PULMONARY TUBERCULOSIS

Dr. Thin Thin Win @ Safiya Yunus Department of Pathology, PPSP

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Attention to all students

For your cooperation in H1N1 control If you have fever. Please leave the class/ lecture hall get yourselves quarantined in the hostel or at home

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Tuberculosis
Tuberculosis (TB) is an infectious disease caused by bacteria Genus Mycobacterium (most common species - Mycobacterium tuberculosis) Commonly affects the lungs also can involve almost any organ of the body
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Causal organisms of Tuberculosis

 Acid fast bacilli (AFB) waxy cell wall c/o

mycolic acid  Genus - Mycobacterium

 species
Mycobacterium tuberculosis Mycobacterium bovis Mycobacterium avium (avium, hominis, paratuberculosis) Mycobacterium intracellulare
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Pulmonary TB
Mycobacterium tuberculosis - typical tuberculosis Mycobacterium avium intracellulare complex (MAC) - atypical tuberculosis

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Portal of entry
1. Inhalation of infected aerosols/droplets 2. Ingestion of infected sputum or contaminated milk (GI Tuberculosis) 3. Direct penetration through abraded skin (skin Tuberculosis)

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2 types of pulmonary TB
Primary TB form of disease that develops in a previously unexposed & unsensitized person Source of organism - exogenous

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2 types of pulmonary TB
Secondary TB pattern of disease that arise in a previously sensitized host reactivation of dormant primary lesions when host resistance is weakened Source of infection endogenous or exogenous
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Pathogenesis
1. Virulence of organism 2. Introduction of a delayed hypersensitivity reaction (type IV) 3. Development of cell mediated immunity & tissue destruction
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Virulence of organism Ability to escape killing by macrophages after phagocytosis Glycolipid in bacterial cell wall lipoarabinomannan(LAM) Cord factor, Heat shock protein Sulfatides prevent fusion of phagosomes (containing organism) to lysosomes
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Within 3 wk: Lipoaraninomannan (glycolipid in bacterial cell wall) resist endocytosis by macrophages Bacilli enter macrophages (primary cells to be infected) & proliferate (by blocking fusion of phagosome & lysosome) Bacteremia, but most pt: are asymptomatic or mild flu-like illness
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Events occurring in the first 3 wks after exposure

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After 3 wk: Macrophages (primary cells infected by organism) present bacterial Ag to T 1cell with class II MHC IL-12 produced by Ag presenting cells differentiate T 1cell T 1cell IFN IFN- activate macrophages with acid environment Activated macrophages TNF recruits monocytes epitheloid granuloma
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Events occurring after 3 wks. Development of resistance to organism is accompanied by (+)ve tuberculin test
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Sequence of events in primary tuberculosis

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Infection by Mycobacterium tuberculosis Bacilli enter into macrophages Antigenic peptide presented to CD4 Tcell by macrophages via interaction b/t Class II MHC & CD4Tcell Cytokines production (IFN- & TNF)

Delayed hypersensitivity Rx

Cell mediated Immunity

activated macrophage bactericidal activity

Granuloma

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Primary pulmonary TB
Sites of P tuberculosis (1) lung P focus + regional lymph node Ghon complex (2) SI - P focus + mesenteric lymph node Tabes mesentrica (3) oropharynx - P focus + regional LN collar stud cold abscess (4) skin - P focus + regional lymph node lupus vulgaris drttw (2009) 17

Morphology of P pulmonary TB At lower part of upper lobe or upper part of lower lobe, close to pleura 1- 1.5 cm area of gray white inflammatory consolidation Ghon focus Centre of focus caseous necrosis Combination of peripheral lung lesion & regional lymph node enlargement Ghon complex
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Ghon complex:

subpleural Ghon focus & hilar lymph node granuloma

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Histology Characteristic granulomatous inflammatory reaction with both caseating and non-caseating tubercles Granuloma/Tubercles enclosed within fibroblastic rim, punctuated by epitheloid cells, lymphocytes, plasma cells, multinucleated giant cells with Langhans giant cell No granuloma in immunocompromised pt:
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Granuloma

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Multiple caseating granuloma

