Pathology of TB Flashcards

1
Q

What is the aetiology of TB?

A
  • 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)
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2
Q

What are risk factors of TB?

A
  • 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)
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3
Q

What is TB latent infection?

A
  • 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
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4
Q

What is TB disease?

A
  • 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
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5
Q

How is TB diagnosed?

A
  • Skin test
  • Microbiological sampling
  • Blood Test
  • Molecular Testing
  • Imaging
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6
Q

What is skin testing (TB)?

A
  • 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
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7
Q

What is microbiological sampling in TB?

A
  • 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
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8
Q

What is ziehl neelsen staining?

A
  • 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
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9
Q

What are interferon-gamma release assays?

A
  • 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
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10
Q

What is molecular testing (NAAT) in TB?

A
  • 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
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11
Q

What is imaging in TB?

A
  • 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

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12
Q

What is the signs and symptoms of TB?

A
  • 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

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13
Q

What is a granulomatous inflammation in TB?

A
  • 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
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14
Q

What are the TH1 cells in TB?

A
  • 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
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15
Q

What are the TH2 cells in deisease in TB?

A
  • 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
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16
Q

How is TB transmitted?

A
  • 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
17
Q

What is the pathogenesis of TB?

A

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

18
Q

What is Ghon Focus and Ghon complex?

A

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.

19
Q

What is TB with cavitation?

A

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

20
Q

What is the spread of TB?

A

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)

21
Q

What is miliary TB of lung and Spleen?

A
  • 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
22
Q

Compare immunocompetent and immunocompromised Primary TB?

A

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

23
Q

Compare immunocompetent and immunocompromised secondary TB?

A

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