Pathogenesis of TB Flashcards
What is TB caused by?
Mode of transmission?
Infectious dose?
Mycobacterium Tuberculosis
Contagious - via AIRBORNE DROPLETS
1-3 bacilli
TB symptoms?
Persistent cough
- initially mild - non productive
- turns into productive
- haemoptysis
Fatigue
Weight loss
Appetite loss
Fever
Night Sweats
Dyspnoea
Multi-organ dysfunction/adrenal insufficiency
STAGES of TB
Active vs Latent
Exposure
infection - which can progress or become latent
Active disease - can become latent with treatment/remission
Latent disease can reactivate - due to immunosupression (HIV)
Latent TB infection
symptoms?
spread?
skin test/IGRA results?
CXR results?
Sputum results?
Culture results?
No symptoms
Cannot spread to others
positive skin test or IGRA
Normal CXR
Negative sputum
Negative culture
No treatment
Active TB
Symptoms?
Skin Test / IGRA result?
CXR findings?
Sputum results?
Culture?
Treatment required?
Symptoms present
Can spread to others
Positive skin test and IGRA
Abnormal CXR
Positive Sputum smear
Culture Positive
Requires treatment
Risk factors for reactivation?
Malnutrition
Immunosuprresion
Diabetes
Old age
Poor Health
HIV
The link between HIV and TB
HIV - increased rate of reactivation of TB x 20 fold
Progression to AIDs is MORE RAPID
sites of infection in TB
75% pulmonary TB
25% extra pulmonary TB
HAEMATOGENOUS SPREAD
- pleural disease
- lymph nodes
- pericardial
- skeletal (potts disease)
- genitourinary
- gut
- peritoneal
- miliary
- meningeal
Stages in pathology
Inhalation of M.Tuberculosis
- upper region of LOWER LOBE of lung - LESION produced - GHON FOCUS
- lymphangitic spread from the ghon focus
- granulomatous involvement of PERIBRONCHIAL / HILAR LYMPH nodes
- ghon focus + lymph node lesion = GHON COMPLEX = (CASEOUS NECROSIS)
- lesions undergo HEALING and overtime evolve to fibro-calcific nodules
When does miliary TB occur?
Who does it affect ?
post primary infection/reactivated TB - when resistance to mycobacterial infection is POOR
Tubercles = granulomatous formation
Often seen in CHILDREN - after primary disease
What is intestinal TB
Causes:
Primary?
Secondary?
Primary intestinal TB - people who drink milk infected with M.Bovis
when you swallow INFECTED SPUTUM - leads to secondary intestinal TB
Meningeal TB
Appearance?
Where are small tubercles present?
Common complication of?
Rarely seen in?
Thickened and opaque meninges
Tubercles are present IN THE BRAIN
Common - children with post primary miliary TB
Those with BCG vaccination
Potts disease due to TB?
haematogenous spread of TB - (blood stream) - lodge in the bone marrow of the vertebrae and intervertebral discs
Caseous necrosis - infected tissues DIE and form dry soft tissue mass
Scrofula secondary to TB
Extra pulmonary haematogenous spread - into lymph nodes in the NECK
immunopathology of TB - how is the immune system involved in a BAD way ??
Hypersensitivity type 4 - cell mediated
- CD4+ cells are ACTIVATED - EXCESSIVE
- overproduction of TNFa - leads to macrophages being drawn to location
- healthy tissue damage by macrophages - granuloma formation
How is the immune system involved in a GOOD way?
Innate immunity - macrophages in alveoli KILL ingested bacteria
Th1 - adaptive immune response = CB8 and CD4 T cells - IFN gamma (vascular endothelium activation) - ESSENTIAL FOR CONTROLLING INFECTION
Are myobacterium intracellular parasites?
mechanisms of evading immunity?
Yes - they hide inside the macrophages when they are ingested
They escape into the cytoplasm (avoid phagolysosome)
They INHIBIT phagolysosome fusion, maintain the early endosome and block acidification
They control antigen presentation and DOWNREGULATE recruitement of Cytotoxic killer T cells and BLOCK macrophage activation
What function is granuloma formation ?
What is the consequence of granuloma formation?
How long does it take for tissue damage?
What cells are involved?
containment of infection - but it leads to tissue damage
2-4 weeks
WBC and macrophages
Centre of granuloma - liquefaction, coagulative necrosis = caseous necrosis
What are granulomas formed of?
Infiltrating cells (neutrophils, macrophages, lymphocytes)
Surround the INFECTED cells
Persistent TB bacteria
FOAMY MACROPHAGES
What type of hypersensitivity reaction is TB ?
Type 4
delayed type hypersensitivity
What happens with liquefaction of granuloma and cavitation?
transmission - mycobateria are freed during liquefaction
What diagnostic tests are done for TB?
Blood test - IFN gamma blood test (T cell response to Mtb)
CXR - look for caseous necrosis - ghon complex
Sputum: smear, culture, PCR
Bronchoscopy - BAL
Biopsy
What stain is used for TB
Ziehl Neeson stain
auramine stain
Mantoux test is used for?
PPD is injected to see if individual has been EXPOSED to TB
