Obstructive and Restrictive Lung Diseases PDF

8/25/2024 OBSTRUCTIVE Vs RESTRICTIVE PULMONARY DISEASES BY: Dr. Addisu A. Basic concepts Ventilation/ Perfusion (V /Q) mismatch – airspace inadeq...

8/25/2024 OBSTRUCTIVE Vs RESTRICTIVE PULMONARY DISEASES BY: Dr. Addisu A. Basic concepts Ventilation/ Perfusion (V /Q) mismatch – airspace inadequately perfused or perfused areas inadequately ventilated – Either way the outcome is hypoxia Improves with O2 administration – Examples COPD (e.g. Asthma…) Interstitial lung disease, and pulmonary vascular disease 1  8/25/2024 Basic concepts … Right-to-left (R-to-L) shunting – Perfusion of non-ventilated alveoli – Do NOT improves with O2 administration – Examples ARDS, intra-alveolar filling (pneumonia, pulmonary edema) Mechanical Ventilator Basic concepts… Decreased diffusion – Marked thickening of the alveolar-capillary interface – The diffusing capacity of the lungs for carbon monoxide (DLCO or DLCO) test measures how well inspired CO diffuses from the alveoli to RBC hemoglobin – Examples interstitial lung diseases (ILDs) and emphysema – Improves with O2 administration 2  8/25/2024 Generally oxygen transported to the tissues depends on 3 factors: A. Cardiac output B. Hemoglobin level C. Hemoglobin saturation (SO2) Pulse oximeter Problem based learning (PBL) Case presentation 3  8/25/2024 Introduction Pulmonary function test 4  8/25/2024 Forced vital capacity (FVC): total volume of air expelled after a maximal inspiration. Normal FVC is 5 L Forced expiratory volume in 1 second (FEV1): amount of air expelled from the lungs in 1 second after a maximal inspiration. Normal FEV1 is 4 L Ratio of FEV1/FVC is normally 4/5, or 80% Obstructive disease (airway disease) characterized by an increase in resistance to air flow caused by partial or complete obstruction at any level – reduction of pulmonary air flow – normal or increased total lung capacity (TLC) – forced vital capacity (FVC) is either normal or slightly decreased, The major diffuse obstructive disorders - Emphysema chronic obstructive - Chronic bronchitis pulmonary disease (COPD) - Bronchiectasis - Asthma 10 5  8/25/2024 decreased expiratory flow rate, usually measured by forced expiratory volume at 1 second (FEV1) ↓↓ FEV ↑↑ dyspnea COPD 6  8/25/2024 Restrictive disease Characterized by reduced expansion of lung parenchyma, with decreased total lung capacity. – FVC is reduced and the expiratory flow rate is normal – Reduced compliance Restrictive diseases occur in - Chest disorders – kyphoscoliosis, polio, obesity, pleural disease, GBS - Acute or chronic interstitial & infiltrative diseases ARDS, pneumoconioses, interstitial fibrosis 14 7  8/25/2024 Time (sec) 0 1 2 3 4 1 2 Vol R (L) 3 4 FEV1sec N 5 FVC 6 8  8/25/2024 Quiz What is FEV1sec/FVC of normal (N) and obstructive (O) curves from the previous diagram? What lung volumes can NOT be measured in spirometer? What is the most reliable spirometric measurement that is informative to differentiate between obstructive and restrictive lung disease? What keeps the distal (beyond Bronchioles) airways open? Emphysema Is characterized by permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls & without obvious fibrosis defined on the basis of morphologic and radiologic features 18 9  8/25/2024 Types of emphysema According to its anatomic distribution the major types are 1. Centriacinar 2. Panacinar 3. Paraseptal 4. Irregular 19 Types of emphysema… 1.Centriacinar /Centrilobular/ – The most common type – central or proximal parts of the acini, formed by respiratory bronchioles, are affected, while distal airway spared – More common and severe in the upper lobes particularly in the apical segments – most common in cigarette smokers 20 10  8/25/2024 Types of emphysema… 2.Panacinar – Acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli – Lower lobes > upper – Associated with α1-anti-trypsin deficiency 21 Types of emphysema … 3. Distal Acinar (paraseptal) Emphysema The proximal portion of the acinus is normal, but the distal part is predominantly involved. More striking adjacent to the pleura along the lobular connective tissue septa Occurs adjacent to areas of fibrosis, scarring or atelectasis More severe in the upper half of the lungs Sometimes form cyst like structures (Bullae) Underlies many of the spontaneous pneumothorax 22 11  8/25/2024 Types of emphysema … 4. Airspace enlargement with fibrosis ( Irregular Emphysema) The acinus is irregularly involved Almost invariably associated with scarring Asymptomatic & clinically insignificant 24 12  8/25/2024 Pathogenesis 25 Pathogenesis… Inflammatory cells and mediators: – inflammatory mediators have been shown to be increased (chemotactic factors, proinflammatory