The Lung part 5 Flashcards
1
Q
Development of pneumoconiosis depends on what 3 things?
A
1) amount of dust retained in lung
2) size, shape and bouncy of particles
3) particle solubility and physiochemical reactivity
4) possible additional effects of other irritants (smoke, et)
* these particles stimulate resident innate immune cells in lung
2
Q
General principles that apply to pneumoconioses
A
- Amount of dust retained in lungs determined by dust concentration in air, exposure duration, effectiveness of clearance mechanisms
- Most dangerous are particles of 1-5um–settle in terminal airways and air sacs
- solubility and cytotoxicity of particles (influenced by size) modify pulmonary response–small particles of high solubility cause rapid onset lung damage while larger particles resist dissolution and persist in lung for years leading to fibrosing collagenous pneumoconiosis like silicosis
3
Q
General principles that apply to pneumoconiosis counted
A
- Other particles may be taken up by epithelial cells or may cross epithelial cell lining and interact directly with fibroblasts and interstitial macrophages; some reach lymphatics by direct drainage or within migrating macrophages initiating immune response to components of particulates or to self-proteins modified by particles or both
- certain types of particles activate inflammasome when phagocytosed by macrophages; these innate and adaptive immune responses amplify intensity and duration of local reaction
- Tobacco smoking worsens effects of all inhaled mineral dusts but esp those caused by asbestos; effects of inhaled particles not confined to lung alone since solutes from particles can enter blood and lung inflammation invokes systemic responses
4
Q
occupational respiratory diseases common or rare?
A
-rare, implying genetic predisposition to development
5
Q
Coal workers pneumoconiosis
A
- lung disease caused by inhalation of coal particles and other admixed forms of dust
- reduced incidence bc reduced dust in coal mines
- varies from asymptomatic antracosis to simple coal workers pneumoconiosis with little pulmonary dysfunction to complicated CWP or progressive massive fibrosis where lung function compromised
- silica in coal dust favors progressive disease
- carbon coal dust major culprit–more=worse/complex
- may develop emphysema and chronic bronchitis independent of smoking
6
Q
Anthracosis morphology
A
- least harmful coal miners pulmonary lesion; also seen in urban dwellers and tobacco smokers
- inhaled carbon pigment is engulfed by alveolar or interstitial macrophages which then accumulate in connective tissue along the lymphatics or in organized lymphoid tissue along bronchi or in lung hilus
7
Q
Simple coal workers pneumoconiosis morphology
A
- COAL MACULES (1-2mm) and larger COAL NODULES
- coal macule have carbon-laden macrophages; nodules have collagen
- Upper lobes and upper zones of lower lobes involved!
- near resp bronchioles where dust initially accumulates
- coarse dilation of near alveoli occur sometimes leading to centrilobular emphysema
8
Q
Complicated coal workers’ pneumoconiosis morphology
A
- progressive massive fibrosis
- occurs on top of simple disease, takes years to develop
- MULTIPLE, intensely blackened scars 1cm-10cm large
- have dense collagen and pigment
- center of lesion is necrotic due to local ischemia
9
Q
Clinical coarse of CWP
A
- benign, little impact on lung fix even in complicated CWP
- in RARE cases, progressive massive fibrosis occurs leading to increasing pulm dysfnx, pulm HTN, cor pulm
- once progressive fibrosis develops, it can worsen even if exposure to dust is prevented
- unlike silicosis, no evidence linked to risk for TB
- no evidence that CWP w/o smoking leads to cancer
- BUT indoor use of “smoky coal” (bituminous) for cooking and heating associated with increased risk of lung cancer death for both men and women
10
Q
Silicosis
A
- common lung disease caused by inhalation of pro inflammatory crystalline silicon dioxide (silica) that presents after decades of exposure; slowly progressing, nodular, fibrosing pneumoconiosis
- most prevalent chronic occupational disease worldwide
- African Americans at higher risk than whites!
- risk occupations: repair, rehab or demolition of concrete structures like buildings and roads
- less commonly in sandblasters (stressed denim), stone carvers, and jewelers using chalk molds
- sometimes, heavy exposure over months/years result in acute silicosis–see accumulation of lipoproteinaceous material in alveoli (identical to alveolar proteinosis)
11
Q
Pathogenesis of silicosis
A
- silica both in crystalline/amorphous forms but crystalline forms (quartz, cristobalite, tridymite) more fibrogenic
- quarz most comply implicated
- once inhaled, particles phagocytosed by macrophages and phagocytized silica crystals activate inflammasome releasing IL-1 and IL-18
- benign response in coal and hematite miners bc coating silica w/other minerals esp clay makes silica less toxic
- Amorphous form less active but heavy exposure can still cause lesions
12
Q
Silicosis morphology
A
- early: tiny, barely palpable, discrete pale to blackened nodules in hilar lymph nodes and UPPER zones of lungs
- As progresses, nodules become hard, collagenous scars
- some nodules undergo central softening and cavitation due to superimposed TB or ischemia
- Fibrotic lesions may occur in hilar lymph nodes/pleura
- Thin sheets of calcification occur in lymph nodes and seen radiographically as EGGSHELL calcification (calcium surrounding zone lacking calcification)
- If disease continues progressing, expansion and coalescence of lesions produces progressive massive fibrosis
- Histo exam: hallmark lesion w/central area of whorled collagen fibers with more peripheral zone of dust-laden macrophages
- Exam of nodules by polarized microscopy shows birefringent silicate particles (silica weakly bifringent)
13
Q
Clinical course of silicosis
A
- Chest X-ray shows fine modularity in upper zones of lung
- Pulm fnx either normal or only slightly affected early on and NO SOB until massive fibrosis occurs
- can worsen even if pt no longer exposed
- slow to kill but pulm dysfnx can severely limit activity
- increases susceptibility to TB! bc crystalline silica inhibits ability of pulm macrophages to kill phagocytized bacteria
- slow onset (10-30 yrs more common) or rapid (wks/months after intense exposure–rare)
- Double the risk of developing lung cancer!!
