RESPIRATORY FUNCTIONS OTHER FUNCTIONS OF RESPIRATORY SYSTEM METABOLIC AND ENDOCRINE FUNCTIONS (e.g. production of surfactant, conversion of angiotensin I to angiotensin II, …) PULMONARY DEFENCE FUNCTIONS (e.g. mucociliary clearance, function of pulmonary macrophages, …) RESPIRATORY SYSTEM AIR PASSAGES (CONVECTION) LUNGS AS GAS EXCHANGING ORGAN PUMP THAT ENABLES VENTILATION OF THE LUNGS (chest wall with respiratory muscles) TRANSPORT OF O2 AND CO2 IN THE BLOOD NERVOUS SYSTEM CONTROLLING THE RESPIRATORY MUSCLES (areas in CNS, efferent motor neurons to respiratory muscles, and afferent neurons from various receptors) 1 STEPS IN THE DELIVERY OF O2 TO THE CELLS airways alveoli alveolar-capillary m. capillary UTILIZATION OF O2 BY MITOCHONDRIA via oxidative phosphorylation TRANSPORT OF O2 IN THE BLOOD DIFFUSION OF O2 ACROSS ALVEOLAR-CAPILLARY MEMBRANE DIFFUSION OF O2 FROM CAPILLARIES TO THE CELLS 2 VENTILATION OF THE LUNGS INTERNAL RESPIRATION CO2 OUTPUT ~250 ml / min O2 INTAKE ~300 ml / min AT REST inflow RESPIRATORY QUOTIENT 250 300 · LUNG VOLUMES · FUNCTIONAL INVESTIGATIONS · CHARACTERISTIC PRESSURES · DEAD SPACE I BASIC PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE PLAN GENERAL CHARACTERISTICS OF GASES Diffusion of a gas ACROSS a BARRIER (between two areas) depends on the PROPERTY of the barrier 3 In a mixture of gases EQUILIBRATED WITH A LIQUID each component DISSOLVES independently in proportion to its: PARTIAL PRESSURE in the gaseous phase SOLUBILITY in the fluid IN A MIXTURE OF GASES RATE of DIFFUSION of GAS COMPONENTS depends on the INDIVIDUAL PARTIAL PRESSURE GRADIENTS RAPID PRESSURE EQUILIBRATION in the closed volume MOVEMENT proceeds from the areas of high pressure to the areas of low pressure -DOWN THE PRESSURE GRADIENT RELATIONS BETWEEN MEASURED QUANTITIES P V = n R T If n and T do not change then P V = constant 4 P - pressure [Pa] [mm Hg] n - amount of substance [mol] V - volume [m3] [l] T - absolute temperature [K] R - universal gas constant [J/K.mol] physical unit of work and energy [ J ] V P n T n T V R P = IDEAL GAS EQUATION PARTIAL PRESSURES IN A MIXTURE OF GASES 5 Dalton´s law - law of partial pressures Mixture of two gas components (in a given volume) n1 , n2 - amounts of gas substances Þ ntot = n1 + n2 F1 + F2 = 1 PARTIAL PRESSURES can be expressed in terms of fractions: P1 = F1 Ptot P2 = F2 Ptot According to Dalton´s law: P1 + P2 = Ptot O2 20.98 % FO2 @ 0.21 N2 78.06 % FN2 @ 0.78 CO2 0.04 % FCO2 = 0.0004 other constituents BAROMETRIC (ATMOSPHERIC) PRESSURE AT SEA LEVEL 1 atmosphere = 760 mm Hg PARTIAL PRESSURES OF GASES IN DRY AIR AT SEA LEVEL PO2 = 760 x 0.21 = 160 mm Hg PN2 = 760 x 0.78 = 593 mm Hg PCO2 = 760 x 0.0004 = 0.3 mm Hg 6 1 kPa = 7.5 mm Hg (torr) COMPOSITION OF DRY ATMOSPHERIC AIR I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE AIR PASSAGES ANATOMICAL DEAD SPACE – CONDUCTING ZONE NASAL