cytokine) – neutrophils, macrophages, and CD4+ and CD8+ T cells. The protease – antiprotease imbalance – Several proteases are released from the inflammatory cells and epithelial cells – relative deficiency of protective anti-proteases 26 13  8/25/2024 Pathogenesis… Oxidative stress: – ROS generated by cigarette smoke and other inhaled particles and released from activated inflammatory cells such as macrophages and neutrophils. → additional tissue damage and inflammation Airway infection: – cause acute exacerbations 27 Pathogenesis… α1-Antitrypsin (which is synthesized in liver), normally present in serum, tissue fluids, and macrophages, is a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation Protease-mediated damage of extracellular matrix has a central role in the airway obstruction seen in emphysema 14  8/25/2024 Pathogenesis… Normally, the lung contains a healthy complement of antioxidants (superoxide dismutase, glutathione) that keep oxidative damage to a minimum. Tobacco smoke contains abundant reactive oxygen species (free radicals), which deplete these antioxidant mechanisms, thereby inciting tissue damage. 29 30 15  8/25/2024 Morphology - Diagnosis and classification of emphysema is mainly on macroscopic appearance - Panacinar emphysema, produces pale, voluminous lungs that often obscure the heart - The macroscopic features of centriacinar emphysema are less impressive - the upper two thirds of the lungs is more severely affected 31 32 16  8/25/2024 33 Histologically, – thinning and destruction of alveolar walls. – With advanced disease, adjacent alveoli become confluent, creating large airspaces 34 17  8/25/2024 Medial hypertrophy of small arteries and arterioles is a characteristic feature of pulmonary hypertension 35 Clinical course – Do not appear until one third of pulmonary parenchyma is damaged – Dyspnea – Weight loss – Expiratory airflow limitation by spirometry – Emphysema patients- pink puffers – Chronic bronchitis- blue bloaters – Development of cor-pulmonale and congestive heart failure secondary to pulmonary hypertension – Massive collapse of lungs secondary to pneumothorax 36 18  8/25/2024 Stereotypical pictures of COPD patients 31 Pink Puffer Blue Bloater Chronic bronchitis defined on the basis of clinical features Defined as persistent cough with sputum production for at least 3 months in at least 2 consecutive yrs, in the absence of any other identifiable cause Common in smokers & inhabitants of smog ridden cities – Some have evidence of hyperresponsive airways, initially involves the large airway 38 19  8/25/2024 Pathogenesis The distinctive feature is hypersecretion of mucus, beginning in the large airways Chronic irritation by inhaled substances; smoking in 90% – hypertrophy of mucous glands in the trachea and bronchi as well as an increase in mucin-secreting goblet cells in the epithelial surfaces of smaller bronchi and bronchioles. – cause inflammation marked by the infiltration of macrophages, neutrophils, and lymphocytes 39 Pathogenesis … the airflow obstruction in chronic bronchitis results from – small airway disease, induced by mucous plugging of the bronchiolar lumen, inflammation, and bronchiolar wall fibrosis, – coexistent emphysema. 40 20  8/25/2024 Morphology Hyperemia, swelling, edema of mucus membranes accompanied by excessive secretion Chronic inflammation of the airways, & enlargement of mucus secreting glands Reid index (normally 0.4) is increased – Reid index ratio of the thickness of the mucus gland layer to the thickness of the wall between the epithelium & the cartilage Marked narrowing of bronchioles – In severe cases, bronchiolitis obliterans 42 21  8/25/2024 43 Clinical features quite variable presentation Persistent productive cough Dyspnea Cor pulmonale with cardiac failure Differentiation of this form of COPD from that caused by emphysema can be made in the classic case, but many patients have both conditions 44 22  8/25/2024 Asthma It is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or in the early morning The hallmarks of asthma are intermittent, reversible airway obstruction; increased in incidence significantly in the Western world –hygiene hypothesis 46 23  8/25/2024 Classification 1. depending on the frequency & severity of symptoms – Mild – Moderate – Severe 2. inciting agent – Extrinsic (atopic) – Intrinsic (non atopic) 47 Pathogenesis genetic predisposition to type I hypersensitivity (atopy), acute and chronic airway inflammation, and bronchial hyperresponsiveness to a variety of stimuli Initial sensitization to inhaled antigens which stimulate induction of TH2 type cells that release cytokines These cytokines promote IgE production by B cells, growth of mast cells, & activation of eosinophils Sub epithelial vagal (parasymphatetic) stimulation provokes broncho constriction 48 24  8/25/2024 Pathogenesis… Subsequent IgE mediated reaction to inhaled allergens elicits a mast cell derived mediators released in two phases – An early phase reaction: beginning 30 to 60 minutes after inhalation of antigen Triggered by preformed mediators form from mast cells granules dominated by bronchoconstriction, increased mucus production, and vasodilation 49 Pathogenesis… – late phase. 