calcification it is
called a Ranke complex
The primary complex usually resolves within weeks or months, leaving signs of fibrosis and calcification
detectable on chest X-ray. In general the risk of disease progression following primary infection is low, but young children and immunocompromised patients are at increased risk.
What is TB with cavitation?
TB with Cavitation
* If the immune system of the
person with a TB granuloma
deteriorates, these bacteria can
be reactivated and TB may
break out again
* Once the TB bacilli become
reactivated, they rapidly
destroy the lung tissue around
the granuloma. This causes
major damage to the tissue,
which gets destroyed
What is the spread of TB?
Spread of TB
* Caseating tubercle erodes into lung
vasculature
* Systemic dissemination to any organ via
pulmonary vein (commonly liver, kidney,
spleen)
* If pulmonary artery involved (ie lymph
drainage to right heart): miliary TB of lung
* Isolated organ (metastatic) TB: If few
organisms invade the blood stream they are
dealt with or can remain latent in an organ
for years (eg brain, kidney, adrenals)
What is miliary TB of lung and Spleen?
- The bodies would have a lot of very small
spots similar to hundreds of tiny seeds
about 2mm long, in various tissues. - Since a millet seed is about that size, the
condition became known as miliaryTB - a
very serious, life-threatening illness - Seeds expand, coalesce and destroy large
areas of organ
Compare immunocompetent and immunocompromised Primary TB?
Primary TB
(exogenous)
Secondary TB
(reactivated/endogenous)
Immunocompetent
Primary lesion is
subpleural caseous
granuloma: Ghon focus
Caseating hilar lymph
node involvement: Ghon
complex
Heals by fibrous
encapsulation. Latent TB
in tubercle
Resistance of organism
and hypersensitivity of
host. Few symptoms
Immunocompromised
Primary progressive TB
Enlargement of caseation of
lymph nodes: erodes into
bronchial wall or vessel
Bronchus: Tuberculous
bronchopneumonia (lower
lobes; galloping
consumption)
Vessel: miliary or isolated
organ TB
Compare immunocompetent and immunocompromised secondary TB?
Immunocompetent
Apical lesion of caseating
granuloma. I mmune
response activated and
healing by fibrosis
Not lymph nodes
Immunocompromised
Apical lesion enlarges:
large mass with little
collagen
I ncreased risk of erosion
into vasculature/bronchi
Bronchus: Tuberculous
bronchopneumonia. Live
bacilli in sputum: open TB
Vessel: miliary or isolated
organ TB