14
Q
Asbestos
A
-family of pro inflammatory crystalline hydrated silicates associated with pulmonary fibrosis, carcinoma, mesothelioma, and other cancers
15
Q
Asbestos-related diseases include
A
- Localized fibrous plaques or rarely diffuse pleural fibrosis
- Pleural effusions, recurrent
- Parenchymal interstitial fibrosis (asbestosis)
- Lung carcinoma
- Mesotheliomas
- Laryngeal, ovarian and other extra pulmonary neoplasms including colon carcinomas; increased risk for systemic autoimmune diseases and cardiovascular disease proposed
- increasing incidence of asbestos related cancers
16
Q
Pathogenesis of asbestos related diseases depends on
A
-disease causing ability depend on conc, size, shape and solubility of different forms of asbestos
17
Q
Asbestos forms
A
- 2 forms: serpentine chrysotile and amphibole
- serpentine is most common form used in industry
- Amphiboles, less prevalent but more pathogenic than chrysotile esp in causing mesothelioma
- Amphiboles more pathogenic bc of aerodynamic properties and solubility; chrysotile more flexible, curled so get stuck in upper resp passage and removed by mucociliary elevator and are also more soluble so eventually gets out from tissues; in contrast, amphiboles are straight, stiff and align in the airstream and delivered deeper into lungs where they penetrate epithelial cells and reach interstitium
- Both amphiboles and serpentine fibrogenic and higher doses=higher incidence of asbestos related diseases
18
Q
Asbestos is unique from other inorganic dusts in that it can also
A
- act as a tumor initiator and promoter
- oncogenic effects mediated by reactive free radicals from asbestos fibers which like to localize to DISTAL lung, close to mesothelial layers
- Toxic chemicals adsorbed onto asbestos fibers also likely contributes to oncogenicity of fibers like tobacco smoke
- smoking also enhances asbestos effect by interfering with mucociliary clearance of fibers
- asbestos and smoking=55x higher risk for lung cancer
19
Q
Asbestos similarity to silica crystals in terms of pathogenicity
A
- Like silica crystals, once phagocytized by macrophages, asbestos fibers activate inflammasome and releases pro inflammatory factors and fibrogenic mediators
- initial injury occurs at bifurcation of small airways and ducts where asbestos fibers land, penetrate and are directly toxic to pulm parenchymal cells
- Alveolar and interstitial macrophages try to ingest and clear fibers and persistently release mediators (ROS, proteases, cytokines, GFs) leading to generalized interstitial pulmonary inflammation and interstitial fibrosis
20
Q
Asbestos morphology
A
- diffuse pulmonary interstitial fibrosis w/ multiple ASBESTOS BODIES–golden down, fusiform, beaded rods with translucent center and consist of asbestos fibers coated with iron-containing proteinaceous material!!
- > arise when macrophages phagocytose ferritin; other inorganic particulates may become coated with similar iron-protein complexes–called ferruginous bodies
- Rare single asbestos bodies found in normal lungs
21
Q
Asbestosis morphology progression of disease
A
- begins as fibrosis around resp bronchioles and alveolar ducts and extends to alveolar sacs and alveoli
- fibrosis distors architecture, creating large airspaces with thick fibrous walls w/region becoming honeycombed
- pattern similar to usual interstitial fibrosis w/fibroblastic foci and varying degrees of fibrosis, only difference being presence of numerous asbestos bodies
- Unlike CWP and silicosis, asbestosis begins in LOWER lobes and SUBpleurally; middle and upper lobes affected as fibrosis progresses; scarring may trap and narrow pulm arteries and arterioles causing pulm HTN/cor pulmonale
22
Q
Pleural plaques
A
- Most common manifestation of asbestos exposure
- well circumscribed plaques of dense collagen, is calcified
- usually on anterior and posterolateral parietal pleura and over domes of diaphragm
- size/ number of pleural plaques=no correlation to level of exposure to asbestos or to time since exposure
- do NOT contain asbestos bodies but RARELY ever occurs in patients w/no history of asbestos exposure
- Rarely, asbestos induces pleural effusions which are serous but can be bloody
- Also rarely, diffuse visceral pleural fibrosis occur and in advanced cases, bind lung to thoracic wall
