Tuberculosis


Risk factors:

  • immunosuppression

  • Homelessness

  • Birth in an endemic country


Most endemic countries to TB:

  • India

  • China

  • Indonesia

  • The Philippines

  • Pakistan

  • Nigeria

  • Bangladesh

  • South Africa


2 phases of TB

  • latent

  • Active


Latent TB::

  • individuals who are infected but have no active disease, no symptoms and are not infectious


Active TB:

  • individuals who are symptomatic and have the progressive disease


Mycobacterium tuberculosis:

  • bacterium that causes TB

  • Gram positive bacillus

  • Gram stain - doesnt hold the stain well, acid fast bacilli

  • Resistant to decolourisation of staining by acid

  • Use ziehl-neelsen stain - turns bright red if present


4 types of mycobacterium capable of causing TB:

  • mycobacterium tuberculosis - only humans can host

  • Mycobacterium bovis - cattle and other mammals

  • Mycobacterium africanum - seen in west Africa

  • Mycobacterium microti - other mammals

  • Called mycobacterium complex


Mycobacterium growth:

  • require oxygen to grow

  • Obligate aerobes

  • Can grow extracellularly

  • Advantageous to grow intracellularly - facultative intracellular


Initial inhalation of MT:

  • Infection either cleared straight away - breathed back out

  • Or primary TB


Primary TB:

  • infection present but suppressed by immune system

  • Asymptomatic

  • Can lead to progressive-primary TB and latent TB


Progressive-primary TB:

  • primary infection is not suppressed

  • Prolonged infection occurs


post primary TB:

  • progresses from latent TB

  • Also called reactivation

  • Usually due to immunocompromisation

  • Can be caused by infliximab (for rheumatoid arthritis and IBD)


Inhalation at microscopic level:

  • it can evade mucociliary escalator

  • Though bronchioles and into alveoli

  • Usually into middle and lower lobes first


TB in alveoli:

  • usually would be engulfed by dust cells and then digested by lysozymes

  • TB inhibits lysozymes and proliferates

  • Causes primary TB

  • Critical mass of TB in lungs triggers cell-mediated immune response

  • CORD factor on TB stimulates alveolar macrophages



Immune response:

  • TB is exogenous pathogen

  • Class II MHC activated

  • CD4+ cells activated from class II MHCs

  • Interferon gamma released from CD4+c cells

  • Interferon gamma stimulates macrophages to secrete tissue/tumour necrosis factor

  • Macrophages: encircle a group of TB, inside dies and becomes necrotic, outside stays alive, small caseating granuloma (ghon focus - looks like cheese)


Ghons complex:

  • When TB spreads to lymphatic system, network of ghon foci develops in lungs and lymphatics

  • When calcified, called ranke complex

  • If infected persons immune system becomes compromised, TB can be reactivated and complex no longer maintained


how TB spreads:

  • goes to upper lobes first because most o2 concentrated

  • Lesions in upper lobes form

  • Can spread bronchogenic, lymphatic or circulatory

  • Bronchogenic spread causes bronchopneumonia

  • Lymphatic spread causes swelling in cervical nodes - scrofula

  • Miliary TB is when it spreads through the blood

  • You’ll see millet seeds on X-ray with miliary TB


5 main places TB spreads to via blood:

  • kidneys - causes elevated WBC in urine

  • Meninges - causes meningitis

  • Lumbar vertebrae - causes Potts disease (lower back pain, microfractures and inflammation)

  • Liver - causes hepatitis

  • Adrenal glands - causes addisons disease (affects sex steroids, catecholamines, mineralocorticoids)


Symptoms of pulmonary TB:

  • fever

  • Nightsweats

  • Haemoptysis

  • Unplanned weight loss

  • Could have SOB


Diagnosing TB:

  • skin or blood test

  • Chest x ray


Mantoux test:

  • main skin test used

  • Intradermal injection of tuberculin

  • If patient has had TB will have type 4 hypersensitivity reaction

  • Previous BCG vaccination can interfere with test


Interferon gamma release assay:

  • IGRA is blood test used

  • Tests for the bodies cellular immune response to TB so tests whether person currently has it


Chest xray:

  • sputum samples taken alongside

  • Look for lesions


Treatment for latent TB:

  • isoniazid for 9 months


Treatment for active TB:

  • must quarantine for 2-3 weeks

  • For drugs mnemonic: RIPE

  • Rifampicin, isoniazid (+pyridoxine), pyrazinamide, ethambutol

  • R - inhibits RNA polymerase and hence bacterial RNA synthesis

  • I - inhibits mycolic acid synthesis, side effects can include peripheral neuropathy which is pins and needles but pyridoxine prevents it

  • P - inhibits cell wall synthesis

  • E - side effects include red green colour blindness

  • All these drugs are given at once to decrease chances of TB becoming resistant


First line treatment for active TB:

  • RIPE for 2 months

  • RI for a further 4 months


First line treatment for latent TB:

  • I for 6 months

  • OR RI for 3 months