Lung Disease 1 (1) PDF

Lung 1  ATELECTASIS (COLLAPSE) Loss of lung volume caused by inadequate expansion of air spaces Three forms: Resorption atelectasis Compression atelectasis Contraction atelectasis  1-Resorption atelectasis: Occurs when an obstruction prevents air from...

Lung 1  ATELECTASIS (COLLAPSE) Loss of lung volume caused by inadequate expansion of air spaces Three forms: Resorption atelectasis Compression atelectasis Contraction atelectasis  1-Resorption atelectasis: Occurs when an obstruction prevents air from reaching distal airways Air already present gradually becomes absorbed, and alveolar collapse Depending on level of airway obstruction, an entire lung, a complete lobe, or one or more segments may be involved  The most common cause : Obstruction of a bronchus by a mucous or mucopurulent plug, frequently postoperatively Bronchial asthma Chronic bronchitis Tumor Foreign body aspiration, particularly in children  2-Compression atelectasis Passive or relaxation atelectasis Associated with accumulation of fluid, blood, or air within pleural cavity, mechanically collapses adjacent lung Pleural effusion, most commonly by (CHF) Pneumothorax Basal atelectasis : Resulting from failure to breath deeply commonly occurs in bedridden patients , with ascites, during and after surgery.  3-Contraction atelectasis Cicatrization atelectasis Occurs when local or generalized fibrotic changes in lung or pleura hamper expansion. OBSTRUCTIVE VS RESTRICTIVE PULMONARY DISEASES  (1) Obstructive (airway) disease: Characterized by limitation of airflow, usually resulting from an increase in resistance caused by partial or complete obstruction at any level (2) Restrictive disease: Characterized by reduced expansion of lung parenchyma accompanied by decreased total lung capacity  OBSTRUCTIVE LUNG (AIRWAY) DISEASES Emphysema Chronic bronchitis Bronchiectasis Asthma  COPD Definition of emphysema morphologic and radiologic features, whereas chronic bronchitis defined on basis of clinical features Chronic bronchitis initially involves large airways, whereas emphysema affects acinus In severe or advanced cases of both, small airway disease (chronic bronchiolitis) characteristic.  1-Emphysema Abnormal permanent enlargement of air spaces distal to terminal bronchioles + destruction of walls without significant fibrosis Classified to anatomic distribution within lobule Acinus: structure distal to terminal bronchioles Lobule: a cluster of 3-5 acini  A-Centriacinar (Centrilobular) Emphysema Central/proximal parts of acini respiratory bronchioles affected, while distal alveoli spared Both emphysematous and normal air spaces exist within same acinus and lobule More common and severe in upper lobes, particularly in apical segments Most commonly seen a consequence of Cigarette smoking  B-Panacinar (Panlobular) Emphysema Acini uniformly enlarged, from level of respiratory bronchiole to terminal blind alveoli More commonly in lower lung zones Occurs in α1-antitrypsin deficiency  C-Distal Acinar (Paraseptal) Emphysema Proximal portion of acinus normal but distal part primarily involved More striking adjacent to pleura, along lobular connective tissue septa, and at margins of lobules, adjacent to areas of fibrosis , scarring or atelectasis More severe in upper half of lungs  Bullae : Multiple, contiguous, enlarged air spaces 2.0 cm, sometimes forming cystic structures , with progressive enlargement Most often in cases of spontaneous pneumothorax in young adults.  D-Irregular Emphysema Clinically asymptomatic , may be the most common form of emphysema Acinus irregularly involved Invariably associated with scarring, resulting from healed inflammatory diseases PATHOGENESIS  Clinical Features Dyspnea : usually the first symptom Barrel chested and dyspneic , with obviously prolonged expiration “Pink puffers” Because of prominent dyspnea and adequate oxygenation of hemoglobin  2-Chronic Bronchitis Persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Common among cigarette smokers and urban dwellers in smog- ridden cities “Blue bloaters”: cyanosis  Most important cause : Cigarette smoking Other air pollutants, as sulfur dioxide and nitrogen dioxide MORPHOLOGY Enlargement of mucus-secreting glands in trachea and larger bronchi (mucus hypersecretion) Thickness of submucosal gland layer / bronchial wall (Reid index: normally 0.4) Inflammatory cells, largely mononuclear + neutrophils, in bronchial mucosa (eosinophils not seen )  Morphologic basis of airflow obstruction in chronic bronchitis results from: (1) Small airway disease (2) Coexistent emphysema  Chronic bronchiolitis (small airway disease): Goblet cell metaplasia Mucous plugging Inflammation, and fibrosis Bronchiolitis obliterans: Submucosal fibrosis luminal narrowing and airway obstruction  3-Asthma Chronic inflammatory disorder of airways causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning.  