L6, Resp Pathology PDF

pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN LECTURE (6) INTERSTITIAL LUNG DISEASE (ILD) & DISEASES OF VASCULAR ORIGIN Dr. M. Shalaby pathology - respiratory ILD & DIS...

pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN LECTURE (6) INTERSTITIAL LUNG DISEASE (ILD) & DISEASES OF VASCULAR ORIGIN Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Group of disorders having generalized involvement of lung interstitium. DEFINITION :  200 different diseases of multiple etiologies  These disorders are labelled as ILD because of the common clinical, radiological and histological manifestations  Fibrosing : ① Usual interstitial pneumonia (idiopathic pulmonary fibrosis) ② Nonspecific interstitial pneumonia ③ Cryptogenic organizing pneumonia ④ Connective tissue disease–associated Pneumoconiosis ⑤ Drug reactions ⑥ Radiation pneumonitis CATEGORIES OF  Granulomatous : CHRONIC ILD : ① Sarcoidosis ② Hypersensitivity pneumonitis  Eosinophilic :  Pulmonary eosinophilia  Smoking related interstial lung diseases ① Desquamative interstitial pneumonia ② Respiratory bronchiolitis interstitial lung disease ③ Langerhans cell histiocytosis Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Clinico-pathologic syndrome marked by progressive interstitial DEFINITION: pulmonary fibrosis and respiratory failure.  While the cause of IPF remains unknown, it appears that it arises in genetically predisposed individuals who are prone to aberrant repair PATHOGENESIS: of recurrent alveolar epithelial cell injuries caused by environmental exposures, usually present in older adult PATHOLOGY:  Pleural surfaces of lung are cobblestoned as a result of the retraction of scars along the interlobular septa. N/E  Cut surface: shows firm, rubbery white areas of fibrosis, which occurs preferentially in the lower lobes, the subpleural regions.  The hallmark is patchy interstitial fibrosis: Varies in intensity and age.  The earliest lesions contain exuberant proliferation of fibroblasts (fibroblastic foci).  With time these areas become more fibrotic and less cellular.  Quite typical is the coexistence of both early and late lesions.  The dense fibrosis causes the destruction of alveolar architecture and M/E the formation of cystic spaces lined by hyperplastic type II pneumocytes or bronchiolar epithelium (honeycomb fibrosis).  There is mild to moderate inflammation within the fibrotic areas, consisting of mostly lymphocytes admixed with a few plasma cells, neutrophils, eosinophils, and mast cells.  Foci of In acute exacerbations, diffuse alveolar damage may be superimposed Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN NORMAL LUNG- CUT SURFACE AND PLEURA SMOOTH & HOMOGENOUS USUAL INTERSTITIAL PNEUMONIA. IPF- CUT SURFACE DEMONSTRATES PATCHY INVOLVEMENT OF LUNG THE FIBROSIS IS MORE WITH fiBROUS SCARRING AROUND DILATED AIRSPACES FORMING A PRONOUNCED IN THE SUBPLEURAL HONEY COMB PATTERN REGION.  IPF begins insidiously with gradually increasing dyspnea on exertion and dry cough. CLINICAL  Most patients are 55 to 75 years old at presentation. FEATURES OF  Hypoxemia, cyanosis, and clubbing occur late in the course. IPF  The course in individual patients is unpredictable.  Usually there is slowly progressive respiratory failure. Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Same as IPF although patients tend to be women, younger in age who never smoked.  Often associated with: ① Connective tissue disease CLINICAL ② Hypersensitivity pneumonitis FEATURES ③ HIV infection.  Lung biopsy may be required for Dx.  Prognosis better than IPF.  Fibroblastic foci and honeycombing are typically absent.  Most often seen as a response to infection or inflammatory injury of DEFINITION: lungs.  Associated with viral and bacterial pneumonias  Cough and dyspnea DIAGNOSIS  Have patchy subpleural or peribronchial areas of airspace consolidation radiographically.  