Transcript The Lung
The Lung Congenital Anomalies • Agenesis or hypoplasia of both lungs, one lung, or single lobes • Tracheal and bronchial anomalies (atresia, stenosis, tracheoesophageal fistula) • Vascular anomalies • Congenital lobar overinflation (emphysema) • Foregut cysts • Congenital pulmonary airway malformation • Pulmonary sequestrations Atelectasis (Collapse) • Incomplete expansion of the lungs or collapse of previously inflated lung • Three types – Resorption (obstruction) – Compression (e.g. tension pneumothorax) – Contraction Pulmonary Edema • Table 15-1 - Classification and Causes of pulmonary edema • Hemodynamic pulmonary edema – Heart failure cells, brown induration • Edema caused by microvascular injury Acute Lung Injury and Acute Respiratory Distress syndrome (Diffuse Alveolar Damage) • Acute lung injury (ALI) -abrupt onset of significant hypoxemia and diffuse pulmonary infiltrates in the absence of heart failure • Acute respiratory distress syndrome(ARDS) – severe ALI • Table 15-2 conditions associated with ARDS • Acute interstitial pneumonia –ALI of unknown etiology Acute Lung Injury • Diffuse alveolar damage, hyaline membranes • Integrity of the alveolar capillary barrier is compromised by endothelial, epithelial injury, or more commonly, both • Lung injury is caused by an imbalance of pro-inflammatory and anti-inflammatory mediators • Clinical – dyspnea and tachypnea, cyanosis and hypoxemia, respiratory failure, diffuse bilateral infiltrates, ventilationperfusion mismatch Obstructive vs Restrictive Diseases Obstructive Airway diseases Increase in resistance to airflow due to partial or complete obstruction Decreased FEV 1 Emphysema Chronic bronchitis Asthma Bronchiestasis Bronchiolitis Restrictive Reduced expansion of the lung parenchyma and decreased total lung capacity Chest wall disorders Neuromuscular ( e.g. polio) Kyphoscoliosis Pleural Disease Severe obesity Chronic interstitial and infiltrative disease Pulmonary fibrosis Pneumoconioses Granulomatous diseases Pulmonary Eosinophila Pulmonary alveolar Proteinosis Obstructive Pulmonary Disease • • • • Emphysema Chronic Bronchitis Asthma Bronchiectasis Emphysema • Irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis • Types – Centriacinar – Panacinar - alpha 1-antitrypsin deficiency – Distal acinar – spontaneous pneumothorax – Airspace enlargement with fibrosis (Irregular) Emphysema • Pathogenesis – Destructive effect of high protease activity in subjects with low antiprotease activity – Oxidant-antioxidant imbalance – Smoking Emphysema • Clinical – dyspnea, cough, wheezing, weight loss, expiratory airflow limitation (spirometry), pink puffers, death due to respiratory acidosis, right-sided heart failure, massive collapse of lungs secondary to pneumothorax • Other forms – Compensatory hyperinflation – Obstructive overinflation – Bullous emphysema – Interstitial emphysema Chronic Bronchitis • Persistent cough with sputum production for at least 3 months in at least 2 consecutive years, in the absence of any other identifiable cause • Table 15-4 Emphysema and chronic bronchitis • Pathogenesis – Long-standing irritation by inhaled substances – Hypersecretion of mucus, hypertrophy of glands, hyperplasia of goblet cells of small airways (Reid index) – Infection – secondary role – Blue-bloaters Asthma • Chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough particularly at night and/or early morning • Widespread but variable bronchoconstriction and airflow limitation, that is at least partially reversible • Increased airway responsiveness to a variety of stimuli, episodic bronchoconstrition, inflammation of the brochial walls, increased mucus secretion Asthma • Types – Atopic – type I IGE-mediated hypersensitvity – Non-atopic – viral-induced – Drug-induced - aspirin – Occupational – fumes, dust, chemicals Asthma • • • • Curschmann spirals Charcot-Leyden crystals Airway remodeling Clinical – dyspnea, tightness, wheezing, cough, status asthmaticus Bronchiectasis • Permanent dilation of bronchi and bronchioles caused by the destruction of the muscle and elastic tissue, resulting from or associated with chronic necrotizing infections • Dilated airways