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Langhans giant cell

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Caseation in granuloma

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Red color rod shaped acid fast bacilli in Ziehl-Neelsen stain

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Outcome of PTB Most cases does not progress Ghon focus shrinkage, fibrosis, dystrophic calcification, fibrous scarring & puckering of adjacent pleura Tracheobronchial node replaced by fibrocalcified scarring Infecting organism not totally eradicated, may remain viable & can be reactivated If progress erosion of bronchial tree, miliary TB drttw (2009) 26

Secondary TB
Synonyms - post primary TB - reinfected TB - reactivated TB Phase of TB infection that arise in a previously sensitized individual Source of infection endogenous (reactivation of asymptomatic previous PTB due to reduced host resistance)
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Morphology of STB Gross Apex of upper lobes of one or both lungs ( O2 tension promotes growth of bacteria) Initial lesion small focus of consolidation <2cm in diameter within 1-2 cm of apical pleura Firm, gray-white to yellow with variable amount of central caseation yellowish cheesy appearance
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Morphology of STB Histology Characteristic coalescent tubercles (granulomas) with central caseation Histology of granuloma same as in primary TB

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Pulmonary Tuberculosis
The pathology is almost confined to the upper lobe, particularly apex with cheesy caseous necrosis together and cavity formation.

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Pulmonary Tuberculosis
Extensive caseation and the granulomas involve a larger bronchus, necrotic center to drain out and leave behind a cavity. Cavitation is typical for large granulomas with tuberculosis. Cavitation is more common in the upper lobes.
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Pulmonary Tuberculosis
The granulomas have areas of caseous necrosis. This is very extensive granulomatous disease. This pattern of multiple caseating granulomas primarily in the upper lobes is most characteristic of secondary (reactivation) tuberculosis.
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Old, healed calcified tuberculous lesion in the lung

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Outcome of apical pulmonary lesion

1. Apical fibrocalcific arrested TB with adequate treatment 2. Erosion into bronchus cavitation lined by caseous material Erosion into blood vessels hemoptysis

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Outcome of apical pulmonary lesion

3. Miliary tuberculosis - if inadequate treatment - Infection may spread by airways , lymphatic channels or vascular system - Through lymphatic Rt heart lung small foci of consolidation scattered through lung parenchyma like foci of millet seeds (miliary pulmonary TB)
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Miliary TB, lung: Cut surface shows multiple small foci of granuloma resemble millet seeds (sago seed)

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Miliary Tuberculosis

Miliary tuberculosis of the spleen. The cut surface shows numerous gray-white granuloma.
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Outcome of apical pulmonary lesion

4. Systemic miliary TB - infected foci from lung systemic arterial circulation - liver, BM, spleen, adrenals, meninges, kidneys, fallopian tubes, epididymis 5. Pulmonary lesion erode to pleura - pleural effusion, tuberculous empyema - obliterative fibrous pleuritis
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Outcome of apical pulmonary lesion

6. Pulmonary lesion erode bronchi - endobronchial, endotracheal & laryngeal tuberculosis 7. Infected sputum is swallowed organism trapped in mucosal lymphoid tissue & ulceration of mucosa particularly in ileum intestinal tuberculosis

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Outcome of apical pulmonary lesion

8. Isolated organ TB by haematogenous spread (meninges, kidneys, adrenals, bones, fallopian tubes ) 9. Tuberculous lymphadenitis - most frequent form of extra-pulmonary TB - usually in cervical region ( scrofula ) 10. Systemic secondary amyloidosis 11. Scar cancer
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Mycobacterium Avium-Intracellulare Complex MAC - Mycobacterium avium - Mycobacterium intracellulare Uncommon except in AIDS & immunocompromised patients

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Morphology Hallmark - abundant AFB within macrophages Granuloma, lymphocytes & tissue destruction are rare Widely disseminated throughout mononuclear cellular system, causing enlargement of LN, liver & spleen

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Mycobacterium avium intracellulare in macrophages/ histiocytes of lymph node

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Diagnosis of Tuberculosis
History Physical findings Radiological findings Pathological findings Identification of AFB in smear Culture of tubercle bacilli Identification of M.tuberculosis DNA by PCR
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