Pathology of Tuberculosis PDF

PATHOLOGY OF TUBERCULOSIS Dr Marie Kokolski AETIOLOGY • Tuberculosis is caused by an infection with Mycobacterium tuberculosis • Obligate aerobe, rod shaped bacteria spread mostly through airborn droplets and dust micro particles • Acid fast • Slow rate of growth • Sensitive to heat and UV radia...

PATHOLOGY OF TUBERCULOSIS Dr Marie Kokolski AETIOLOGY • Tuberculosis is caused by an infection with Mycobacterium tuberculosis • Obligate aerobe, rod shaped bacteria spread mostly through airborn droplets and dust micro particles • Acid fast • Slow rate of growth • Sensitive to heat and UV radiation • Non-motile • Likes highly oxygenated tissue TB INFECTION • Not everyone infected with TB bacteria develops the clinical disease • As a result, two TB-related conditions exist: latent TB infection and TB disease. Latent infection: TB disease - No signs or symptoms - Host defences prevent growth of bacteria - Not infectious, cannot pass infection on - Skin or blood test positive - Normal chest X-ray - 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 Xray or sputum sample - Needs treatment ZIEHL NEELSEN Mycobacteria have the unusual property of retaining basic dyes when treated with acidic solutions. This property is a consequence of the mycobacterial envelope, which contains waxes composed of long-chain branched hydrocarbons. The most abundant wax, mycolic acid, is an α-alkyl-hydroxy fatty acid covalently linked to the cell wall. The name Mycobacteria reflects the presence of mycolic acid in the organisms. The waxy barrier greatly reduces permeability to many molecules, including Gram stain, and mycobacteria are neither Grampositive nor Gram-negative BLOOD TESTS - INTERFERON-GAMMA RELEASE ASSAYS (IGRAS) QuantiFERON®-TB Gold In-Tube test (QFT-GIT) or T-SPOT®.TB test (TSpot) White blood cells from infected persons release IFN-g upon exposure to antigens derived from M. tuberculosis ­ Rapid testing (approx. 24 hours) and BCG vaccination does not affect results ­ Blood samples must be stored and processed correctly ­ Limited data on progression to TB disease ­ Limited data on use in children under 5, immunocompromised, persons recently exposed to M. tuberculosis ­ Expense MOLECULAR TESTING - NAAT Rapid diagnostic nucleic acid amplification test (NAAT) • Many types available • Can diagnose the specific Mycobacterium (tuberculosis, bovis, africanum) and resistance to front line drugs • Very expensive NICE guidelines – Request if there is clinical suspicion of pulmonary TB disease, and: the person has HIV or rapid information about mycobacterial species would alter the person's care or the need for a large contact-tracing initiative is being explored. SYMPTOMS • Primary stage is asymptomatic/mild flu symptoms • Reactivated: (may take months to appear) 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 cavitation occurs, haemoptysis • Systemic: many-local to infection e.g. headache and neurological deficit in brain metastasis, swelling in neck if lymph involvement GRANULOMATOUS INFLAMMATION • A form of chronic inflammation characterised by groups of activated macrophages, T lymphocytes and sometimes necrosis • It is the body’s attempt to section off an offending agent that is difficult to eradicate – the attempt to eradicate is often damaging to healthy tissue • Activated macrophages can begin to resemble epithelial cells – epithelioid cells • Some macrophages fuse together to form Langhans giant cells GRANULOMATOUS INFLAMMATION • Older granulomas have fibroblasts and collagen • Hypoxia causes necrotic core • In TB ONLY: caseous necrosis; yellow-white cheese-like (gross) amorphous granular lysed cells with no cell outlines/architecture. • Seen in few diseases: TB, leprosy, cat scratch disease, syphilis, sarcoidosis, Crohn's disease TRANSMISSION Exposure to persons with active TB disease 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 PATHOGENESIS First 3 weeks: • Inhaled mycobacteria engulfed by macrophages • Manipulate endosomes (pH and maturation) • Defective phagolysosome formation • Mycobacterial proliferation in macrophages • Mild flu symptoms/ asymptomatic • Resistance of organism • Hypersensitivity of host • 95% will heal • Cell mediated immune response • Macrophages drain to lymph nodes • Antigens presented to T cells • T cells converted to Th1 cells • Th1 cells activate macrophages (gamma IFN) • Monocytes recruited free radicals and ROS • Epithelioid macrophages GHON FOCUS AND 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. 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 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) MILIARY TB OF LUNG & SPLEEN • John Jacob Manget 1700 - based on how appearance in autopsy findings • 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 miliary TB - a very serious, lifethreatening illness • Seeds expand, coalesce and destroy large areas of organ TB SUMMARY Secondary TB Primary TB (exogenous) Immunocompetent Immunocompromised 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 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 (reactivated/endogenous) Immunocompetent Immunocompromised Apical lesion of caseating granuloma. Immune response activated and healing by fibrosis Not lymph nodes Apical lesion enlarges: large mass with little collagen Increased risk of erosion into vasculature/bronchi Bronchus: Tuberculous bronchopneumonia. Live bacilli in sputum: open TB Vessel: miliary or isolated organ TB KEY POINTS - MYCOBACTERIUM TUBERCULOSIS This agent infects one-third of the world's population, but only 10% of those infected develop clinical disease. The bacterium is usually acquired by inhaling aerosolized droplet nuclei. ØM. tuberculosis can cause illness that begins soon after initial infection (primary disease) or can remain latent for years before reactivating and causing illness (endogenous reactivation). ØInfection may elicit a cellular immune response that controls infection, with the only sequelae being a positive tuberculin skin test. Or, ØInfection may elicit a host immune response responsible for the pathologic features of the disease. Active tuberculosis (TB) most often causes pulmonary disease associated with fever, weight loss, and drenching night sweats. ØTB is usually diagnosed by microscopy and culture of sputum. ØTB is more risky for those who are immuno-compromised (HIV