4 to 8 hours later and more protracted is inflammatory in nature Inflammatory mediators form resident immune cells → recruitment of TH2 cells, eosinophils, and other leukocytes, thus amplifying an inflammatory reaction 50 25  8/25/2024 51 Atopic Asthma Usually begins in childhood Triggered by environmental pollutants Positive family history is common Asthmatic attacks often preceded by allergic rhinitis, urticaria or eczema Skin test is positive to allergen injection 52 26  8/25/2024 Non-Atopic Asthma Most frequently triggered by viral respiratory infection Positive family history is uncommon Serum IgE level is normal, Skin test is negative No associated allergens Virus induced inflammation of the respiratory mucosa lowers the threshold of the sub epithelial vagal receptors to irritants Inhaled air pollutant may also contribute 53 Other forms Drug induced Asthma Asprin – tipping the balance toward bronco constrictor leukotrines (arachidonic acid leukoterin Occupational asthma Fumes, dusts 54 27  8/25/2024 Morphology Occlusion of bronchi and bronchioles 55 mucus plug containing whorls of shed epithelium (Curschmann spirals) 28  8/25/2024 Morphology… Numerous eosinophils and Charcot-Leyden crystals (crystalloids made up of the eosinophil protein galectin- 10) also are present. 57 Airway remodeling: characteristic finding of asthma – Thickening of airway wall – Sub-basement membrane fibrosis – Increased submucosal vascularity – An increase in size of the submucosal glands and goblet cell metaplasia of the airway epithelium – Hypertrophy and/or hyperplasia of the bronchial muscle 58 29  8/25/2024 Clinical course severe dyspnea and wheezing due to bronchoconstriction and mucus plugging, which leads to trapping of air in distal airspaces and progressive hyperinflation of the lungs. Acute exacerbation of asthma Status asthmaticus (a severe paroxysm that does not respond to therapy and persists for days and even weeks) 59 Bronchiectasis permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue resulting from or associated with chronic necrotizing infection manifested by cough, fever, & copious amounts of foul smelling position dependent, purulent sputum 60 30  8/25/2024 61 Bronchiectasis… Bronchiectasis is not a primary disorder; it develops in association with: Bronchial obstruction – – tumors, foreign bodies, impaction of mucus Congenital or hereditary conditions – – cystic fibrosis, intralobular sequestration of lung – Primary ciliary dyskinesia (aka the immotile cilia syndrome Necrotizing, or suppurative, pneumonia – – immunodeficiency state, – Staphylococcus aureus or Klebsiella spp. Posttuberculosis 62 31  8/25/2024 PATHOGENESIS Two intertwined processes contribute to bronchiectasis: obstruction and chronic infection. – Either may be the initiator Pooling of secretions distal to obstruction → superimposed infection → inflammatory damage to the bronchial wall and the accumulating exudate Severe infections of the airway lead to inflammation, often with necrosis, fibrosis, and eventually dilation of the airways In primary ciliary dyskinesia poorly functioning cillia contribute to the retention of secretions & recurrent infection that in turn gives brochiectasis 63 Morphology Usually affects the lower lobes (passages that are most vertical) The distal airways are dilated – more severe in distal bronchi and bronchioles → cyst like dilataion filled mucopurulent secretions – may extend to near the periphery (plural surface) of the lung 64 32  8/25/2024 Morphology… Intense acute and chronic inflammatory exudate within the walls of the bronchi and bronchioles Healing – ? regeneration vs repair Production of an abscess cavity 65 Clinical course Diagnosis depends on an appropriate history and radiographic demonstration of bronchial dilation. severe, persistent cough associated with expectoration of mucopurulent, sometimes expectoration of foul smelling, hemoptysis 66 33  8/25/2024 Complications Cor pulmonale Metastatic brain abscess amyloidosis 67 34  8/25/2024 CHRONIC DIFFUSE INTERSTITIAL (RESTRICTIVE, INFILTRATIVE) LUNG DISEASES (1)chronic interstitial and infiltrative diseases (2)chest wall disorders (e.g., neuromuscular diseases such as poliomyelitis, severe obesity, pleural diseases, and kyphoscoliosis) 70 35  8/25/2024 Chronic interstitial (restrictive) lung diseases Chronic interstitial diseases are a heterogeneous group of disorders characterized by bilateral, often patchy, pulmonary fibrosis mainly affecting the walls of the alveoli categorized based on clinicopathologic features – PFT changes are those of restrictive lung disease – there is frequent overlap in histologic features 71 The hallmark of these disorders is – reduced compliance (i.e., more pressure is required to expand the lungs), → increased effort of breathing (dyspnea). – Abnormalities in the ventilation–perfusion ratio, leading to hypoxia. 