Pathogenesis “Hygiene hypothesis,” According to eradication of infections may alter immune homeostasis and promote allergic and other harmful immune responses. Genetic predisposition to type I hypersensitivity (atopy) Acute and chronic airway inflammation Bronchial hyperresponsiveness to a variety of stimuli  Atopic Asthma Most common type of asthma, usually beginning in childhood , type I IgE–mediated hypersensitivity reaction A positive family history of atopy and/or asthma common Asthmatic attacks often preceded by allergic rhinitis, urticaria, or eczema, Triggered by environmental antigens, as dusts, pollen, animal dander, and foods Skin test : an immediate wheal-and flare reaction  Atopic asthma: An excessive TH2 reaction against environmental antigens , produced Cytokines: IL-4 IgE production IL-5 eosinophils IL-13 mucus production and IgE production by B cells IgE coats submucosal mast cell on exposure to allergen, release granule contents , induces two waves of reaction:  Early reaction : Bronchoconstriction Increased mucus production Variable vasodilation  Late-phase reaction : Inflammation, with activation of eosinophils, neutrophils, and T cells. Airway remodeling “ Repeated of inflammation structural changes in bronchial wall, as : Hypertrophy of bronchial smooth muscle and mucus glands Increased vascularity Deposition of subepithelial collagen  The hallmarks of asthma: Intermittent, reversible airway obstruction Chronic bronchial inflammation with eosinophils Bronchial smooth muscle cell hypertrophy and hyperreactivity Increased mucus secretion.  Non-Atopic Asthma Asthma do not have evidence of allergen sensitization, skin test results negative A positive family history of asthma less common Respiratory infections due to viruses ( rhinovirus, parainfluenza virus) Inhaled air pollutants (sulfur dioxide, ozone, NO) (Eosinophils) common to both atopic and nonatopic variants of asthma  Drug-Induced Asthma Patients with aspirin sensitivity present with recurrent rhinitis and nasal polyps, urticaria , and bronchospasm Aspirin: Inhibits cyclooxygenase pathway of arachidonic acid metabolism without affecting lipoxygenase route, shifting balance of production toward leukotrienes cause bronchial spasm.  Occupational Asthma This form of asthma stimulated by : Fumes (epoxy resins , plastics) Organic and chemical dusts (wood, cotton, platinum), Gases (toluene), and other chemicals  MORPHOLOGY: Curschmann spirals: Tenacious Mucous plugs contain whorls of shed epithelium Numerous eosinophils Charcot-Leyden crystals : Collections of crystalloids made up of eosinophil proteins  Thickening of airway wall Sub-basement membrane fibrosis Increased vascularity in submucosa An increase in size of submucosal glands and goblet cell metaplasia of airway epithelium Hypertrophy and/or hyperplasia of bronchial muscle  4-Bronchiectasis Permanent dilation of bronchi and bronchioles caused by destruction of muscle and supporting elastic tissue associated with chronic necrotizing infections Cough and expectoration of copious amounts of purulent sputum Diagnosis : Appropriate history +radiographic demonstration of bronchial dilation ❑ Conditions predispose to bronchiectasis : Bronchial obstruction: Tumors, foreign bodies, and occasionally impaction of mucus Congenital or hereditary conditions: Cystic fibrosis In immunodeficiency states: immunoglobulin deficiencies Primary ciliary dyskinesia (immotile cilia syndrome): AR disorder associated with bronchiectasis and sterility in males Necrotizing, or suppurative pneumonia: Staphylococcus aureus or Klebsiella spp  PATHOGENESIS: Obstruction Chronic infection MORPHOLOGY: Usually lower lobes bilaterally When caused by tumors or aspiration of foreign bodies involvement may be sharply localized to a single segment of lungs.  Histologic findings: In active case: An intense acute and chronic inflammatory exudate within walls of bronchi and bronchioles Desquamation of lining epithelium Staphylococci, streptococci, pneumococci, enteric organisms, anaerobic and microaerophilic bacteria, and (particularly in children) Haemophilus influenzae and Pseudomonas aeruginosa.  