RESP-I-Obstructive_and_Restrictive_breathing-_Dec_6th-2023.pptx

OMS-1: Obstructive & Restrictive breathing: Pedro Del Corral, Ph.D. M.D. Associate Professor Department of Physiology & Pathology Burrell College of Osteopathic Medicine Dec 6th 2023 1 Objectives: Reading assignment: Robbins & Cotran (Ch 15: Obstructive lung diseases 678-688; Chronic Diffuse Int...

OMS-1: Obstructive & Restrictive breathing: Pedro Del Corral, Ph.D. M.D. Associate Professor Department of Physiology & Pathology Burrell College of Osteopathic Medicine Dec 6th 2023 1 Objectives: Reading assignment: Robbins & Cotran (Ch 15: Obstructive lung diseases 678-688; Chronic Diffuse Interstitial diseases 688-697) • Explain the pathology of emphysema and chronic bronchitis • Compare patient presentation in emphysema and chronic bronchitis • Describe the etiology of asthma • Explain the pathogenesis of asthma, differences between atopic and non atopic asthma • List the characteristics of chronic interstitial pulmonary diseases • Differentiate among the pneumoconiosis • Explain the pathogenesis & morphology of pulmonary idiopathic fibrosis 2 Obstructive pulmonary diseases • Characterized by an increase in resistance to flow due to partial/complete obstruction at any level • From Trachea  respiratory bronchioles • It affects nearly 10% of the population in the USA • 4th leading cause of death • Obstructive pulmonary diseases • • • • Emphysema Chronic bronchitis Asthma Bronchiectasis • Chronic obstructive pulmonary disease • Emphysema • Chronic bronchitis diseases 3 Schematic representation of the overlap in obstructive pulmonary diseases • 80% of COPD due to smoking • 35-50% of heavy smokers develop COPD • Other risk factors: • Occupational pollutants • Airway hype-responsiveness • Genetic polymorphism Emphysema 4 Obstructive pulmonary diseases: Emphysema • Characterized by irreversible enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their wall without obvious fibrosis AKA - Panlobular • Etiology • Behavioral • Genetic • Anatomical classification • • • • Centriacinar Panacinar Paraseptal Irregular 5 COPD: Emphysema • Pathology: Loss of alveolar walls & parts of the capillary bed • ↓ surface area for gas exchange • Inflx response, PMNL damage • Bronchus compression: loss of radial traction of alveolar walls and consequent narrowing. • Loss of elastic tissue from alveolar walls • Lung expansion • Compression of small airways • Resistance • expiration 6 COPD: Clinical course of emphysema • Symptomatic Presentation – at least 1/3 lung parenchyma is damaged • Signs & Symptoms: Dyspnea, weight loss, barrel-chested, breathes through pursed lips, prolonged expiration, wheezing, cough • DX: ↓FEV1/FVC • Complications: Respiratory failure, Cor Pulmonale • Treatments: beta adrenergic agents, glucocorticoids, and α1-antitrypsin replacement (when applicable), missing? COPD: Chronic bronchitis 7 COPD: Chronic bronchitis • Clinical definition: Excessive mucous production in bronchial tree, on most days for at least 3 months in 2 successive years in the absence of any other identifiable cause • Etiology: • Cigarette smoking (90%) • Inhabitants of smug (sulfur dioxide, nitrogen dioxide) laden cities 8 COPD: Pathogenesis of Chronic bronchitis • Pathogenesis • A. Partial lumen occlusion: excessive mucous secretions. • Protective response against tobacco & toxic gases • Hypertrophy Submucosal glands in trachea & bronchi • Earliest feature • B. Inflammation • Acute, Chronic • ↑ airway wall thickness, ↓ luminal diameter, ↑fibrosis • ↓Ciliary function  Infection: • Plays a key role in maintaining chronic bronchitis 9 Chronic Bronchitis • Patient presentation • ↑ dyspnea • Frequent cough and sputum • Substantial drop in PaO2 1. Inflammatory reaction 2. Mucous Plug 3. Mucous Cell Hyperplasia • ↑↑PaCO2 • Tend to be overweight • DX: ↓FEV1/FVC • Treatment • Behavior