72 36  8/25/2024 Pts have dyspnea, tachypnea & resp. crackles, cyanosis with out wheezing or other evidence of airway obstruction CXR shows diffuse infiltration by small nodules, irregular lines or ground glass shadows Eventually, pulmonary HTN & right sided heart failure with cor pulmonale may result they all result in diffuse scarring and gross destruction of the lung, referred to as end-stage or “honeycomb” lung. 73 37 8/25/2024 38  8/25/2024 Pneumoconiosis Lung disorders caused by inhalation of mineral dusts, organic particulates, chemical fumes & vapors Agent Disease Exposure Coal dust Simple coal worker’s pneumoconiosis: Coal mining macules and nodules Complicated coal worker’s pneumoconiosis: PMF Silica Silicosis Sandblasting, quarrying, mining, stone cutting, foundry work, ceramics Asbestos Asbestosis, pleural effusions, pleural Mining, milling, and fabrication of plaques, or diffuse fibrosis; ores and materials; installation and mesothelioma; carcinoma of the lung removal of insulation 77 and larynx Pneumoconiosis… Pathogenesis Particles that are 1 to 5 μm get lodged at the bifurcation of the distal airways. Coal dust is relatively inert, and large amounts must be deposited in the lungs Silica and asbestos are more reactive than coal dust, resulting in fibrotic reactions at lower concentrations. The pulmonary alveolar macrophage is a key cellular element in the initiation and perpetuation of inflammation, lung injury and fibrosis Tobacco smoking worsens the effects of all inhaled mineral dusts, more so with asbestos than other particles 78 39  8/25/2024 1. Coal workers’ pneumoconiosis Lung findings range from – Asymptomatic anthracosis – Simple coal workers pneumoconioses Macrophages accumulate with little to no pulmonary dysfunction – Progressive massive fibrosis (complicated CWP) intensely blackened scars larger than 2 cm confluent fibrosing reaction in the lung lung function is compromised Caplan syndrome – coexistence of rhematoid arthritis with pnemoconioses 79 Morphology Anthracosis – innocuous, coal induced pulmonary lesion, commonly seen in all urban dwellers & tobacco smokers & the inhaled carbon accumulate in CT. Simple CWP – coal macules containing carbon laden macrophages 1-2mm in diameter, coal nodules, upper lobe heavily involved Complicated CWP – generally requires many years to develop , intense black scars, dense collagen & pigment with areas of necrosis 80 40  8/25/2024 Anthracotic pigment 81 Clinical course CWP is benign disease with little decrement in lung function. < 10% develop PMF leading to pulmonary dysfunction, pulmonary HTN & cor pulmonale once established PMF has a tendency to progress even in the absence of further exposure. Increased risk of chronic bronchitis & emphysema CWP doesn’t predispose to cancer independent of smoking 82 41  8/25/2024 2. Silicosis Caused by inhalation of crystalline silicon dioxide (silica) Exposure: sand blasting, hard rock mining, stone cutting After inhalation the particles will interact with epithelial cells & macrophages (release mediators) Some of the cytokines include IL-1, TNF, fibronectin, lipid mediators, oxygen derived free radical & fibrogenic cytokines 83 Morphology Silicotic nodules in their early stages are tiny, barely palpable, discrete, pale- to-black (if coal dust is present) nodules in the upper zones of the lungs concentrically arranged hyalinized collagen fibers surrounding an amorphous center CXR egg shell calcification Examination by polarized microscopy birefrigent silica particles 84 42  8/25/2024 Clinical feature Most prevalent chronic occupational disease in the world Occurs after decades of exposure & cause nodular fibrosing pneumoconiosis Most pts do not develop dyspnea until late in the course It increases susceptibility to TB – depression of cell-mediated immunity, – Inhibition of the ability of pulmonary macrophages to kill phagocytosed mycobacteria Its relation with cancer is controversial 85 3. Asbestosis related disease Asbestos is a family of crystalline hydrated silicates that form fibers Its exposure is linked to Pleural effusion or fibrosis parenchymal