up to four times normal size • Mixed flora from bronchi • Clinical – severe, persistent cough, foul-smelling, sometimes bloody sputum, dyspnea and orthopnea Chronic Diffuse Interstitial (Restrictive) Diseases • • • • • Fibrosing diseases – Idiopathic Pulmonary fibrosis – Nonspecific interstitial pneumonia – Crytogenic Organizing pneumonia – Pulmonary involvement in the Connective tissue diseases – Pneumoconioses – Complications of therapies Granulomatous Diseases – Sarcoidosis – Hypersensitivity pneumonitis Pulmonary eosinophilia Smoking-related Interstitial diseases – Desquamative interstitial pneumonia – Respiratory Bronchioloiis –associated interstitial lung disease Pulmonary Alveolar Proteinosis Chronic Diffuse Interstitial Diseases • Inflammation and fibrosis of the pulmonary connective tissue, principally the most peripheral and delicate interstitium in the alveolar walls • Table 15-5 Major categories of chronic interstitial lung disease Fibrosing Diseases • Idiopathic pulmonary fibrosis – Also called cryptogenic fibrosing alveolitis – Caused by repeated cycles of epithelial activation/injury by some unidentified agent – Patchy interstitial fibrosis, honeycomb – Clinical – DOE and cough, hypoxemia, cyanosis, clubbing Fibrosing Diseases • Cryptogenic organizing pneumonia – Bronchiolitis obliterans organizing pneumonia – Polypoid plugs of organizing connective tissue within alveolar ducts, alveoli, bronchioles • Nonspecific Interstitial pneumonia – Cellular pattern –better prognosis – Fibrosing pattern – similar to UIP – No honeycombing Pneumoconioses • Coal Workers’ pneumoconioses – Asymptomatic anthracosis – Simple with little to no pulmonary dysfunction – Complicated – Progressive massive fibrosis – Coal macules, coal nodules, centrilobular emphysema Silicosis • Silica (silicon dioxide) – quartz most fibrogenic • The most prevalent chronic occupational disease in the world • Eggshell calcification, hard, collagenous scars • Inreased suseptibility to TB Asbestos-related DIseases • Localized fibrous plaques or rarely, diffuse pleural fibrosis • Pleural effusions • Parenchymal interstitial fibrosis (asbetosis) • Lung carcinoma • Mesotheliomas • Laryngeal and perhaps other extrapulmonary neoplasms ( e.g. colon carcinomas Complications of Therapies • Drug-induced – Table 15-7 • Radiation-induced – Radiation pneumonitis – fever, dyspnea, pleural effusion,infiltrates Granulomatous Diseases • Hypersensitivity pneumonitis – Prolonged exposure to inhaled organic agents, farmer’s lung, pigeon breeder’s lung, type IV hypersensitivity, granulomas • Sarcoidosis – Noncaseating granulomas, bilateral hilar adenopathy, eye and skin involvement, anergy, polyclonal hypergammaglobulinemia Pulmonary Eosinophilia • Acute eosinophilic pneumonia with respiratory failure • Simple pulmonary eosinophilia or Loffler syndrome • Tropical eosinophilia, caused by infection with microfilariae • Secondary eosinophilia • Idiopathic chronic eosinophilic pneumonia Smoking-related Interstitial Diseases • Smokers’ macrophages • Desquamative interstitial pneumonia • Respiratory bronchiolitis-associated interstitial lung disease Pulmonary Alveolar Proteinosis • Accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces, homogeneous granular precipitate within the alveoli • Three classes – Acquired – Congenital – Secondary Pneumoconioses • Table 15-6 - Lung diseases caused by air pollutants • Development og pneumoconiosis depends on: – Amount of dust retained in the lung and airways – Size, shape, and buoyancy of the particles most dangerous 1-5um in diameter because they may reach the terminal small airways and air sacs and settle in their linings – Possible additional effects of other irritants Disorders of Vascular Origin • Pulmonary embolism, hemorrhage and infarction • Pulmonary hypertension • Diffuse pulmonary hemorrhage syndromes – Goodpasture syndrome – Idiopathic pulmonary hemosiderosis – Wegener granulomatosis Disorders of Vascular Origin • Blood clots that occlude the large pulmonary arteries are almost always embolic in origin – 95% from deep veins in the legs • Large pulmonary embolus is one of the few causes of instantaneous death, electromechanical