Pathology of TB & Fungal Infections Flashcards
3 Causes of infectious pneumonia
Inhalation of a infectious agent
1) Pyogenic bacterium
2) Virus
3) TB//Fungus
Manifestation of disease due to inhalation of infectious agent
1) Pyogenic bacterium leads to acute inflammation which produces intra-alveolar pneumonia (lobar or bronchopneumonia)
2) Virus’ cause infection of type I pneumocytes which leads to alveolar injury and then interstitial pneumonia
3) TB/Fungi produce granulomatus inflammation (caseous or necrotizing)
Tuberculosis - definition
A communicable chronic granulomatous disease
Cause of TB
Mycobacterium tuberculosis
Distribution of TB
Usually involves the lungs but may affect any organ in the body
Characteristics of TB -granulomas
-granulomas undergo caseous necrosis (cheesy necrosis) -typically
Species with mycobacterium tuberculosis
M.tuberculosis - human tubercle bacillus
M. bovis - bovine tubercle bacillus (why we pasteurize milk and cheese)
M. africanum - african tubercle bacillus (see in migrants/travellers, edemic North/central Africa, pretty confined to african continent)
M. microti - vole tubercle bacillus (carried by rodents, can transmit to humans usually animal workers)
*big 2 = human TB followed by bovine
Mortality from TB stats
- accounts for 6% of all deaths worlwide
- most common cause of death from a single infectious agent
Number infected with TB worldwide
1.7 million
Infection vs. disease
Infection = seeding of a focus with organisms, which may or may not cause clinically significant tissue damage
Disease = clinically significant tissue damage
Therefore a person may be infected without manifesting the disease
Reservoir of TB
-human with infection or disease
Transmission of TB
- by inhalation of airborne organism in aerosols from infected person
- exposure to aerosolized contaminated secretions
Primary tuberculosis - first 3 weeks - what is happening
A: Cell mediated immunity confers resistance to the organism
- Organisms gobbled up by alveolar macrophages
- Organism overcomes macrophage defence system (bind to receptor, triggers endosomal manipulation = maturation arrest, lack of acid pH) - leads to ineffective phagolysosome formation
- Unchecked baciliary proliferation
- Organism released = bacteremia with seeding of multiple site
* during this time feels reasonably ok, maybe some flu like symptoms
Primary tuberculosis -after first 3 weeks what is happening
B: Cell mediated immunity results in development of tissue hypersensitivity to tb antigens
- body tries to defend itself
- activates immune response ie. alveolar macrophage presents to T cells, which differentiates into Th1 cell to activate macrophages
- macrophages gobble up organisms and release many cytokines, free radicals, chemokines that end causing getting tissue necrosis in surrounding area = caseous necrosis ( a by product body defending itself)
(recruited mnocytes + sensitized t cells surround the caseous necrosis)
Pathologic features of TB
caseating granulomas tissue cavitation (formation of cavities- when necrotic tissue breaks down)
What causes caseating granulomas and tissue cavitation
Are the result of destructive tissue hypersensitivity that constitutes host immune responses
Typical distribution of primary TB
- inhaled bacilli implant in distal air spaces of lower part of upper lobe or the upper part of lower lobe
- usually close to the pleura (in the periphery?)
Consequences of unchecked bacillary proliferation (i.e. in patients with HIV - low CD4+ count)
-will in time proliferate in every cell in body and ultimately die
Ghon focus
- a 1-1.5 cm area of grey-white inflammatory consolidation
- produced as sensitization to TB develops
- center of this focus will undergo caseous necross
Lymph nodes during TB
-bacilli either free or within macrophages drain to regional lymph nodes (i.e. hilar lymph nodes) which will then caseate
Ghon complex
The combintion of parenchyma lesion (ghon focus) and nodal involvement
Histology of caseating granuloma -layers
- central necrosis
- surrounded by epitheliod histocytes alot of thse merge to form multinucleated histiocytes
- surrounded by lymphocytes
Importance of looking for ghon focus on chest x-ray
1) if calcified/fibrotic - old TB
2) If growing - worry about reactivation of TB or lung cancer development
Identifying mycobacteria histologically
- stain center of caseating granuloma (central necrosis region most likely to find organisms)
- stain with Ziehl -Neelsen stain ->purple = mycobacteria
Dissemination of primary TB
-during 1st few weeks get lymphatic and hematogenous dissemination to other parts of body
Outcome of primary TB for the majority of people
- in 95% of cases cell mediated immunity controls the infection
- seeds to other organs but no lesions develop
- ghon complex undergoes progressive fibrosis (producing radiologically detectable calcification)
Foci of scarring - importance
May harbour viable bacilli for years and perhaps for life
-will be the site for reactivation at a later time when host defences are compromised
Why might host defences be compromised leading to reactivation of TB
- old age
- malnutrition
- HIV
- cancer/chemotherapy.. etc
Progressive primary TB (+pathogenesis/cause)
uncommonly the course of the disease will continue without interruption into a progressive primary TB
- typically occurs in immuno-compromised states (malnourished, elderly, AIDS, certain racial groups such as Inuit)
- can’t mount CD4+ response that would contain primary fcus
Consequence of primary progressive tuberculosis
- May result in miliary TB
- May result in tuberculous meningitis
Miliary tuberculosis
- microgranulomas (millet seeds or micro nodules) in the lung, and spleen
- see thousands of nodules in the lung (if see this either TB, metastatic cancer or sarcoidosis)
Secondary TB
- aka reactivation tuberculosis/cavitary TB
