500 likes | 523 Views
Pathophysiology of asthma and chronic obstructive pulmonary disease. M. Tatár. OBSTRUCTIVE LUNG DISEASES. localized: laryngeal constriction, tracheal and bronchial carcinoma, foreign bodies. generalized: asthma, COPD, bronchiectasis, cystic fibrosis.
E N D
Pathophysiology of asthmaand chronic obstructive pulmonary disease M. Tatár
OBSTRUCTIVE LUNG DISEASES localized: laryngeal constriction, tracheal and bronchial carcinoma, foreign bodies generalized: asthma, COPD, bronchiectasis, cystic fibrosis OBSTRUCTIVE VENTILATORY DISORDER - spirometry Airflow limitation
End of quiet expiration - 0.5 - 2.5 0.5 Inspiration 0 0 0 0 0
Inspiration - 2.5 + 2.0 Forced expiration 0.5 - 2.0 - 1.5 - 1.0 - 0.5 0
Forced expiration + 2.0 0.5 + 2.5 + 1.0 0 + 2.0 + 1.5 EPP
ASTHMA - definition Chronic inflammatory disorder of the airways Mast cells, eosinophils, T-lymphocytes Recurrent episodes of wheezing, dyspnoea, and cough particularly at night and early morning Symptoms are associated with airflow limitation that is partly reversible either spontaneously or with therapy Bronchial hyperresponsiveness is present very often
Volume Normal subject Asthmatic (after bronchodilator) Asthmatic (before bronchodilator) FEV1 1 2 3 4 5 Time (seconds)
ASTHMA - classification A. Intrinsic asthma • no environmental causes can be identified • negative skin test to common airborn allergens • rather negative family history B. Extrinsic asthma • atopy, genetic predisposition • IgE, mast cells and eosinophils response to allergens C. Occupational asthma • sensibilisation of airways to inhalant chemicals
Development of asthma Risk factors Predisposing: atopy, gender Causal: allergens, aspirin, chemicals Contributing: respiratory infections, diet, air pollution, smoking Factors that exacerbate asthma - triggers allergens, respiratory infections, exercise, emotions
Triggers Respiratory infections • epithelial damage • airway inflammation Exercise reflex airflow limitation • cooling of mucosa • osmolarity changes of fluid lining epithelium Emotions (laughing, crying, anger, fear) • hyperventilation • hypocapnia
Asthma - bronchial hyperresponsiveness Instability of the airways = exaggerated bronchoconstrictor response to a wide variety of stimuli Key factor - airway inflammation Mechanisms: direct and indirect
Airway hyperresponsiveness Direct agonists e.g. methacholine Nerve Airway with limited airflow Mediators SO2, bradykinin Indirect agonists e.g. exercise, adenosine, hypotonic or hypertonic aerosols Mast cell
antihyperreactiv factors prohyperreactiv factors 2-adrenergic -adrenergic VIP/PHM cholinergic anticholinergic im balance SP/NK NEP oxygen-free radicals antioxidants peptidases corticoids Airway hyperresponsiveness Normal airway reactivity
Pathological changes in chronic asthma Airway wall remodeling Normal airway Epithelium Basement membrane Smooth muscle Mucus plug Mucus glands
Mechanisms of asthma 1. Airway inflammation - recruitments of inflammatory cells from circulation - endothelial adhesion molecules - activation of T lymphocytes (Th2 clone) - production of IgE, leukotriens, prostanoids - cytokines (CD4+ Th subtype) 2. Neural control of airways
Neurogenic inflammation Antigen etc. Macrophage Mast cell T-lymphocyte Neutrophil Eosinophil Mucus plug Epithelial shedding Vasodilation Subepithelial fibrosis Sensory nerve Plasma leak Efferent nerve Oedema Airway constriction and smooth muscle hypertrophy/hyperplasia
Asthma - airflow limitation 1. Acute bronchoconstriction 2. Swelling of the airway wall 3. Chronic mucus plug formation 4. Airway wall remodeling
Relaxation Constriction muscle constriction 35 % Airway narrowing Normal R = 10 R = 1 muscle constriction 35 % Exaggerated airway narrowing Asthma R = 2 R = 40
INFLAMMATION Risk factors (for development of asthma) Airway hyperresponsiveness Airflow limitation Symptoms Risk factors (for exacerbations)
Asthma is a highly variable disease Asthma is a chronic inflammatory disease of variable severity. Worsening and exacerbations of asthma are associated with episodes of acute inflammation, which develop on top of persistent underlying chronic inflammation. This acute inflammation causes an increase in symptoms and may also lead to an increased sensitivity to triggers and a worsening in airway hyperresponsiveness. The variability and severity of „real life“ asthma is dependent on a number of factors, including a patient´s adherence to the prescribed treatment.
COPD - definition Chronic airflow limitation ( maximum expiratory flow, slow forced emptying of the lungs) Airflow limitation is slowly progressive and irreversible • Due to varying combinations of: • airway disease • emphysema
Chronic bronchitis defined in clinical terms chronic cough with sputum production - (3 months a year, 2 successive years) - excluded cardiac or other pulmonary causes Emphysema defined anatomically permanent, destructive enlagrement of airspaces distal to the terminal bronchioles without obvious fibrosis COPD
COPD - risk factors Cigarette smoking 1 - antitrypsin deficiency Solid fuel used for indoor heating or cooking without adequate ventilation Heavily polluted environments
100 Never smoked 75 Smoked regularly Stopped at age 45 yrs FEV1 % 50 Disability 25 Stopped at age 65 yrs Death 0 75 25 50 Age yrs
COPD - cellular and biochemical mechanisms Inflammation: alveolar macrophages, neutrophils production of elastase, cathepsine G, collagenase oxidative stress in smokers and in COPD patients Neutrophil and macrophage enzymes and oxidants destroy components of extracellular matrix (collagen, elastin, fibronectine, proteoglycans) Loss of cellular components of lung parenchyma: - elastase can induce apoptosis - cells exposed to oxidants may undergo apoptosis or necrosis
COPD - cellular and biochemical mechanisms Imbalance proteases antiproteases system oxidants antioxidants Destruction of lung parenchyma Small airways disorder
COPD - pathology of peripheral airways • mucus plugging • goblet cell metaplasia • fibrosis • smooth muscle hypertrophy
12 Maximal expiratory effort 6 V´ ( l.s-1 ) 0 Spontaneous breath - 6 0 1 2 3 4 5 Volume from TLC ( l )
100 IRV IRV VT Airflow limit 80 Lung volume (% TLC) VT Normals 60 40 20 40 0 Oxygen consumption (ml.min-1.kg-1)
Emphysema Relatively normal lung region, normal PAO2 Airway narrowing Emphysematous region PAO2 Destruction of capillary V´ V´ CaO2 Relatively normal CaO2 Q´ Q´ Pulm. artery Pulm. vein Normal CaO2 ´
Bronchitis Airway narrowing Relatively normal lung region, normal PAO2 PAO2 normal CaO2 norm V´ V´ CaO2 CaO2 normQ´ norm Q´ Pulm. a. Pulm. v.
10 PaCO2 ( kPa ) 6 4 0 0,5 1,0 1,5 2,0 2,5 3,0 FEV1 ( l )
100 80 60 Oxygen saturation ( % ) 40 20 REM REM REM Sleep period
Components of chronic obstructive pulmonary disease Emphysema but no COPD Emphysema Chronic bronchitis Simple bronchitis Airflow limitation by spirometry Asthma Asthma with no airflow limitation