dissociation • Wedge-shaped infarction • Unresolved, multiple small emboli over the course of time may lead to pulmonary hypertension • Patients with a pulmonary embolus have a 39% chance of developing a second embolus Pulmonary Hypertension • Occurs when pulmonary pressure reaches ¼ systemic ( usually about 1/8) • Chronic obstructive or interstitial lung diseases • Antecedent congenital or acquired heart disease • Recurrent thromboemboli • Connective tissue disease • Obstructive sleep apnea • Idiopathic • Familial form (BMPR2 signaling pathway) • Medial hypertrophy of muscular and elastic arteries, atheromas formation, plexiform lesions Pulmonary Infections • • • • • • • • Loss or suppression of the cough reflex Injury to mucociliary apparatus Accumulation of secretions Interference with phagocytic or bactericidal action of alveolar macrophages Pulmonary congestion and edema Immunodeficiencies One type of pneumonia sometimes predisposes to another, especially in debilitated patients Many patients with chronic diseases acquire terminal pneumonias while hospitalized Pulmonary Infections • Community-acquired acute pneumonias • Community –acquired atypical (viral and mycoplasmal) pneumonias • Hospital-acquired pneumonia • Aspiration pneumonia • Lung Abscess • Chronic pneumonia • Pneumonia in the immunocompromised host – infiltrate with/without fever • Pulmonary disease in HIV infections – CD4+ counts Community Acquired Pnemonias Acute pnemonia Lobar Consolidation Bacterial Streptococcus HIB Moraxella catarrhalis S. aureus Legionella Klebsiella Pseudomonas Atypical Pneumonia Interstitial Patchy “Walking pneumonia” Mycoplasma Chlamydia Coxiella ( Q fever) Viruses Bacterial pneumnia • Lobar pneumonia – stages of inflammation fibrinosuppurative – Congestion – Red hepatization – Gray hepatization – Resolution – Complications • Abscess formation • Empyema • Bacteremic dissemination Lung Abscess • Local suppurative process within the lung, characterized by necrosis of lung tissue – central area of cavitaiton • Aspiration of infective materials • Antecedent primary lung infection • Septic embolism • Neoplasia • Miscellaneous Chronic Pneumonia • Often a localized lesion in a immunocompromised patient • Typically granulomatous • Fungal pneumonias – Resemble TB – Thermally dimorphic - hyphae, spores in environment but yeasts at body temperatures – Geographic • Histoplasmosis – Ohio and Mississippi river valleys and Caribbean • Blastomycosis – Central and southeastern US • Coccidoidomycosis – Southwest and far west US and Mexico Lung Transplantation • Indications – End-stage emphysema – Idiopathic pulmonary fibrosis – Cystic fibrosis – Idiopathic/familial pulmonary arterial hypertension • Rejection – Acute – often similar to infection, biopsy needed – Chronic – bronchiolitis obliterans – disappointing survival rate Tumors • Carcinomas • Neuroendorine proliferations and tumors carcinoid • Miscellaneous tumors – Table 15-13 Mediastinal tumors and other masses • Metastatic tumors – lung most common site of metastatic neoplasms Carcinomas • • • • Tobacco smoking Industrial hazards Air pollution Molecular genetics – c-MYC, KRAS, EGFR, c-MET, c-KIT Carcinomas • Precursor lesions – Squamous dysplasia and carcinoma in situ – Atypical adenomatous hyperplasia – Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia • Classifications – Table 15-10 – Adenocarcinoma – women, non-smokers, EGFR – Squamous cell carcinoma - smokers – Small cell carcinoma - smokers – Large cell carcinoma Carcinomas • • • • Clinical – cough, weight loss, chest pain, dyspnea, most around hilus of the lung, bronchioloalveolar – not invasive Local effects – Table 15-12 Staging – Table 15-11 Paraneoplastic – SIADH – Cushing – Hypercalcemia – Gynecomastia – Carcinoid syndrome – Lambert-Eaton myasthenic – Peripheral neuropathy – Acanthosis nigricans – Leukemoid reactions – Hypertrophic pulmonary osteoarthropathy ( clubbing) Pleura • Pleural effusions – Inflammatory pleural effusions – Noninflammatory pleural effusions • Hydrothorax • Hemothorax • Chylothorax • Pneumothorax – Emphysema, asthma, TB, spontaneous • Pleural tumors – Solitary fibrous tumor – Malignant mesothelioma