PASSAGES PHARYNX LARYNX TRACHEA BRONCHI BRONCHIOLES TERMINAL BRONCHIOLES 7 TRANSITIONAL ZONE RESPIRATORY BRONCHIOLES ALVEOLAR DUCTS RESPIRATORY ZONE TOTAL ALVEOLAR VOLUME at the end of quiet expiration ~3 l TOTAL AREA ~ 100 m2 Other functions: air is warmed, cleaned and takes up water vapour respiratory reflex responses to the irritants speech and singing (special function of larynx) Folie7 před cut CAST OF HUMAN AIR PASSAGES TRACHEA BRONCHI BRONCHIOLES TERMINAL BRONCHIOLES 8a AERODYNAMIC RESISTENCE Folie8 předb cut aa ciliated cylindrical epithelium lamina propria visceral pleura smooth muscle cells cartilage blood vessels gland goblet cell mucus 9 AUTONOMIC INNERVATION of smooth muscle cells muscarinic receptors activation Þ bronchoconstriction β2-adrenergic receptors activation Þ bronchodilatation BRONCHUS Æ < 1 mm TERMINAL BRONCHIOLE INSPIRATION - bronchodilatation (sympathetic discharge prevails) EXPIRATION - bronchoconstriction (parasympathetic discharge prevails) BRONCHIAL TONE DURING RESPIRATION MUCOCILIARY CLEARANCE Folie9 před cut a respiratory cilia gel layer sol layer CYSTIC FIBROSIS mucoviscidosis Complex genetic disorder Þ reduction of the sol layer mainly due to the defective Cl- channels in apical membrane of epithelial cells (CFTR - Cystic Fibrosis Transmembrane conductance Regulator). 10 CHRONIC BRONCHITIS movement of the mucus with particles particle COLLOID SOLUTIONS WITH DIFFERENT VISCOSITY I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE f = 12/min VT = VA + VD VD part of tidal volume remaining in the dead space ~ 150 ml 11 4.2 l/min 6 l/min ALVEOLAR VENTILATION VA · = VA x f 1.8 l/min DEAD SPACE VENTILATION VD · = VD x f PULMONARY MINUTE VENTILATION V ∙ = VT x f VT tidal volume ~ 500 ml VA part of tidal volume entering alveoli ~ 350 ml At the same PULMONARY VENTILATION (6 l/min) ALVEOLAR VENTILATION at RAPID SHALLOW BREATHING can be SIGNIFICANTLY REDUCED and INADEQUATE in comparison with SLOW DEEP BREATHING 12 IN HEALTHY INDIVIDUALS both spaces are practically identical DEAD SPACE IN RESPIRATORY SYSTEM TOTAL GAS VOLUME NOT EQUILIBRATED WITH BLOOD (without exchange of gasses) ANATOMICAL dead space - volume of air passages FUNCTIONAL (total) dead space ANATOMICAL dead space + total VOLUME of ALVEOLI without functional capillary bed O2 N2 Folie16a před c cut Folie16a před aa cut stopcock one way-valve nitrogen meter pneumotachograph transducer system 80 0 time (s) 0.1 0.2 I II III ANATOMICAL DEAD SPACE MEASUREMENT VD 13 integrator during inspiration of pure O2 100 % O2 NITROGEN CURVE Phase I – expired air with pure O2 Phase II - transitional phase (mixture of gasses due to diffusion) Phase III - alveolar phase (alveolar air with decreased value of N2) mid-point of transitional phase 0 EXPIRATION starts ? reservoir N2 MODIFIED SPIROMETER (single breath N2 test) ANATOMICAL DEAD SPACE VE = VD + VA 14 PCO2A can