change • Beta agonist, glucocorticosteroids • Antibiotics • O2 therapy 4. Smooth Muscle Hypertrophy • Complications • Cor pulmonale Asthma 10 Obstructive pulmonary diseases: Asthma is a disorder of the conducting airways usually caused by an immunological reaction which is marked by episodic bronchoconstriction • Etiology: (triggers) • Respiratory infections, exposure to irritants • Cold air, exercise, stress • Bronchoconstriction is due to: • ↑ airway sensitivity to a variety of stimuli • inflammation of bronchial walls • an ↑ mucous secretion • Pathology shows: • B. Inside the wall of the airway: hypertrophy of smooth muscle, glandular hypertrophy, inflammation edema • Classification of Asthma according to: • Allergen sensitization, immune reaction • Yes - Atopic • No - Non Atopic • Also • Drug-induced • Occupational 11 Obstructive pulmonary diseases: Types of Asthma • 1. Atopic • IgE type hypersensitivity (Type-I) • Most common • Triggered by allergens such as • Dust, pollen, cockroach, foods, animal dander – most often in synergy with viral infection • Family history • Dx: Skin test  wheal & flare reaction • Dx: Eosinophilia, ↑ IgE levels • 2. Non-Atopic • Infections (rhinovirus, RSV, parainfluenza) • ↓ Threshold for epithelial vagal receptors • Triggers: • Smoking & air pollutants, cold & exercise • Some family history, not as prevalent as in atopic asthma • Dx: Skin test is negative, no ↑ serum IgE 12 Obstructive pulmonary diseases: Types of Asthma-----------------Clinical course • 3. Drug Induced (Aspirin) • Individuals with rhinitis, & nasal polyps • Affects ~ 10% of patients with asthma • Inhibits cyclooxygenase pathway • Presents: wheezing, coughing, anxiety • Usually at night or early morning • Attacks can last several hours • Up to 50% childhood asthma goes away • Diagnosis by spirometry • 4. Occupational Asthma • Fumes (epoxy resins, plastics), organic & chemical dusts (wood, cotton) • Toluene, formaldehyde • ↓ FEV1/FVC • Reversibility by bronchodilators • Treatment • Avoid known allergens • Beta adrenergic agents • Glucocorticoids Restrictive diseases 13 Chronic interstitial pulmonary diseases characterized predominantly by inflammation and fibrosis of the pulmonary inter­stitium • Bilateral lesions that take the form of small nodules, irregular lines, or ground-glass shadows, all corresponding to areas of interstitial fibrosis (seen in CXR) • The classic functional abnormalities are reductions in diffusion capacity, lung volume, and lung compliance. • PFTs = restrictive lung disease. • FEV1/FVC = is normal range (both decreased) • Although the entities can often be distinguished in the early stages, the advanced forms are hard to differentiate because all result in scarring and gross destruction of the lung, often referred to as endstage lung or honeycomb lung. • Complications: secondary pulmonary hypertension and right-sided heart failure associated with cor pulmonale may result. 14 Idiopathic Pulmonary Fibrosis is marked by progressive interstitial pulmonary fibrosis and respiratory failure. • AKA - Usual interstitial pneumonia, Cryptogenic fibrosing alveolitis. • Etiology: unknown • Pathogenesis: It appears, genetically prone to aberrant repair of recurrent epithelial cell injury caused by environmental factors • TGF-β • Pro-fibrogenic factor • Morphology: • • • • Earliest lesions -fibroblastic foci Initially subpleural patches Eventually diffuse fibrosis Cystic spaces • Honeycomb lung Figure 15.13 Pathogenic mechanisms of idiopathic pulmonary fibrosis 15 Idiopathic Pulmonary Fibrosis • Presentation: above 50 y of age, dyspnea on exertion, progressive dyspnea, & dry cough • Diagnosis: • CT • Biopsy • Treatment: • immunosuppression • lung transplant Figure 15-14 Usual interstitial pneumonia. The fibrosis is more pronounced in the subpleural region. Pneumoconioses 16 Pneumoconioses are