Characterized by the presence of polypoid plugs of loose organizing connective tissue (fibrous tissue) (Masson bodies). HISTOLOGICALLY Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Encompass as a group of chronic fibrosing diseases of lung. DEFINITION:  Resulting from exposure to organic and inorganic particles Most commonly mineral dust.  Mineral Dusts ① Silica → Silicosis ② Asbestos → Asbestosis LUNG DISEASES  Organic Dusts That Induce Hypersensitivity Pneumonitis CAUSED BY AIR Moldy hay → Farmer’s lung POLLUTANTS  Organic Dusts That Induce Asthma Chemical Fumes Vapors ① COAL WORKERS PNEUMOCONIOSIS  The most innocuous coal-induced pulmonary lesion in coal miners ANTHRACOSIS  Also seen to some degree in tobacco smokers.  Characterized by coal macules (1 to 2 mm in diameter) and larger coal nodules. SIMPLE COAL  Coal macules consist of carbon-laden macrophages. WORKERS’  Nodules also contain a delicate network of collagen fibers. PNEUMOCONIOSIS  Although these lesions are scattered throughout the lung, Upper lobes and upper zones are mostly affected. COMPLICATED  Progressive massive fibrosis: COAL WORKERS’ Occurs on a background of simple disease and generally requires PNEUMOCONIOSIS many years to develop. Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN ② SILICOSIS  Common lung disease caused by inhalation of proinflammatory DEFINITION crystalline silicon dioxide (silica).  In early stages: Tiny, barely palpable, discrete pale to blackened nodules in hilar lymph nodes and upper zones of GROSSLY lungs.  As the disease progresses: These nodules coalesce into hard, collagenous scars. MICROSCOPICALLY  Concentrically arranged hyalinized collagen fibers  Many patients are asymptomatic  Shortness of breath  late presentation: Abnormal pulmonary function, pulmonary CLINICAL PICTURE hypertension & cor pulmonale  ↑ susceptibility to T.B.  ↑ risk of lung cancer with crystalline silica ③ ASBESTOS-RELATED DISEASES  Family of proinflammatory crystalline hydrated silicates that are DEFINITION associated with pulmonary fibrosis and various forms of cancer  Marked by diffuse pulmonary interstitial fibrosis, which is MORPHOLOGY distinguished from diffuse interstitial fibrosis resulting from other causes only by the presence of asbestos bodies ASBESTOS-RELATED PLEURAL PLAQUES. LARGE, DISCRETE FIBROCALCIFIC PLAQUES ARE SEEN ON ASBESTOS BODIES PLEURAL SURFACE OF THE DIAPHRAGM. Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Virtually every organ in body has been described as being affected by sarcoidosis, at least on rare occasions.  Involved tissues contain well-formed non-necrotizing granulomas composed of aggregates of tightly clustered epithelioid macrophages, often with giant cells. MORPHOLOGY  Central necrosis is unusual.  With chronicity the granulomas may become enclosed within fibrous rims or may eventually be replaced by hyaline fibrous scars.  Laminated concretions composed of calcium and proteins known as Schaumann bodies and stellate inclusions known as asteroid bodies are found within giant cells in approximately 60% of the granulomas. BRONCHUS WITH CHARACTERISTIC NONCASEATING SARCOIDAL GRANULOMAS WITH MANY SCHAUMANN BODIES AND ASTEROID BODIES MULTINUCLEATED GIANT CELLS. NOTE: SUBEPITHELIAL LOCATION OF GRANULOMAS. Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Spectrum of immunologically mediated, predominantly interstitial MORPHOLOGY lung disorders caused by intense, often prolonged exposure to inhaled organic antigens.  