be measured in the last 10 ml of the expired gas PCO2 A … partial pressure of CO2 in alveolar part of expired air PCO2 E … partial pressure of CO2 in expired air (in reservoir) VE ……. expired tidal volume in reservoir P V = n R T nCO2 ~ PCO2 V ? PCO2 = FCO2 . Ptotal nCO2 E = nCO2 D + nCO2 A BOHR´S EQUATION ………? FUNCTIONAL (TOTAL) DEAD SPACE 15 FUNCTIONAL DEAD SPACE is obtained if alveolar PCO2A is replaced by arterial partial pressure PCO2a BOHR´S EQUATION HELTHY SUBJECTS - both partial pressures are nearly identical Þ FUNCTIONAL dead space equals ANATOMICAL dead space RESPIRATORY DISEASES - numerous alveoli are without functional capillary bed Þ PCO2A < PCO2 a I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE Folie10 před cut water seal subject inspiration expiration inverted bell 16 STANDARDIZATION of measured values (age, gender, body height, …) SPIROMETRY (direct measurements of lung volumes, capacities, functional investigations, …) Folie11 před cut bb LUNG VOLUMES TIDAL VOLUME VT 17 maximal inspiratory level RESIDUAL VOLUME RV ~1.3 maximal expiratory level end of quiet expiration DILUTION METHOD He ci He …known initial concentration of He cf He …final measured concentration of He Vr …..reservoir volume nRV He = ni,r He – nf,r He n = c V EXPIRATORY RESERVE VOLUME ERV ~1.7 INSPIRATORY RESERVE VOLUME IRV ~2.5 [ l ] reservoir (V) RV end of quiet inspiration He reservoir (V) RV (difference between initial and final amounts of He in reservoir) Folie11 před cut bb maximal expiratory level maximal inspiratory level The largest amount of air that can be expired after maximal inspiration VC VITAL CAPACITY = VT + IRV + ERV ~ 4.7 l VC 18 TLC TOTAL LUNG CAPACITY = VC + RV ~ 6.0 l TLC ~1.2 l RV FUNCTIONAL RESIDUAL CAPACITY <3.0 l end of quiet expiration RV TLC ≤ 25% INSPIRATORY CAPACITY >3.0 l I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE Folie13 před cut 0 1 3 2 4 5 6 7 8 9 time (s) 1 2 3 4 5 6 FUNCTIONAL INVESTIGATION OF THE LUNGS TIMED VITAL CAPACITY (FEV1 - forced expiratory volume per 1 s) FEV1 VC PULMONARY VENTILATION RMV (respiratory minute volume) (0.5 l x 12 breathes/min = 6 l/min) PEAK EXPIRATORY FLOW RATE (PEFR) measured by means of pneumotachograph (~10 l/s) MAXIMAL VOLUNTARY VENTILATION (MVV) during time interval 10 s (125-170 l/min) 19 ≥ FEV1 VC 80 % Folie14 před cut 0 1 2 3 4 5 6 7 8 50 100 FEV1 subject with obstructed airways FEV1 time (s) TIMED VITAL CAPACITY FEV1 20 TIMED VITAL CAPACITY enables to distinguish RESTRICTIVE disorders (e.g. pulmonary fibrosis) from OBSTRUCTIVE disorders with increased airway resistance (e.g. asthma bronchial). 