In chronic cases: Fibrosis of bronchial and bronchiolar walls and peribronchiolar fibrosis develop In some instances :necrosis destroys bronchial/bronchiolar walls, producing an abscess cavity.  Complications of bronchiectasis: Cor pulmonale Metastatic brain abscesses Reactive amyloidosis  Restrictive defect occurs in two general conditions: (1) chest wall disorders in presence of normal lungs Severe obesity, diseases of pleura, and neuromuscular disorders, as Guillain-Barré syndrome (2) Acute or chronic interstitial lung diseases Acute restrictive disease : ARDS Chronic restrictive diseases : pneumoconiosis , interstitial fibrosis and infiltrative conditions (sarcoidosis)  Acute Respiratory Distress Syndrome Respiratory failure occurring within 1week of a known clinical insult with bilateral opacities on chest imaging, not fully explained by effusions, atelectasis, cardiac failure, or fluid overload Severe ARDS : Rapid onset of life-threatening respiratory insufficiency Cyanosis Severe arterial hypoxemia , refractory to oxygen therapy  Diffuse alveolar damage (DAD): Histologic manifestation of ARDS in lungs primary pulmonary diseases and severe systemic inflammatory disorders as sepsis Pneumonia Aspiration Trauma (brain injury,abdominal surgery, and multiple fractures) Pancreatitis Transfusion reactions  Pathogenesis Increased synthesis of (IL-8) , a potent neutrophil chemotactic and other factors, as IL-1 and (TNF), , by pulmonary macrophages Neutrophils : An important role in the pathogenesis of ARDS Activated neutrophils release a variety of products , cause damage to alveolar epithelium and endothelium  Integrity of alveolar-capillary membrane compromised by endothelial and epithelial injury.  MORPHOLOGY Acute phase of ARDS: The most characteristic finding : Hyaline membranes: Fibrin-rich edema fluid + necrotic epithelial cells Capillary congestion , necrosis of alveolar epithelial cells ,interstitial and intraalveolar edema and hemorrhage, and collections of neutrophils in capillaries Most patients who survive acute insult recover normal respiratory function within 6-12 months  In organizing stage: Proliferation of type II pneumocytes (regenerate alveolar lining) Intra-alveolar fibrosis Proliferation of interstitial cells and deposition of collagen lead to thickening of septum  CHRONIC INTERSTITIAL (RESTRICTIVE, INFILTRATIVE) LUNG DISEASES Bilateral, often patchy, pulmonary fibrosis mainly affecting walls of alveoli Categorized based on : clinicopathologic features characteristic histology  Interstitium: Composed of basement membrane of endothelial and epithelial cells , collagen fibers, elastic tissue, fibroblasts, a few mast cells, and occasional mononuclear cells Hallmark feature : Reduced compliance , stiff lungs ; necessitates increased effort to breathe (dyspnea) 1-Fibrosing Diseases  Idiopathic Pulmonary Fibrosis:(IPF) Cryptogenic fibrosing alveolitis Patchy , progressive bilateral interstitial fibrosis Males > females > 50 years of age  Gradual onset of a nonproductive cough and progressive dyspnea Characteristic “dry” or “Velcro”-like crackles during inspiration Cyanosis, cor pulmonale , and peripheral edema in later stages of disease.  PATHOGENESIS: “Repeated cycles” of epithelial injury and defective repair of alveolar epithelium, often in a genetically predisposed individual Chronic gastroesophageal reflux TGF-β1, from injured type I pneumocytes induces excessive fibroblastic or myofibroblastic proliferation characteristic fibroblastic foci  MORPHOLOGY: Fibrosis (firm, rubbery white areas), with lower lobe predominance Histologic hallmark of UIP: Patchy interstitial fibrosis , varies in intensity and existence of both early and late lesions Earliest lesions exuberant fibroblastic foci Over time become more collagenous and less cellular.  Clinical and radiologic findings often diagnostic Radiologic and histologic pattern of fibrosis as usual interstitial pneumonia (UIP),required for diagnosis of IPF Similar pathologic changes in lung as asbestosis, and collagen vascular diseases must be ruled out before appellation of idiopathic used  Interstitial inflammation usually patchy and mostly lymphocytes and occasional plasma cells, mast cells, and eosinophils Honeycomb fibrosis: Dense fibrosis causes collapse of alveolar walls and formation of cystic spaces  2-Nonspecific interstitial pneumonia (NSIP) Chronic bilateral interstitial lung disease of unknown etiology Association with collagen vascular disorders as rheumatoid arthritis. Important to recognize NSIP because much better prognosis than IPF Mild-moderate interstitial chronic inflammation and/ or fibrosis patchy but uniform in areas involved  3-Cryptogenic Organizing Pneumonia Patients present with cough and dyspnea Chest radiographs: Subpleural or peribronchial patchy areas of airspace consolidation due to intraalveolar plugs of loose organizing connective tissue.  