Pathology of tuberculosis 2015 2016
Pathology of tuberculosis 2015-2016
Required book Robbins basic pathology 9th edition Chronic pneumonias tuberculosis Chapter 12 lung Page 493 499
    Required book      Robbins basic pathology 9th edition     Chronic pneumonias  tuberculosis     Chapter 12  lung     P...
Objectives By the end of the lecture you should be able to List the causative agents of TB Identify route of infection by the agent Classify TB into primary and secondary subtypes Identify the aetiology and pathogenesis of TB
Objectives By the end of the lecture you should be able to      List the causative agents of TB     Identify route of infe...
Tuberculosis Is a communicable chronic granulomatous disease caused by Mycobacterium tuberculosis It usually involves the lungs but may affect any organ or tissue in the body Typically results in caseating granulomas
Tuberculosis     Is a communicable chronic granulomatous disease caused  by Mycobacterium tuberculosis     It usually invo...
Tuberculosis Epidemiology It is a leading cause of death globally as it accounts for 6 of deaths worldwide Is the most common cause of death resulting from a single infectious agent The lung is the most common important clinical site of infection
Tuberculosis     Epidemiology     It is a leading cause of death globally as it accounts for    6  of deaths worldwide    ...
Tuberculosis Epidemiology Until the mid 1980s in the USA Western countries there was a decline in TB infection followed by rise in its incidence The incidence in Western population increased in Immunosuppressed persons in immigrants from high prevalence areas
Tuberculosis     Epidemiology     Until the mid 1980s, in the USA   Western countries there  was a decline in TB infection...
Tuberculosis predisposing factors Tb flourishes in case of poor population bad hygiene diabetes mellitus malignancies alcoholics in patients with chronic debilitating illness One of the most common predisposing factors to TB is HIV infected persons
Tuberculosis    predisposing factors     Tb flourishes in case of       poor population,     bad hygiene,     diabetes mel...
Tuberculosis Microorganism M tuberculosis hominis Responsible for most cases Transmitted by inhalation of infective droplets coughed or sneezed into the air from patients with active open PTB airborne or by exposure to contaminated secretions M bovis Transmitted by milk from diseased cows intestinal oropharyngealTB Rare M avium intracellulare Very low virulence rarely cause disease in normal hosts Cause disseminated infection in 10 30 of AIDS pts
Tuberculosis     Microorganism     M. tuberculosis hominis     Responsible for most cases     Transmitted by inhalation of...
Tuberculosis Routes of infection Respiratory tract Most cases are acquired by direct person to person transmission of airborne droplets with organisms from an active case to a susceptible host Oropharyngeal and intestinal TB contracted by drinking dairy milk contaminated with M Bovis rarely seen nowadays and usually in countries with tuberculous dairy cows and unpasturised milk Skin by inoculation Congenital by transplacental spread
Tuberculosis     Routes of infection     Respiratory tract   Most cases are acquired by direct person to person transmissi...
Natural history of TB infecion Getting Infection with M tuberculosis is different from developingTB disease Infection which is the presence of the organism may or may not cause clinically significant disease Viable organisms may remain dormant for decades until immunity is suppressed infection may then be reactivated to produce disease with clinical manifestations
Natural history of TB infecion     Getting Infection with M. tuberculosis is different from  developingTB disease.     Inf...
Develop resistance
    Develop resistance
Tuberculosis Pathogenesis The sequence of events pattern of host response following an infection depends on the state of host immunity and whether the infection represents a primary exposure to the organism or secondary reaction in an already sensitized host Primary infection with M Tuberculosis means TB infection in previously unexposed immunocompetent person Secondary infection with M Tuberculosis means TB infection in previously exposed or sensitized person
Tuberculosis - Pathogenesis    The sequence of events pattern of host response following an  infection depends on the stat...
Tuberculosis Pathogenesis Macrophages are the primary cells infected by M tuberculosis Inhaled M Tuberculosis is endocytosed by alveolar macrophages by binding through mannose receptors and complement receptors Live bacteria prevent phagolysosome fusion At this point the macrophages are na ve and unable to kill mycobacteria which multiply lyse the host cell infect more macrophages and through them reach the hilar lymph nodes
Tuberculosis - Pathogenesis     Macrophages are the primary cells infected by M.  tuberculosis.     Inhaled M. Tuberculosi...
Tuberculosis Pathogenesis At this early stage of primary tuberculosis
Tuberculosis - Pathogenesis    At this early stage of primary tuberculosis   3 weeks  in the  non-sensitized individual an...
Tuberculosis Pathogenesis
Tuberculosis - Pathogenesis
Tuberculosis Pathogenesis While later in infection the T lymphocytes helper 1 cells TH 1 cells immune response develops at about 3w post infection This TH 1 response activates macrophages to become bactericidal The immunologic reaction is called type IV hypersensitivity reaction or delayed hypersensitivity reaction
Tuberculosis - Pathogenesis     While later in infection, the T lymphocytes-helper-1  cells   TH-1 cells immune response d...
Tuberculosis Pathogenesis TH 1 response is stimulated by mycobacterial antigens draining to Lymph Nodes and presented by alveolar macrophages which produce IL 12 that causes the differentiation and Activation of TH 1 cells TH 1 cells secrete IFN activate macrophages epithelioid cell and granuloma formation killing of intracellular mycobacteria through production of Nitric oxide and generation of reactive oxygen species
Tuberculosis - Pathogenesis TH-1 response is stimulated by mycobacterial antigens  draining to Lymph Nodes and presented b...