interstitial fibrosis Lung cancer (5x) Mesothelioma Laryngeal or colonic cancer It causes diffuse interstitial disease unlike silicosis which causes nodular fibrosing disease Asbestosis can act as tumor initiator or promoter 86 43  8/25/2024 Morphology It is difficult to differentiate from other diffuse interstitial disease unless there is asbestos bodies – a beaded or dumbbell-shaped rod with a central clear core and golden brown coating; it may be straight or curved Fibrosis begins around the bronchioles & alveolar ducts Unlike other forms of pneumoconiosis it affects the lower lobes Pleural plaques are the most common manifestations of asbestosis May be complicated by pulmonary HTN & cor pulmonale 87 asbestos (ferruginous bodies) 88 44  8/25/2024 Clinical features similar to those caused by other diffuse interstitial lung diseases Pleural plaques are usually asymptomatic and are detected on radiographs as circumscribed densities 89 Idiopathic pulmonary fibrosis Also called cryptogenic fibrosing alveolitis It refers to a clinicopathologic syndrome with a characteristic radiologic, pathologic & clinical features Histological features of usual interstitial pneumonia is required for its diagnosis 90 45  8/25/2024 Pathogenesis Unknown etiology It is caused by repeated cycles of acute lung injury (alveolitis) by some undefined agents The inflammatory response is mediated by TH2 cell types Wound healing at these sites give rise to exuberant fibrosis Genetic & environmental factors modify the phenomenon 91 Morphology Pleural surface grossly cobblestoned owing to retraction of scars along the interlobular septa Microscopically the hallmark UIP is patchy interstitial fibrosis & the earliest manifestation is fibroblastic foci 92 46  8/25/2024 Clinical course Age 40-70 yrs ( >60yrs ) Dyspnea Dry cough Hypoxemia Cyanosis Clubbing Mean survival is 3 yrs Lung transplantation is the only definitive therapy 93 Non specific interstitial pneumonia Etiology unknown Lung biopsies failed to show diagnostic feature of any of the DILD, a "wastebasket" type of diagnosis Better prognosis than UIP (usual interstitial pneumonia) Morphologically, it has cellular & fibrosing patterns Cellular components include chronic inflammatory cells, has good out come Diffuse & patchy fibrosis Younger than UIP 94 47  8/25/2024 Granulomatous Diseases Sarcoidosis a multisystem disease of unknown etiology characterized by noncaseating granulomas in many tissues and organs bilateral hilar lymphadenopathy or lung involvement (or both), visible on chest radiographs, is the major presenting manifestation in most cases. Eye and skin involvement each occurs in about 25% of cases and may occasionally be the presenting feature of the disease 95 48  8/25/2024 Epidemiology A consistent predilection for adults younger than 40 years of age. A high incidence in Danish and Swedish populations, and in the United States among African Americans A higher prevalence among nonsmokers, an association that is virtually unique to sarcoidosis among pulmonary diseases 97 Etiology and Pathogenesis Unknown etiology, disorder of immune regulation in genetically predisposed individuals exposed to certain environmental agents. development of a cell-mediated response to an unidentifed antigen Several putative antigen have been proposed viruses, mycobacteria, Borrelia, pollen 49  8/25/2024 Morphology: predominantly involve airway submucosa and the pulmonary interstitium rather than airspaces regardless of the organ involved Non caseating epitheloid granuloma Asteroid bodies(inclusions in multinucleated giant cells) Schaumann bodies: laminated concretions composed of calcium and proteins 99 100 50  8/25/2024 101 Clinical Course - In many individuals the disease is entirely asymptomatic - In about two-thirds of symptomatic cases there is a gradual appearance of respiratory symptoms (shortness of breath, dry cough, or vague substernal discomfort) or constitutional signs and symptoms (fever, fatigue, weight loss, anorexia, night sweats). 102 51  8/25/2024 Hypersensitivity pneumonitis Immunologically mediated disorder affecting airways and interstitium. is an immunologically mediated response to an extrinsic antigen that involves both immune-complex and delayed- type hypersensitivity reactions Most often it is an occupational disease that results from heightened sensitivity to inhaled antigens such as moldy hay. 103 Unlike bronchial asthma, in which bronchi are the focus of immunologically mediated injury, the damage in hypersensitivity pneumonitis occurs at the level of alveoli. Hence, it presents as a predominantly restrictive lung disease with decreased diffusion capacity, lung compliance, and total lung volume. 104 52  8/25/2024 Thank You!!! 53