PneumoconiosisPneumoconiosisPneumoconiosisPneumoconiosis

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 macrophages-phagocytosis 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)

• 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• 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 malignancies-

larynx,?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

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

PathogenesisFibrogenic potential like other

inorganic dustsTumour initiator and promoterAsbestos 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• 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(Honey-comb lung)

• (end stage lung same in all conditions)