1. Pathophysiology of airway and lung defensive mechanisms Prof. Jan Hanacek

2. Classification of airway and lung defensive mechanisms A.Reflexive B.Non-reflexive Ad A. - changes of breathing pattern - cough reflex - apnoic reflex - sneezing - expiration reflex - aspiration reflex - larygospasm, bronchospasm

3. Ad B. Physical defensive mechanisms – air conditioning, aerodynamic filter, electrostatic filter Immune mechanisms – cellular and humoral (back to microbiology and immunology) Mucociliary clearance – ciliary cinetics, rheology and amount of mucus, morphology of bronchial mucosa Airway and lung surface liquid – mucus, surfactant Protease-antiprotease system –  production of proteses and/or  production of antiproteases Oxidants-antioxidants system –  production of oxidants and/or  production of antioxidants

4. Disturbances of reflexive defensive mechanisms a) Enormously enhaced  Causes: - inflammation of airway mucosa, - inhalation of irritant/toxic gases, - inhalation of foreign body, - stimulation of centres regulating breathing, e.g. „cough centre“  Results: - dissemination of infection in the lung, - damage of airway mucosa and rupture of alveolar wall, pneumothorax - fracture of ribs and/or vertebrates - nausea, vomitus, headache - incontinence of urine - chest pain - negative effects on heart function, on circulation, and gas exchange in lung – „cough syncope“ - disturbances of sleep, food intake - general exhaustion

5. Disturbances of reflexive defensive mechanisms b) Weak or absent (especially cough) Causes : - functional and/or structural damage of afferent branche, - central network - efferents/efectors e.g. due to brain damage, diabetic neuropathy, inhibition of central part of defensive mechanisms by drugs Results : - mucus accumulation with incresed concentration of infective/toxic factors - dissemination of infetion/toxins into undamaged lung regions - disturbances of lung ventilation, distribution of air in the lung - disturbances of ventilation-perfusion ratio - hypoxemia  hypoxia, hypercapnia, respiratory failure

6. Disturbances of non-reflexive defensive mechanisms Physical defensive mechanisms insufficiency of upper airway:  Causes: - structural changes of upper airway – inherited, acquired - chronic inflammation of upper airway  Results: - chronic inflammation of lower airway Insuficiency of immune mechanism of airway  Causes: - insufficiency of cellular defence (due to immune cells abnormalities) - insufficiency of humoral defence (  bacteriostatic lung proteins-e.g. lysozomes, transferrin, lactoferrin, local immunoglobulins  Results: - decresed defence of the airway and lung against infections

7. Disturbances of non-reflexive defensive mechanisms Disturbances of mucociliary clearance - MCC Rate of MCC of airway is important to keep the lungs free from toxic, allergic and infectious materials  Causes:- inherited cilia disfunction, e.g. Kartagener’s sy. - acquired disfunction, e.g. due to airway infection (rhino- viruses), toxic damage by air pollutants (SO 2, NO x, O 3 ) cigarette smoke - changes in amount and rheology of airway mucus - some drugs (beta-blockers) These processes lead to reduced or abnormal cilia beating, discontinuity and/or size of mucus blanket, damage of cilliated cells  Results:- Congenital Dyskinetic Cilia Syndromes (Immotile Cilia, Ciliary Dysfunction Sy., - Acquired dysfunction of ciliary mechanism

8. Disturbances of protease-antiprotease system Tissue proteases: elastase, collagenase, cathepsin G, proteinase 3 Antiprotease system: alpha-1 antitrypsin, antileukoproteinase, alpha-2-macroglobulin, antichymotrypsin, neutrophil endopeptidase Disorder of protease-antiprotease balance  Causes: a)Increased production of proteases – e.g. released from Ne, macrophages, by inflammation, air pollutants a)Deficiency of antiproteases – iherited or acquired deficiency of alpha-1-antitrypsin a)Both of them  Results: development of lung emphysema

9. Disorder of oxidant – antioxidant system Oxidants: superoxid anion, hydrogen peroxid, hydroxyl radical, siglet molecular oxygen Antioxidants: supeoxid dismutase, catalase, glutathioperoxidase, vitamins – C, E, A trace metals – Se, Zn, Cu Mn Causes: Incresed production of oxidants - hyperoxia, inflammation, carcinogenesis, aging, radiation damage Decreased concentration of antioxidats