Depend on the phase of the disease: ① Acute alveolar damage is seen in 1st hours and few days after antigen exposure. HISTOLOGIC ② Subacute changes are characteristically centered on bronchioles. CHANGES  They include: Interstitial pneumonitis, consisting primarily of Cytotoxic T lymphocytes, plasma cells, and macrophages ① Clinical: wheezes in hypersensitivity pneumonitis, eosinophilic pneumonia or sarcoidosis ② Systemic, dermatologic or ophthalmologic symptoms ③ Occupational exposure ④ Radiology ⑤ Bronchoscopy (BAL, transbronchial biopsy). ⑥ Video assisted thoracoscopic biopsy:  Allows pathological classification  Standard for Dx. Of ILD  Should be done under 60 yrs of age ⑦ Pulmonary Function Tests:  Restrictive defect on spirometery.  Tidal volumes are small  Vital capacity/Total lung capacity-reduced.  Reduced diffusing capacity/Arterial hypoxemia - observed in late stage. ⑧ Distribution of ILD UPPER LUNG ZONE LOWER LUNG ZONE ① Sarcoidosis ① UIP / IPF ② Hypersensitivity pneumonitis ② Asbestosis Dr. M. Shalaby  pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN ⑨ Patterns of ILD PERIPHERAL RETICULAR GROUND GLASS NODULAR CYSTIC  IPF  Hypersensitivity  Sarcoidosis  Langerhans cell pneumonitis histiocytosis  Sarcoidosis  Lymphocytic interstitial pneumonia  Recognition of a predominantly inflammatory cellular pattern (increased lymphocytes, eosinophils, or neutrophils) in the BAL differential cell profile frequently helps the clinician narrow the differential diagnosis of ILD.  Disorders associated with increased percentage of specific BAL cell type:  >15% lymphocytes LYMPHOCYTIC  Sarcoidosis (CD4+/CD8+ratio >4 is highly specific for sarcoidosis CELLULAR  Non specific interstitial pneumonia PATTERN  Cryptogenic organizing pneumonia  >1% eosinophils EOSINOPHILIC  Asthma CELLULAR  Eosinophilic pneumonia PATTERN  Allergic bronchopulmonary aspiragillosis NEUTROPHILIC  >3% neutrophils CELLULAR  Idiopathic pulmonary fibrosis PATTERN  Asbestosis Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN  Important cause of morbidity and mortality, particularly in patients INTRODUCTION who are bedridden.  Mainly arises from recent thrombi of calf veins in lower limbs (Most SOURCES OF common). EMBOLUS  Thrombi in Rt. side of heart e.g. in cases of Rt. sided heart failure ① Large embolus: Occludes pulmonary trunk or one of its main branches produces sudden death (no time for infarction). ② Medium sized emboli: If the lung is healthy, no effect will occur as the lung has double EFFECTS blood supply (pulmonary and bronchial arteries). If the lung suffering from chronic venous congestion, lung infract occurs. ③ Recurrent small sized emboli: Produce pulmonary hypertension due to lung fibrosis and right – sided heart failure (cor-pulmonale) Dr. M. Shalaby pathology - respiratory ILD & DISEASES OF VASCULAR ORIGIN DEFINITION  Mean pulmonary artery pressure ≥to 25 mm Hg at rest. ① Pulmonary arterial hypertension, a diverse collection of disorders that all primarily impact small pulmonary muscular arteries. ② Pulmonary hypertension due to left heart failure. WHO ③ Pulmonary hypertension due to lung diseases and/or hypoxia. CLASSIFICATION ④ Chronic thromboembolic pulmonary hypertension and other obstructions. ⑤ Pulmonary hypertension with unclear and/or multifactorial mechanisms. DEFINITION  Dramatic complication of some interstitial lung disorders. ① Goodpasture syndrome:  = Anti–Glomerular Basement Membrane Antibody Disease With Pulmonary Involvement)  Uncommon autoimmune disease in which kidney and lung injury are caused by circulating autoantibodies against the noncollagenous domain of the α3 chain of collagen IV ② Idiopathic pulmonary hemosiderosis:  Rare disorder characterized by intermittent, diffuse alveolar INCLUDE hemorrhage.  Most cases occur in young children.  It usually presents with insidious onset of productive cough, hemoptysis, and anemia associated with diffuse pulmonary infiltrates.  The cause & pathogenesis are unknown, and anti– basement membrane antibodies (Ig G) are undetectable. ③ Vasculitis-associated hemorrhage. Dr. M. Shalaby