4-Pneumoconioses: A term originally describe lung disorders caused by inhalation of mineral dusts (organic and inorganic particulates) Three most common result from exposure to coal dust, silica, and asbestos , stem from exposure in workplace  Silica , asbestos, and beryllium more reactive than coal dust, resulting in fibrotic reactions at lower concentrations Pulmonary alveolar macrophage : key cellular element in initiation and perpetuation of lung injury and fibrosis Tobacco smoking worsens effects of all inhaled mineral dusts, more so with asbestos  A-Coal Worker’s Pneumoconiosis Pulmonary anthracosis: Pulmonary lesion in coal miners and commonly seen in all urban dwellers and tobacco smokers. Inhaled carbon pigment engulfed by alveolar or interstitial macrophages  Simple CWP : (anthracite mining) Coal macules and larger coal nodule. Coal macule consists of dust-laden macrophages and small amounts of collagen fibers arrayed in a delicate network Upper lobes and upper zones of lower lobes more heavily involved Centriacinar emphysema  Complicated CWP (PMF): Occurs on a background of simple CWP by coalescence of coal nodules Multiple, intensely blackened scars >2 cm, sometimes to 10 cm Pulmonary dysfunction, pulmonary hypertension, and cor-pulmonale  PMF has a tendency to progress even in the absence of further exposure. Once smoking-related risk , no increased frequency of lung carcinoma in coal miners, a feature distinguishes CWP from both silica and asbestos exposures  B-Silicosis: Most prevalent chronic occupational disease in the world Inhalation of crystalline silica, mostly in occupational settings in sandblasting and hard-rock mining Silica : Crystalline (quartz), far the most toxic and fibrogenic Amorphous forms  MORPHOLOGY: Silicotic nodules in upper zones of lungs Microscopically: Concentrically arranged hyalinized collagen fibers surrounding an amorphous center “Whorled” appearance of collagen fibers distinctive for silicosis Polarized microscopy : Weakly birefringent silica particles, primarily in center of nodules.  Clinical Features: On routine chest radiographs obtained in asymptomatic workers Radiographs : fine nodularity in upper zones of lung Most patients do not develop shortness of breath until late in the course, after PMF present Pulmonary hypertension and cor pulmonale  Silicosis associated with an increased susceptibility to tuberculosis. Nodules of silicotuberculosis often contain a central zone of caseation. Relationship between silica and lung cancer has been associated with some increase in risk  C-Asbestosis and Asbestos- Related Diseases: Occupational exposure to asbestos : (1) Parenchymal interstitial fibrosis (asbestosis) (2) Localized fibrous plaques or, rarely, diffuse fibrosis in pleura (3) Pleural effusions (4) Lung carcinomas (5) Malignant pleural and peritoneal mesotheliomas (6) Laryngeal carcinoma.  MORPHOLOGY: In contrast with CWP and silicosis, asbestosis begins in lower lobes and subpleura Asbestosis : Diffuse pulmonary interstitial fibrosis. Asbestos bodies: Golden brown, fusiform or beaded rods with a translucent center Consist of asbestos fibers + iron-containing proteinaceous material  Pleural plaques : Most common manifestation of asbestos exposure Usually asymptomatic , detected on radiographs as circumscribed densities most frequently on anterior/posterolateral aspects of parietal pleura and over domes of diaphragm Well-circumscribed plaques of dense collagen ,often containing calcium  Clinical Features: Risk of lung carcinoma increased about five-fold for asbestos workers Relative risk for mesothelioma >1000 times greater An increased incidence of asbestos-related cancers in family members of asbestos workers Concomitant cigarette smoking greatly increases risk of lung carcinoma but not mesothelioma.  Drug- and Radiation-Induced Pulmonary Diseases Bleomycin Amiodarone Radiation pneumonitis : Complication of irradiation of pulmonary and other thoracic tumors Acute radiation pneumonitis: 1-6 months after therapy in 20% of patients Fever, dyspnea out of proportion to volume of irradiated lung, pleural effusion, and pulmonary infiltrates in irradiated lung bed