non-neoplastic lung reactions induced by organic and inorganic particulates and chemical fumes and vapors • Pathogenesis depends on: • • • • Amount of dust retained Size (1-5 μm), shape, and buoyancy of the particles Particle solubility and physiochemical reactivity Possible additional effects of other irritants (e.g., cigarette smoke) • Pneumoconiosis (we will focus on 3 entities) • 1. Coal workers’ Pneumoconiosis • Lung disease caused by inhalation of coal particles & other admixed forms of dust • Pathology: • Anthracosis: most innocuous form, carbon pigment is engulfed by alveolar or interstitial macrophages, accumulating in connective tissue • Coal macules (1-2 mm) • Coal nodules: larger, + collagen 17 Pneumoconioses: Coal workers’ Pneumoconiosis Black lung • Pathology • Complicated Coal workers’ pneumoconiosis (i.e., progressive massive pneumoconiosis) • Multiples lesion, intense black scars 1-10 cm diameter • Coal nodules, + necrosis • Patient: coal miner • mild or • severe (progressive massive pneumoconiosis) • Pulmonary-HTN • RHF Silicosis 18 Pneumoconiosis: Silicosis, caused by inhalation of proinflammatory crystalline silicon dioxide • Pathology • 1. Silica phagocytosed by macrophages • 2. Activation of Inflammation (IL-1 & IL-18 • 3. In hilar lymph nodes & upper lung, see nodular fibrosing • 4. coaslesce hard collagenous scars • Progression  central area of whorled collagen fibers • • Complications: • ↑Risk for TB & lung CA • Patients: sandblaster, silica miners, repair/demolition concrete structures • Present asymptomatic/mild decreases in PFT, except in progressive massive fibrosis Figure 15-19 Several coalescent collagenous silicotic nodules Asbestosis 19 Asbestos is a family of proinflammatory crystalline hydrated silicates associated with pulmonary fibrosis, carcinoma, mesothelioma and other cancers • Pathogenesis of asbestosis • Depends on form of asbestos • Serpentine chrysotile: 90% of cases • Amphibole: more likely to cause mesothelioma • Once phagocytosed by macrophages, asbestos fibers activate the inflammasome • Macrophages attempt to clear the fibers • Morphology: • Diffuse pulmonary interstitial fibrosis + asbestos bodies (golden brown, fusiform, or beaded rods with iron containing material) • Fibrosis around respiratory bronchioles advancing distally • Pleural plaques of collagen • Presentation of asbestosis • Mining, milling, insulation workers, plumbers, shipyard workers • Usually after 20-30 y of exposure • Dyspnea on exertion  dyspnea at rest Figure. 15-20. High Power detail of an asbestos body, revealing the typical beading and knobbed ends Sarcoidosis 20 Sarcoidosis is a systemic granulomatous disease of unknown origin • Etiology: unknown, but may be due to disrupted immune regulation CD4-T cell response to antigen • Localized immune abnormalities • Aberrant expansion of CD4+ T cells, consistent with antigen-driven response • ↑ TH1 cytokines (IL-2 and IFN-γ) • ↑ local production of TNF-α (and other cytokines) promotes granuloma formation • Target organs: Can affect nearly every organ in the body, 90% of cases have bilateral hilar lymphadenopathy or lung involvement; skin (erythema nodosum); uveitis • Systemic Immunologic abnormalities • Anergy to skin tests (candida or PPD) 21 Sarcoidosis • Pathology: Involved tissues contain noncaseating granulomas • Aggregates of clustered epithelioid macrophages • See Asteroid bodies • Hilar lymph nodes & lungs • Clinical features • Usually occurs in adults <40 yo, African Americans (10 x vs Caucasians), females • Dyspnea, cough, hemoptysis, fatigue, lymphadenopathy • Erythema nodosum, uveitis • Treatment: glucocorticoids, resolves spontaneously in 2/3 of cases Figure 15-22 Bronchus with characteristic noncaseating sarcoidal granulomas (asterisks), with many multinucleated giant cells (arrowheads). Note subepithelial location of granulomas. 22