PATHOLOGY OF CHRONIC PULMONARY INFECTIONS Flashcards
What is chronic pneumonia and what are its general clinical characteristics?
A chronic (infectious) pneumonia often occursin response to organisms that harder to eradicate. Other general clinical characteristics:
x Slow/insidious onset of symptoms (weeks-months)
x Diseasethat persists (months-years)
x Gross and microscopic features are often localized and granulomatous(see image), as the body attempts to wall off the infectious agent
x Control is usually by macrophageingestion or response, in concert with CD4+ T cells
x In the immunocompromised, these diseases may be more severe, prolonged and/or disseminate
Explain the difference between the immunocompetent host and the immunocompromised host in pneumonia?
The immunocompetent host will create well-formed granulomas, while the immunocompromised host mayhavemore macrophages, but they are arranged diffusely, irregularly, and less effectively.
Explain the general features of a M.Tuberculosis infection?
The prototype of a chronic infectious pneumonia, M. tuberculosis causes both pulmonary and systemic disease.
x Classic clinical presentation (which may be seen with many chronic pneumonias): fever, nights sweats, weight loss, cough, hemoptysis
x A positive Mantoux (tuberculin antigen) skin test indicates prior exposure, not active disease
x Individuals with history of BCG vaccine may have a positive PPD test w/o being infected
Explain the pathogenesis of TB?
The pathogenesis of TB follows a sequence of immunologic steps that typify a Type 4 hypersensitivity reaction. After being engulfed by a macrophage…
x M. tuberculosis can block the fusion of the phagosome with a lysosome
x The bacterium can replicate inmacrophages, spread to lymph nodes or elsewhere…
x After a few weeks and by somewhat unknown mechanisms, the immunologic response becomes initiated in full, with IL-12secretionby macrophagecausing Th1 cell differentiation
x Secretion of IFN-γby Th1 cells in turn activates macrophages, enabling them to now effectively form phagolysosomes capable of killing mycobacterium
x With activation, monocyte/macrophages transform into classic epithelioid macrophages that (along with granuloma formation) are the organizing structure that most effectively deals with a high number of organisms
Ghon pathology in TB?
1) The primary Ghon focus is the initial granuloma (left arrow), and the Ghon complexis the Ghon focus + an involved hilar lymph node (down arrow)
Evaluation of potential TB is often done how?
Evaluation of potential TB foci is often carried out clinically, in order that organisms can be cultured, and sensitivity testing performed. In primary infection, the classic features of a caseating granuloma are present. In the image, central caseous necrosis is surrounding by pink, epithelioid macrophages, few have coalesced into giant cells, and partner T lymphsare seen surrounding everything.
Progressive primary TB can appear more?
Progressive primary TB can appear clinically more like an acute bacterial pneumonia, with more progressive symptomatology, such as extensive adenopathy, lobar consolidation (see image), and pleural effusion.
What is latent TB?
3)Latent TB is when the organisms are present but dormant; may be systemic or pulmonary; may reactivate…
what is secondary TB?
4)Secondary TB classically involves reactivation in the upper lobes, but can be quite variable from clinical and pathologic perspectives.
Left image: Miliary TB, present as multiple small white granulomas spread throughout the lung parenchyma; this pattern can occur in any organ in/towhichTB has reactivated or spread.
Right image: Pott disease, which is TB that has spread to the spine. In this image, the TB foci appear as larger, partially cavitary, necroticlesions.
Explain Nocardia asteroides?
Previously thought to be fungal because it grows in aerial extensions (similar to fungal hyphae),
Nocardia is a gram-positive, aerobic bacteria found in soil.
x Indolent with fever, weight loss, and cough –can be mistaken forTB or neoplasm
x Partially suppurative response with liquefaction, but can become fibrotic and walled off; usually doesn’t form granulomas
x More severe/likely in prolonged steroid use, diabetes patients, immunocompromised
Images: Thin, branchingand ‘beaded’ (irregularly staining) filaments of Nocardia, and on modified acid fast stainon the right, where positivity helps separate it from Actinomyces.
Explain Blastomyces dermatitidis ?
A soil-based, dimorphic(grows as a mold/filament in culture/natureand as a yeast in the body) fungus that is common to the central and southeast US.
x pulmonary disease is a mixture of many different localized and constitutional symptoms
x radiographs can show one of many patterns
x can present as isolated cutaneousor disseminated disease patterns Image: cutaneous disease, presenting as erythematous macules and vesicles.
explain the images?
Images: In tissues, the yeasts are 5-15 μm, double contoured cell wall(leftimage arrow), and have broad-based budding(rightimage arrow, silver stain) when they divide.
Explain Histoplasma capsulatum?
Soil-based fungal sporesare infectious and found ubiquitously along the Ohio and Mississippi river valley areas. Clinically, very similar to TB (and Nocardia for that matter):
x Self-limited primary pulmonary involvement with development of coin lesionsradiographically
x Chronic/progressive secondary pulmonary involvement (located in apices) with some constitutional symptoms (fever, night sweats, etc)
x Can spread to extrapulmonary sites
x Wide dissemination with immunosuppression
What happens to histoplasma? Gross appearance? Micro?
Histoplasma is opsonized and then phagocytosed by macrophages, where it can multiply and lyse the macrophage.
x Grossly, fibrotic, often calcified, concentric masses (see image on page 2) will be seen
x Microscopically, a granulomatousreaction with small (3-5 μm), thin-walled yeasts that are intracellular within macrophages(upperimage)
x Silver stain (lower image) can demonstrate oval or pear-shaped yeasts with thin-based budding (arrow)
Explain the images?
Image: a spherule(a yeast form) develops from inhaled arthroconidia (the mold form), and is an intact and walled structure that is fairly large – 20 to 60 microns. In this image, compare the size of the spherulewith the inflammatory cells (8-10 microns) around it. Inside the spherule are numerous endospores, which can spread within the lung or general body when released.
Image: Two smaller spherulesthat are being surrounded by granulomatous inflammation, and ingested within a huge giant cell. Note this image is lower power than the one above it, and the ingested spherules are much largerthan the inflammatory cells near them. Endospores are not visible in this image.