- the pattern of disease that arises in a previously sensitized host
Causes of secondary TB
A) reactivation of dormant primary lesions
-occurs usually many decades after initial infection particularly when host resistance is weakened
B) may also result from exogenous re-infection (especially in areas where TB is endemic)
Localization of secondary pulmonary TB
-localized to the apex of one or both upper lobes
Reason why secondary TB localizes here
Relates to higher oxygen tension in apices (hypothesis)
Characteristics of secondary TB
- intial lesion usually < 2 cm in diamter, within 1-2 cm of apical pleura
- variable amounts of central caseation and peripheral fibrosis
- cavitation occurs readily –> results in dissemination along the airways
- because body already sensitized - launches major response and get the collateral damage
Source of infectivity in secondary TB
- cavitation releases TB into airway
- get erosion into an airway
- person now raises sputum containing bacilli
Outcome of favorable cases of secondary TB
- undergo progressive fibrous encapsulation
- leaving only a fibro-calcific scar
- happens either spontaneously or after therapy
Complications of secondary TB
1) progressive pulmonary tuberculosis
2) erosion into bronchi with cavitation
3) blood vessel erosion resulting in hemoptysis
4) miliary pulmonary disease
5) pleural effusion/tuberculous empyema (infectious process going on in the pleura)
6) endobronchial, endotracheal, laryngeal TB
7) Systemic miliary tb
8) Isolated-organ tuberculosis (including tuberculous meningitis
9) lymphadenopathy (usually cervical region= scrofula)
10) Death
Nontuberculous mycobacterial disease in the immunocompetent host -strains that can cause this disease
- Mycobacterium avium complex
- Mycobacterium kanasasii
- Mycobacterium abcessus
Clinical presentation of nontuberculous mycobacterial disease in immunocompetent host
-can present as upper lobe cavitary disease (mimicking tb) especially in those with longstanding history of smoking or alcoholism
Risk factor for nontuberculous mycobacterial disease in immunocompetent host
- Chronic obstructive pulmonary disease
- Cystic fibrosis
- Pneumoconioses
Nontuberculous mycobacterial disease in immunocompromised host (primarily HIV)- clinical presentation
Infection by Mycobacterium avium complex
1) disseminated disease with systemic symptoms (fever, night sweats, weight loss)
2) Hepatosplenomegaly and lymphadenopathy
3) GI symptoms (diarrhea and malabsorption)
4) Pulmonary symptoms often indistiguishable from TB in aids patients
When does disseminated mycobacterium avium complex infection tend to occur in AIDS patients
tends to occur late in the disease when the CD4+ count is less than 100 cells/mm3
Granulomas in tissue examination of AIDS patient?
Not usually present because body never mounted a response vs. mycobacterium avium complex (MAC)
Histological findings in tissue examination of AIDS patient with MAC
-proliferation of foamy macrophages stuffed with atypical mycobacteria
Multidrug resistance tuberculosis (MDR-TB)-definition
-resistance of mycobacteria to two or more of the primary drugs used for treatment
In which patients is MDR-TB a particular concern
In patients with HIV infection
Prognosis of TB
-generally favorable if infection localized to lungs Worsens significantly if: a) aged b) debilitated c) immunocompromised d) MDR-TB
Macroscopic appearance of TB
Caseation necrosis
Microscopic appearance of TB
necrotizing granulomatous inflammation
Pathological differential diagnosis of TB
-fungal infection (can also cause necrotizing granulomatous inflammation)
Fungal infections + how they manifests in the immunocompetant host + how th
1) Blastomyces dermatidis
2) Histoplasma capsulatum
3) Coccidioides immitis
4) Cryptococcus neoformans
5) Cryptococcus gattii
Manifest as fungal spores in tissue
Manifestation of fungal infections in immunocompromised host
-fungal hyphae in tissue
Pathology of fungal infections in the immunocompetent host - findings
1) Pathological and clinical/radiological similar to TB
2) granulomatous inflammation with necrosis
3) acute (primary) pulmonary infection
4) chronic (including cavitary) pulmonary disease
5) disseminated miliary disease
6) solitary pulmonary nodule resembling bronchogenic carcinoma radiologically
7) peri-hilar mass/lymphadenopathy resembling bronchogenic carcinoma radiologically
How to differentiate fungal infection in immunocompetent host from TB
-identification of fungal organism in tissue /culture
Differential diagnosis for fungal nodules
- TB
- CANCER (big differential diagnosis)
Histological findings cryptococcus
- H&E staining: Giant cells with organism within in
- Silver staining: Pinpoint budding
- Mucicarmine staining: mucicarmine positive (stains mucinous wall)
Histological findings coccidiodes
H&E stain - coccidioidal spherule containing endospores
Silver stain - endospores (take up silver stain)
-Mucicarmine staining: negative
Histological findings blastomyces
-Broad based budding (seen with H&E stain and Periodic acid schiff staining)
Histological finding Histoplasma
-Silver stain (not visible on H&E stain) -can see the spores here
Fungal infections in the immunocompromised host -sources
1) Aspergillus
2) Candida
3) Mucor
Consequences of fungal infections in the immunocompromised host
1) Necrotizing pneumonia
2) Propensity for blood vessel invasion (angioinvasion) = vessels stuffed with fungi and leading to conseqeunt tissue infarction and dissemination (especially to the brain leading to brain abscess)
Sarcoidosis -cause
Unknown
Sarcoidosis characteristic
- non-caseating
- non-necotizing granuloma
Differential diagnosis sarcoidosis
- mycobacterial and fungal infections sometimes produce non-caseating/non-necrotizing granulomas
- sarcoidosis is the major differential diagnosis of infectious granulomatous inflammation
Diagnosing sarcoidosis
-diagnosis of exclusion
