Clinical features 1. Dyspnoea 2. Tachypnoea 3. Cyanosis 4. No wheezing
Pneumoconiosis• Lung disease caused by inhalation of dust• Synonyms: • Dust diseases • Occupational lung diseases• Dusts –Inert Predispose to TB Predispose to neoplasia
Factors determining - disease1. Size / shape of particles2. Solubility3. Amount of dust retained in lungs4. Effect of other irritants - ex Smoke5. Host factors: Clearance mechanism Immune status
Size of dust• Particles larger than 5µm may reach – Terminal airway – Ingestion by alveolar macrophage• Smaller than 1µm may – Reach alveoli – Stimulate macrophage – Result in fibrosis
In the nose, the hair at the externalnares filter out the larger particles,trapping almost all particles larger than5µm.In the trachea and bronchi, 90% of theparticles larger than 3-5µm are caught.Particles between 0.5 and 2µm reachthe alveolar ducts and alveoli.
Solubility and cytotoxicity• Smaller particles: – Pulmonary fluid – Rapid toxic levels – Cause acute lung injury• Larger particles: – Resist dissolution – Persist in lung for years – Evoke fibrosis ex silicosis
Physiochemical reactivity• Quartz particles• Direct injury to tissue and cell membrane• Can trigger proinflammatory / profibrosing reaction
Systemic response• Particles reach LN by macrophages• Initiate immune response / amplifies local reaction• Particles translocate to blood• Evokes systemic inflammation.
Host tissue response1. Fibrous nodules ex coal workers pneumoconiosis, silicosis.2. Interstitial fibrosis ex asbestosis.3. Hypersensitivity ex.berylliosis.
Complicated CWP [PMF]• Confluence of fibrosing reaction in lung that is a complication of any pneumoconiosis• Common in CWP• Can also be seen in silicosis
Anthracosis• Coal - Innocuous• Common in urban dwellers/smokers• Carbon pigment in lung, lymphatics, LN• Autopsy: linear streaks and aggregates in pul. lymphatics, LNs
Simple CWP• Coal macule: 1 to 2 mm, carbon laden macrophages• Coal nodules: larger than macule, contain delicate collagen fibres• Upper lobes, upper zones of lower lobes heavily involved• Located adjacent to resp bronchioles- initial dust deposition site-centrilobular emphysema
Complicated CWP (PMF) In a background of simple CWP Over years Intensely blackened scars Larger than 2 cms May be upto 10 cms Multiple,bilateral,involve upper,post region Micro: dense collagen, pigment, necrotic centre,with local ischemia
Caplan syndrome (Rheumatoid pneumoconiosis)• Development of rheumatoid arthritis in CWP, silicosis, asbestosis• Gross; round, firm nodules with central necrosis, cavitation or calcification• Micro: central zone of dust laden fibrinoid necrosis enclosed by palisading fibroblasts and mononuclear cells
Clinical features• Cough with jet black sputum• Dyspnoea• Pul-HT, cor pulmonale• TB and RA are more common in miners• Increased risk for Ca. stomach• Bronchogenic .ca is rare
Figure 15-18 Progressive massivefibrosis superimposed on coalworkers pneumoconiosis. The large,blackened scars are locatedprincipally in the upper lobe. Note theextensions of scars into surroundingparenchyma and retraction ofadjacent pleura.
Silica – Physical formsCrystalline forms Amorphous forms• Quartz • Talc• Crystobalite • Vermiculite• Tridymite • Mica• Are fibrogenic • Less fibrogenic
IARC pointed out that only crystalline form is actually carcinogenic
Pathogenesis - Silicosis• Silica - macrophage ingestion - direct toxic effect• Silica particles - activation and release of mediators by viable macrophages• IL-1, TNF, fibronectin, lipidmediators, oxygen derived free radicles, fibrogenic cytokines• Mixed with other minerals, quartz has less fibrogenic effect. ex: hematite.
Gross pathology• Silicotic lung studded with well circumscribed hard, fibrotic nodules,1 to 5 mm in diameters• Scattered throughout the lung• Simultaneous deposition of coal dust with calcification• Pleura thickened, adherent to chest wall• Similar nodules in LN, pleura
Gross pathology contd…,• X ray nodular lesions - egg shell shadows• Lesion – necrosis, cavitation• Complicated by TB, rheumatoid pneumoconiosis.
FIGURE 15-18Advanced silicosisScarring has contractedthe upper lobe into asmall dark mass (arrow).Note the dense pleuralthickening.
Microscopy of silicosis• Nodular lesions- concentric layers of hyalinised collagen surrounded by dense capsule of more condensed collagen• Polarising microscopy --- birefringent silica particles.
Figure 15-19 Advanced silicosis seen on transection of lung. Scarring hascontracted the upper lobe into a small dark mass (arrow). Note the densepleural thickening.Figure 15-20 Several coalescent collagenous silicotic nodules.
Figure 15-20 Several coalescent collagenous silicotic nodules.
Pneumoconiosis: polarized light microscopy - silica crystals.Here are seen bright white crystals of varying sizes.
Bright white collections of polarizable crystals are seen here, but are diffuse and centeredaround vascular spaces. This is the lung of a patient with a long history of intravenous drug use
Clinical features-silicosis Asymptomatic- routine chest x ray X ray- fine nodularity in upper zones Pulm functions –normal/mildly affected. Slow to kill but impaired pulm fn severely limits activity. Depresses CMI Increased susceptibility to TB Crystalline silica - occupational source of carcinogen.