Tuberculosis Pathogenesis
Tuberculosis - Pathogenesis
Tuberculosis Pathogenesis CD8 T cell lysis of infected macrophages with killing of mycobacteria Lysis of the macrophages results in the formation of caseating granulomas mycobacteria being unable to grow in this acidic extracellular contained anaerobic environment are thus
Tuberculosis - Pathogenesis CD8  T cell lysis of infected macrophages with  killing of mycobacteria, Lysis of the macropha...
Notes Defects in any of previous steps of Th 1 response lead to poorly formed granuloma absence of resistance and disease progression Abnormalities in the gene coding for Natural resistance associated macrophage protein 1 can lead to failure of development of an effective immune response and disease progression
Notes     Defects in any of previous steps of Th-1 response lead to poorly formed granuloma, absence of resistance and dis...
Notes Primary cell infected by TB bacilli is Immunity mediated against TB bacilli is mainly mediated by Cell responsible for killing of TB bacilli is Duration needed for developing hypersensitivity reaction on first exposure to TB bacilli is
Notes     Primary cell infected by TB bacilli is            Immunity mediated against TB bacilli is mainly mediated by    ...
Morphology Gross examination Creamy yellow granular cheesy like necrotic material
Morphology Gross examination   Creamy yellow , granular, cheesy-like necrotic material
Primary Tuberculosis Microscopic Morphology Well defined non caseating granulomas are seen here They have rounded outlines Granulomas are composed of transformed macrophages called epithelioid cells along with lymphocytes occasional PMN s plasma cells and fibroblasts The localized small appearance of these granulomas suggests that the immune response is fairly good
Primary Tuberculosis     Microscopic Morphology  Well-defined non-caseating granulomas are seen here. They have rounded ou...
Primary Tuberculosis Microscopic Morphology The site of active involvement shows granulomatous inflammation with or without caseation with multinucleated giant cells that are surrounded by lymphocytes fibroblastic rim
Primary Tuberculosis     Microscopic Morphology     The site of active  involvement shows granulomatous inflammation with ...
Primary Tuberculosis Microscopic Morphology granulomatous Epithelioid inflammation cells minimal central caseation acellular pink areas of necrosis multinucleated giant cells with horse shoe nuclei Langhans cells surrounded by lymphocytes fibroblastic rim
Primary Tuberculosis     Microscopic Morphology     granulomatous     Epithelioid  inflammation   cells    minimal central...
Primary Tuberculosis Microscopic Morphology At high magnification the granuloma demonstrates epithelioid macrophages that are elongated with long pale nuclei and pink cytoplasm The macrophages fuse to form giant cells The typical giant cell for infectious granulomas is called a Langhans giant cell and has the nuclei lined up along one edge of the cell
Primary Tuberculosis     Microscopic Morphology  At high magnification, the granuloma demonstrates epithelioid macrophages...
Primary Tuberculosis Microscopic Morphology This is the acid fast stain of Mycobacterium tuberculosis MTB Note the red rods
Primary Tuberculosis     Microscopic Morphology  This is the acid fast stain of Mycobacterium tuberculosis  MTB . Note the...
Primary Tuberculosis Occurs in previously unexposed therefore unsensitized persons In non immunized children Elderly profoundly immunosuppressed persons may lose their sensitivity to M tuberculosis develop primary tuberculosis Source of infection exogenous Only 5 will develop significant disease
Primary Tuberculosis                         Occurs in previously unexposed   therefore unsensitized persons In non immuni...
Primary Tuberculosis Gross Morphology Typically inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or upper part of the lower lobe usually close to the pleura As sensitization develops 1 1 5 cm area of gray white inflammatory consolidation forms Ghon focus In most cases the center of the focus develops caseous necrosis cheesy like creamy yellow granular necrotic material Tubercle bacilli either free or within macrophage drain into regional lymph node caseating granuloma
Primary Tuberculosis     Gross Morphology    Typically   inhaled bacilli implant in the distal airspaces of the  lower par...
Primary Tuberculosis Gross Morphology Ghon s complex Parenchymal lesion Hilar lymph node involvement
Primary Tuberculosis     Gross Morphology     Ghon   s  complex   Parenchymal lesion   Hilar lymph node involvement
Primary Tuberculosis Fate 1 Fibrosis calcification healing in 95 of cases Only 5 of the newly infected persons are symptomatic Scar may harbor viable bacilli for years and perhaps for life Act as a nidus for reactivation at a later time when host defenses are compromised 2 Progressive primary tuberculosis Occurs in immunosuppressed patients malnourished children elderly The primary focus enlarge and may lead to
Primary Tuberculosis     Fate 1.Fibrosis   calcification    healing    in 95  of cases. Only 5   of the newly infected per...
Primary Tuberculosis Fate Progressive primary tuberculosis A Lower middle lobe consolidation pleural involvement with effusion or empyema hilar lymph node enlargement cavitation is rare B Direct spread Erosion into bronchial tree produces Foci of infection in other parts of the lung Laryngeal tuberculosis from coughed infected sputum Intestinal tuberculosis from swallowing infected sputum
Primary Tuberculosis     Fate    Progressive primary tuberculosis     A. Lower   middle lobe consolidation, pleural involv...
Primary Tuberculosis Fate C Haematogenous spread into blood vessels Will produce Isolated organ tuberculosis The organisms are destroyed in all the organs but persist only in one organ in kidney bone meninges adrenal gland fallopian tubes Systemic generlized miliary tuberculosis When the infective foci seed the pulmonary venous return to the heart dissemination through systemic circulation to different organs especially liver bone marrow spleen adrenals meninges kidneys fallopiantubes and epididymis Morphology Microscopic or small visible 2mm foci of yellow white consolidation scattered throughout the affected organs
Primary Tuberculosis     Fate C. Haematogenous spread into blood vessels      Will produce      Isolated - organ tuberculo...
Tuberculosis Natural History Spectrum Majority
Tuberculosis     Natural History   Spectrum Majority