pneumoconiosis

Report
Pneumoconiosis
Definition
• Non neoplastic lung reaction to inhalation
of mineral dusts encountered in the
workplace.
• Also includes diseases induced by organic,
inorganic particulates and chemical fumes
and vapors.
• Important to diagnose as they are
“occupational lung diseases.”e.g. silica, coal,
asbestos
•
Some dusts e.g. tin, iron are innocuous
Nomenclature
• According to the causative agent –
silicosis
• Occupation eg knife grinders
lung=silicosis
Normal protective
mechanisms
• Mucociliary apparatus >10 μm diameter,
deposit in bronchi & bronchioles and
removed in the mucociliary escalator.
• Intra-alveolar macrophagesphagocytosis of particles &
expectorated. Some go through
interstitium into lymphatics.
• Very Small particles behave like gas &
•
exhaled
Normal protective
mechanisms
• Nose & trachea traps all particles >10 μm
& 50% of 3μm
• Mucociliary blanket 2-10 μm removed in
the mucociliary escalator.
• Alveolar macrophages <2 μm removed
• Very small particles are not
phagocytosed,but exhaled.
Factors affecting
fibrogenic potential
• Amount of dust retained in the lung
(concentration, duration, clearence
mechanisms)
• Size, shape and bouyancy of
particles(aerodynamic diameter) (1-5μ size
dangerous sized particles reach the
periphery : bronchioles & alveoli)
• Additional effects of other irritants
(smoking)
•
Solubility & physiochemical
•
reactivity
Factors affecting (cont…)
• Solubility & cytotoxicity of particles
• Small particles dissolve in pulmonary fluids→
acute toxicity
• Larger,non soluble persist in lung parenchyma
• Some dusts directly penetrate the epithelial
cells into the interstitium.
• Physiochemical reactivity
• Direct injury to tissue (free radicals )e.g.
Quartz
•
Fibrosing pneumoconiosis (eg silicosis)
Pathogenesis of fibrosis
• Ingested dusts trigger macrophages to
release chemical mediators that trigger
fibrosis (TNF, IL 1,PDGF).
• Persistent release of factors causes
fibrosis
• Migrating macrophages to lymphatics
trigger immune reaction
• Fibrosis (nodular-silica, interstitial –
•
asbestos ??)
Pathogenesis
• Inhalation
• Escape removal by defence apparatus
• Particles penetrate epithelium → direct
injury
• Fibrosis
• Engulfment by alveolar & interstitial
macrophages → lymphatics → lymph
node (modify immune response )
Coal workers pneumoconiosis
(CWP)
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•
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•
Associated with coal mining industry
Carbon + silica (anthracosilicosis)
Classification
Asymptomatic anthracosis
(anthracite –coal)
• Simple CWP- no dysfunction
• Complicated CWP- (progressive
massive fibrosis PMF)
Anthracosis (urban
dwellers)
morphology
• Gross Streaks of anthracotic
pigment in lymphatics and draining
hilar lymph nodes
• Microscopy
• Carbon pigment in alveolar and
interstitial macrophages,in
connective tissue and lymphatics
•
and lung hilus.
Simple CWP
Gross :Coal macules (1-2mm) & Coal
nodules >upper lobes and upper zones
of lower lobes
Microscopy: Carbon laden macrophages
& delicate collagen fibres. Adjacent
to respiratory bronchioles initially
(where dust settles), later interstium
& alveoli.
Dilatation of respiratory
bronchioles –focal dust emphysema
Complicated CWP
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•
Gross
Multiple.,>2 cm ,v dark scars
Microscopy:
Dense collagen and carbon pigment.
Central necrosis (+/-)
Clinical course
• Usually asymptomatic with little
decrease of lung function
• PMF pulmonary dysfunction (restrictive)
• Pulmonary hypertension, cor pulmonale
• Progressive even if further exposure to
dust is prevented
• ↑ chronic bronchitis and emphysema
•
No association with TB or carcinoma
Caplans syndrome
• 1st described in coal workers, may be
seen in other pneumoconiosis
• ?? Immunopathologic mechanism
• Rheumatoid arthritis (RA) + Rheumatoid
nodules (Caplan nodules) in the lung
• Rheumatoid arthritis + pneumoconioses
• Caplans nodule = necrosis surrounded by
fibroblasts,monocytes and collagen
• s/s RA > lung symptoms
Silicosis
• Silicosis-nodular fibrosing disease after
20-40 yrs exposure to silica
• Sand blasters,mine workers,stone
cutting,polishing of metals,ceramic
manufacturing etc.
