Pathology of Tuberculosis and Fungal Infection Flashcards
Tuberculosis I -characteristics
- communicable
- chronic
- granulomatous (typically granulomas undergo caseous necrosis)
- usually involves the lung but may affect any organ in the body
Cause of TB I
Mycobacterium tuberculosis
Tuberculosis IV reservoir
-in humans with infection/disease
Tuberculosis IV transmission
- inhalation of airborne organisms in aerosols from infected person
- exposure to aerosolized contaminated secretions
Primary pulmonary TB -mechanism developement first 3 weeks
-mannose-capped glycolipid on mycobacterium binds to macrophage mannose receptor on airway macrophage
-mycobacterium enters the macrophage
-inside mycobacterium causes endosomal manipulation :
a) maturation arrest
b) lack of acid pH
c) ineffective phagolysosome formation
so can survive in the cell and get unchecked bacillary proliferation
-bacteremia with seeding to multiple sites
Primary pulmonary TB -mechanism development past 3 weeks
1) Infected alveolar macrophage activates naive T-cell
(presenting MTB antigen on class II MHC to the T-cell receptor + IL-12)
2) naive T cell differentiates to TH1
3) TH1 releases IFN-y whch activates macrophages
4) Activated macrophage secretes TNF. chemokines, nitric oxide and free radicals
5) TNF, chemokines lead to monocyte recruitment
4) Causes caseous necrosis, and sensitized T cell (epithelioid granulom)
Why does TB survive in the body
Cell mediated immunity confers resistance to the organism
Consequence of TB survival in the body
-cell mediated immunity results in developmet of tissue hypersensitivity to tubercular antignes
Cause of pathological features of TB i.e. caseating granulomas and tissue cavitation
- result of destructive tissue hypersensitivity that constitutes the host immune response
- i.e. the immune response comes at the cost of hypersensitivity and accompanynig tissue destruction
Primary TB I -in who it develops
-develops in previously unexposed person
Source of organism in Primary TB 1
- exogenous source
- typically inhaled bacilli implant in distal air spaces of lower part of upper lobe or the upper part of the lower lobe
Location of bacilli in primary TB 1
-inhaled bacilli implant in distal air spaces of lower part of upper lobe or upper part of lower lobe (usually close to the pleura)
Ghon focus
- a 1- 1.5 cm area of grey-white inflammatory consolidation
- happens when sensitization develops in primary TB II
Ghon complex
-combination of parenchymal lesion (ghon focus) and nodal involvement (as TB drain to regional lymph nodes which also often caseates)
Primary TB III characteristics
-during first few weeks also get lymphatic and hematogenous dissemination to other parts of the body
Ghon complex in primary TB III
- undergoes progressive fibrosis
- often followed by radiologically detectable calcification
Primary TB IV -characteristics
- foci of scarring may harbour viable bacilli for years –> potential for reactivation at a later time when host defences compromised
- uncommonly the disease may develop into so-called progressive TB
When progressive primary TB occurs
- in immunocomprommised states:
a) malnourishment
b) elderly age group
c) AIDS
d) certain racial group ie Inuit
Why progressive primary TB occurs
-immunosuppression leads to inability to mount CD4+ T-cell mediated immunologic reacion that would contain the primary focus
Consequences of progressive primary TB
- miliary tuberculosis
- tuberculous meningitis
Miliary tuberculosis
X
Tuberculous meningitis
X
Secondary tuberculosis I -what is it
-the pattern of disease that arises in a previously sensitized host
Causes of secondary tuberculosis I
- Arises from reactivation of dormant primary lesions
- usually when host resistance is weakened but also from exogenous re-infection
- usually many decades after initial infection
Location of secondary tuberculosis II
-classically localized to the apex of one or both upper lobes
Reason for secondary TB II
-may related to high oxygen tension in the apices
Consequences of secondary TB II
- cavitation occurs readily in the secondary form
- results in dissemination along the aiways
Source of infectivity in secondary TB II
-erosion into an airway –> person raising sputum containing bacilli
Secondary TB III characteristics
- initial lesion less than 2 cm in diameter (within 1-2 cm of apical pleura)
- variable amount of central caseation and peripheral fibrosis
Secondary TB IV characteristics
- localized apical secondary pulmonary TB
- may heal with fibrosis spontaneously or after therapy or disease may progress along several different pathways
Complications of secondary pulmonary TB 1
- progressive pulmonary tb
- erosion into bronchi with cavitation
- blood vessel erosion results in hemoptysis
- miliary pulmonary disease
- pleural efffusion/tb empyema
- endobronchial, endotracheal laryngeal TB
Complications of secondary TB II
- systemic miliary TB
- isolated-organ tb including tb meningitis
- lymphadenopathy, usually cervical region (scrofula)
- death
Strains causing nontuberculous mycobacterial disease in immunocompetent host
Strains
- mycobacterium avium complex
- mycobacterium kanasasii
- mycobacterium abcessus
Presentation of nontuberculous mycobacterial disease in immunocompetent host
-upper lobe cavitary disease (mimicks TB)
Risk factors of nontuberculous mycobacterial disease -immunocompetent host
- chronic obstructive pulmonary disease
- cystic fibrosis
- pneumoconioses
Nontuberculous mycobacterial disease-immunocompromised host (primarily HIV positive disease) -I presentation
1) Mycobacterium avium complex - presents as disseminated disease with systemic symptoms (fever, night sweats, weight loss)
- hepatosplenomegaly and lymphadenopathy (involvement of mononuclear phagocyte system are common)
- gastrointestinal symptoms such as diarrhea and malabsorption also common
- pulmonary involvement often indistinguishable from tuberculosis in AIDS patients
Nontuberculous mycobacterial disease -immunocompromised host (primarily HIV positive disease)-II
- disseminated mycobacterium avium complex infection in AIDS patients tends to occur late in the disease when CD4 count is less than 100 cells/mm3
- tissue examination usually dose not reveal grnulomas
- proliferation of foamy macrophages “stuffed” with atypical mycobacteria
Multidrug resistance tuberculosis (MDR-TB)
-MDR-TB is defined as resistance of mycobacteria to two or more of the primary drugs used for treatment
Prognosis of TB
- favorable if infection localized to lungs
- worsens significantly in
a) aged
b) debilitated
c) immunocompromised
d) MDR-TB
