Strength is Life Weakness is Death
Swami Vivekananda
Lung - Pathology
Diffuse Interstitial (Restrictive) Diseases
Fibrosing Granulomatous Eosinophilic Smoking-Related Other
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Diffuse Interstitial (Restrictive) Diseases Heterogeneous group 15% of noninfectious pulmonary diseases Unknown cause and pathogenesis Lead to Diffuse and usually chronic involvement of the lung • End-stage lung or Honeycomb lung
Lung – Pathology
Diffuse Interstitial (Restrictive) Diseases
Fibrosing
Usual interstitial pneumonia (idiopathic pulmonary fibrosis)
Nonspecific interstitial pneumonia Cryptogenic organizing pneumonia
collagen vascular diseases Pneumoconiosis
Complications of Therapies
• Collagen Vascular Diseases (SLE, RA, Systemic sclerosis (scleroderma)
• Pulmonary involvement indicates poor prognosis
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SLE - patchy, transient parenchymal infiltrates Systemic sclerosis – NSIP (Nonspecific interstitial pneumonia ) Rheumatoid arthritis (RA) Pulmonary
• diffuse interstitial pneumonitis and fibrosis • intrapulmonary rheumatoid nodules; • pulmonary hypertension
• Pleural
• chronic pleuritis, Effusions, pleural nodules
Lung – Pathology Diffuse Interstitial (Restrictive) Diseases
Fibrosing
Pneumoconioses
Coal worker’s Pneumoconiosis (CWP)
Silicosis
Asbestos-Related Diseases
• Pneumoconiosis
• • • • Lung reaction to inhalation of mineral dusts in the workplace organic & inorganic particulates chemical fumes and vapors General Pathogenesis – most dangerous particles of size range from 1 to 5 μm
• Coal workers‘ pneumoconiosis (CWP)
• 1. 2. 3. Disease spectrum of coal dust-induced disease Asymptomatic Anthracosis Simple coal workers' pneumoconiosis (CWP) Complicated CWP, or progressive massive fibrosis (PMF) Pathogenesis: incompletely understood Affect mainly upper lobes Cause : In most cases -carbon dust Clinical Course benign disease But in PMF patients – progressive – Develop pulmonary dysfunction, pulmonary HTN & Cor Pulmonale No ↑ risk of TB or cancer ↑ incidence of chronic bronchitis, Centrilobular emphysema
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Morphology Coal workers‘ pneumoconiosis (CWP)
Feature Anthracosis Simple CWP Complicated CWP
clinical
Asymptomatic
symptomatic
symptomatic
lung function
Normal
Normal
Compromised
Morphology
innocuous lesion
coal macules (1 to 2 mm Macrophages)
Multiple blackened scars from 2 - 10 cm (Necrosis )
COAL WORKERS‘ PNEUMOCONIOSIS (CWP)
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Silicosis MC chronic occupational disease in the world caused by inhalation of crystalline silicon dioxide (silica). Acute silicosis -accumulation of a lipoproteinaceous material within alveoli Chronic silicosis - slowly progressing, nodular, Fibrosing pneumoconiosis Pathogenesis crystalline forms -more fibrogenic (quartz –worst) silica particles lung macrophages ingest them activation and release of mediators IL-1, TNF, oxygen-derived free radicals Anti-TNF monoclonal antibodies can block lung collagen accumulation in mice Morphology. – Early stages –tiny nodules in the upper zones – disease progresses –nodules coalesce into hard, collagenous scars central softening and cavitation (due to superimposed tuberculosis or to ischemia) – X-ray – egg shell calcification in the lymph nodes – Advanced stage - PMF Histology Nodular lesions -concentric layers of hyalinized collagen surrounded by a dense capsule Birefringent silica particles in polarized microscopy
Silicosis
• Asbestos-Related Diseases
• • • • • • • • • • • • • • • Localized fibrous plaques or diffuse pleural fibrosis Pleural effusions Parenchymal interstitial fibrosis (asbestosis) Lung carcinoma Mesotheliomas Laryngeal and extra pulmonary neoplasms, (colon carcinomas) Two forms of asbestos serpentine (curly and flexible fibers) most of the asbestos used in industry amphibole (straight, stiff, and brittle fibers). induction of malignant pleural tumors (mesotheliomas) Asbestosis – diffuse pulmonary interstitial fibrosis, Asbestos bodies or Ferruginous bodies golden brown, fusiform or beaded rods macrophages engulf of asbestos fibers coated with an iron-containing proteinaceous material
• Pathogenesis.
• Morphology.
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Asbestos & Neoplasms act as a tumor initiator & tumor promoter. Oncogenic effects mediated by 1. reactive free radicals generated by asbestos fibers (localize in the distal lung & close to the mesothelial layers) 2. chemicals adsorbed onto the asbestos fibers – Example- tobacco smoke Lung involvement Begins as fibrosis around respiratory bronchioles and alveolar ducts Extends to adjacent alveolar sacs and alveoli. Eventually - honeycombed. In contrast to CWP and silicosis, Begins in the lower lobes and subpleurally. middle and upper lobes affected later Pleural plaques MC manifestation of asbestos exposure MC site- anterior and posterolateral aspects of parietal pleura & domes of the diaphragm. not contain asbestos bodies always history of evidence of asbestos exposure.
Lung & Pleural involvement
Forms of asbestos
Feature Amphiboles Chrysotiles
Solubility
less soluble
more soluble
Nature
align themselves in the air stream & delivered into the lungs
more flexible, curled structure
Penetrability
penetrate epithelial cells and reach the interstitium
impacted and removed by the mucociliary elevator
Both are fibrogenic Both associated with ↑all asbestos-related disease except Mesothelioma
Asbestos-Related cancers
Feature lung carcinomas Mesotheliomas
Risk in asbestos workers
fivefold
> 1000-fold greater
Concomitant cigarette smoking
↑risk ( 55 fold)
No ↑risk
• Asbestos-Related Diseases • Complications
– Scarring trap pulmonary arteries and arterioles pulmonary HTN & Cor Pulmonale.
• Clinical Course.
• • • • • manifestations appear > 20 years of exposure Clinical findings - similar to other causes of diffuse interstitial lung disease Dyspnea - first manifestation accompanied by a cough associated with production of sputum. static or progress to respiratory failure, Cor Pulmonale, and death
• X-ray
• irregular linear densities- both lower lobes. • Later - honeycomb pattern
• Prognosis
• If lung or pleural cancer - grim prognosis