• (Acute silicosis following massive
exposure –alveolar lipoproteinosis like.
Rapidly progressive disease. )
Pathogenesis
• Fibrogenic activity depends on physical form,
association with other minerals.
• Crystalline silica (quartz) more toxic.
• (Amorphous forms talc, mica less toxic)
• Size 0.2-2μm more dangerous
• Silica particles ingested by alveolar
macrophages, kill them and release fibrogenic
factors. Released silica ingested again.
• Recruitment of lymphocytes and macrophages
•
Fibrotic silicotic nodule
Gross Morphology
• Discrete pale to black nodules <1cm
dia.
• Upper zone of lungs
• Hard collagenous scars-central
softening
• Fibrosis in hilar lymph nodes and
pleura
• Enlarged fibrotic LN with peripheral
(eggshell) calcification
• PMF nodules >2 cm dia+ silicosis
Microscopy
• Concentric hyalinized collagen
surrounded by condensed
collagen,fibroblasts & lymphocytes.
• Birefringent silica particles
(polarized light)
• Nodules incorporate normal lung
tissue into themselves.
Clinical features
• Early :X Ray fine nodularity in upper zones of
lungs. Eggshell calcification in hilar LN
• PFT normal/moderately affected initially
• PMF: Progressive disease even after exposure
stopped.
• X ray nodules >2 cm dia.
• PFT markedly ↓
• Associated tuberculosis (↓CMI)
• Carcinogenic ??
Prevention
• Air handling equipment in work place
• Use of face masks.
Asbestos related
diseases
• Fibrous plaques-focal/diffuse
• Pleural effusion
• Parenchymal interstitial fibrosis
(asbestosis-diffuse interstitial
process)
• Lung carcinoma
• Malignant Mesothelioma
•
Extrapulmonary malignancieslarynx,?colon
Asbestos related disease
• Asbestos = unquenchable
• Asbsetos is resistant to physical and
chemical destruction and is
therefore used for fire proofing,
insulation, brake lining etc.
• Construction material
• Ship demolition industry
Forms of asbestos
•
•
•
•
Serpentine
Curly,more used in
industry e.g.chrysotile.
less pathogenic
Breaks into fragments
Fibrogenic
• Impacts in upper
airways & removed by
mucociliary apparatus &
more soluble-leached
out
• Not associated with
mesothelioma
•
•
•
•
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Amphibole
straight & stiff
e.g. crocidolite
more pathogenic
Resists breaking into
fragments
Fibrogenic
Align in airstream & go
deep ,penetrate
epithelium,enter
interstitium
<0.5 μm thick,>8 μm long
more fibrogenic
Associated with
mesothelioma
Pathogenesis
Fibrogenic potential like other inorganic
dusts
Tumour initiator and promoter
Asbestos fibers localized in distal airways
(close to mesothelium) release reactive
free radicals .
Absorption of carcinogens on asbestos
fibres e.g. smoking
Morphology
• Diffuse pulmonary interstitial
fibrosis
• Begins in the lower lobes &
subpleurally (silica &CWP >upper)
• Honeycomb lung
• Pleural plaques
Microscopy
• Interstitial fibrosis around respiratory
bronchioles and alveolar ducts, involves
adjacent alveoli
• Asbestos bodies –golden brown fusiform
or beaded rods with a tranluscent centre
(asbestos fibre coated by iron containing
proteinaceous material)
• Trapping & narrowing of pulmonary
arteries
Clinical course
• Dypsnoea
• Cough with sputum
• May progress to respiratory failure ,
cor pulmonale
• Cancer
Idiopathic pulmonary fibrosis
• This is characterised by diffuse
interstitial inflammation and fibrosis
resulting in severe hypoxemia and
cyanosis in the late stage
• Synonyms:-• Chronic interstitial pneumonitis
• Hamman-Rich Syndrome
• Cryptogenic fibrosing alveolitis
Pathogenesis
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Sequence of events:-Injury to alveolar wall
Interstitial oedema
Accumulation of inflammatory
cells(alveolitis)
• Type 1 pneumocytes injured
• Hyperplasia of type2 pneumocyte
• Proliferation of fibroblasts
Pathogenesis(contd.)
• Fibrosis of alveolar walls and alveolar
exudate
• Loss of architecture of lung
• Cause:-?immune mechanism
Morphology(contd..)
• END-STAGE:• Spaces lined by cuboidal /columnar
epithelium separated by
inflammatory fibrous tissue(Honeycomb lung)
• (end stage lung same in all conditions)

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