Tuberculosis Flashcards
Describe the pathologenesis of TB
Mtb can affect every organ of the body but has tissue trophism for the lung.
Ingested by alveolar macrophages but escapes from the phagolysosome to multiply in the cytoplasm.
Mycolic acid and other lipids result in granuloma formation and resist host cell oxidative response.
Intense immune response causes local tissue destuction, resulting in cavitation in the lung.
Production of cytokines produce systemic effects: fever, and weight loss
Describe the primary and post-primary response to TB
Primary TB: primary complex with lesion and draining gland. Usually asymptomatic. Skin test conversion.
Progressive primary disease: haematogenous, lymphatic or local spread
Post-primary TB: reactivation of quiescent disease.
Local spread - pneumonia
haematogenous spread - miliary
How does the cell wall of mycobacterial cell wall influence pathogenicity?
Hydrophobic lipid cell envelope
Provides resistance to many antibiotics
resistance to killing by acidic and alkaline compounds,
resistance to complement lysis
resistance to oxidative burst and persistence in Macrophages
Describe the Mantoux test and its use
TB causes an infected type IV hypersensitivity reaction
Killing is mediated by T cells and activation of macrophages. Which mount an antibody response.
Intradermal injection with tuberculin causes a local reaction in the skin with the development of an inflammatory nodule.
Positive mantoux indicates exposure to TB
Clinical presentation of TB
Classical symptoms:
Night sweats, mild chonic cough with purulent sputum, fever, dyspnoea, bronchopneumonia
Clinical features vary dependent on the extent, stage and activity of disease
Miliary TB
Uncontrolled haematogenous dissemination due to primary progressive infection or reactivation. Visible as multiple nodules on CXR
Granuloma enlarges and ruptures into the airway which allows it to become widely disseminated. Causes numerous small granulomas in many organs e.g. kindeys, bone, liver, GIT
Occurs in impaired immunity e.g. infants, HIV
Acute medical emergency
How is TB diagnosed?
Clincal presentation
Chest X-ray
Staining: Ziehl-Neelsen or auramine
PCR or NAATs
IFNg Release Assay
Culture and sensitivity
Management of TB
Initial 2 month regime of rifampicin, isoniazid, pyrazinamide and ethambutol
4 months of rifampicin and isoniazid
Regular follow up required due to lack of compliance. DOTS short course should be used to imptove compliance.
Treatment may need to be prolonged if organism is resistant to drugs, patient is inolerant of drugs, site of infection means there is a slower response.
Presentation of TB on CXR
Consolidation at the apex of the lung (with cavitation)
Fibrosis or calcificaiton (scarring from previous disease)
Pleural effusion
Histological appearance of TB lesion
Central zone of caseous necrosis surrounded by epitheliod macrophages, giant cells and lymphocytes.
The infection may progress with systemic spread > death
In most cases, the primary lesion will organise and heal as the immune reaction to the organism develops, leaving a fibro-calcified nodule.
Gohn focus
Reaction at the site of the initial infection in the lung parenchyma.
Primary focus with tubercular hilar adenopathy/infection is a Ghon complex
IFNg release assay in TB
Can be used to detect TB infection.
T-cells release IFNg when exposed to TB antigen. WBCs are taken from the patient and mixed with antigens to test for IFNg release.
Do not get a false positive result if patient has had prior BCG
Mechanisms of drug resistance in TB
Arises from spontanous low frequency chromosomal mutations.
Inadequate treatment or poor adherenece produces a selection advantage for resistant mutants which rapidly multiply
Sites of extrapulmonary TB
Meningitis
Kidneys
Bone: lumosacral spine, causes vertebral collapse, nerve compression, psoas absess
Joints
GIT: malabsorption and peritonitis.