80 35 FEV1 VK normal subject I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE Folie17 přech a cut 3 Folie17 přech a cut 1 VT [l] time 21 P.V = const PA ALVEOLAR (INTRAPULMONARY, LUNG ) PA PPL INTRAPLEURAL (INTRATHORACIC) PPL PTP = PA- PPL TRANSPULMONARY TIME COURSES OF PRESSURES at quiet respiration INSPIRATION EXPIRATION POISEUILLE´S LAW ΔP = Q.R Q … flow rate R ... aerodynamic resistance of air passages analogy to Ohm´s law Folie17 přech a cut 2 -3 -6 [mm Hg] [mm Hg] +1 -1 PA > PATM PA < PATM V const P = measured curve theoretical curve ? ? I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE obr 12 přech cut COMPOSITION OF ALVEOLAR AIR 760 mm Hg INSPIRED AIR EXPIRED AIR dead space O2 100.0 CO2 39.0 H2O 47.0 right heart left heart veins arteries periphery capillaries 22 760 mm Hg partial pressures in mm Hg 760 mm Hg N2 O2 158.8 CO2 0.3 N2 601.0 … O2 115.0 CO2 33.0 H2O 47.0 N2 564.0 … O2 95.0 CO2 41.0 H2O 47.0 N2 … … O2 40.0 CO2 45.0 H2O 47.0 N2 … … O2 40.0 CO2 45.0 H2O 47.0 N2 … … physiological shunts O2 100.0 CO2 39.0 ? ? Alveolar PO2 and PCO2 at voluntary hypo- and hyperventilation 23 50 100 2 4 6 8 10 alveolar ventilation (l/min) PAO2 hyperventilation → hypocapnia → respiratory alkalosis hyperventilation hypoventilation → hypercapnia → respiratory acidosis hypoventilation PACO2 0 0 At QUIET RESPIRATION the composition of alveolar air remains remarkable constant due to the relatively great volume of FUNCTIONAL RESIDUAL CAPACITY (~3 l) I PHYSICAL FEATURES OF GASES II AIR PASSAGES III MEASURABLE PARAMETERS · LUNG VOLUMES · FUNCTIONAL INVESTIGATION · CHARACTERISTIC PRESSURES · DEAD SPACE IV COMPOSITION OF ALVEOLAR AIR V ALVEOLAR-CAPILLARY MEMBRANE obr 13 přech cut nucleus RED BLOOD CELL O2 O2 Hb HbO2 CO2 CO2 1 µm 24 DIFFUSION OF GASES ACROSS RESPIRATORY MEMBRANE ALVEOLAR-CAPILLARY (RESPIRATORY) MEMBRANE interstitial space ALVEOLAR AIR PO2 = 100 PCO2 = 39 (mm Hg) alveolar epithelial cell time interval of erythrocyte contact with respiratory membrane at rest 0.75 s PULMONARY CAPILLARY diameter about 5 µm capillary endothelial cell nucleus O2 CO2 PARTIAL PRESSURE DIFFERENCE (PA - Pc) DIFFUSION COEFFICIENT OF THE GAS kD determined by molecular mass, solubility of the gas in the respiratory membrane (¯ kD : pulmonary fibrosis). FACTORS AFFECTING RATE OF DIFFUSION OF GASE IN THE LUNGS (O2 or CO2) DIFFUSION DISTANCE - THICKNESS OF THE BARRIER l (~1 μm) ( l : inflammation, pulmonary edema) TOTAL SURFACE AREA OF THE ALVEOLAR-CAPILARY MEMBRANE A (~ 100 m2 ) (¯ A : emphysema) FICK´S LAW – LAW OF DIFFUSION 25 (ml/min) obr 16 přech cut PO2 PCO2 PO2 100 PCO2 40 mm Hg venous blood PO2 40 PCO2 46 mm Hg 40 100 60 80 mm Hg 26 time 0.75 s time interval of contact of erythrocyte with respiratory membrane at rest Δ PO2 @ 60 mm Hg Δ PCO2 @ 6 mm Hg equilibrated with alveolar pressures PO2 100 PCO2 40 mm Hg TIME COURSES OF CAPILLARY PO2 AND PCO2 DURING EQUILIBRATION WITH ALVEOLAR AIR DIFFUSING CAPACITY OF THE LUNGS DL Vgas – flow of the gas (ml/min) · (DRIVING FORCE FOR DIFFUSION) PA- Pc – partial pressure difference O2 CO2 0.75 s CO DLO2 21 ml/ min/ mm Hg DLCO 17 ml/ min/ mm Hg DLCO2 » DLO2 DLCO /PACO VCO · DLO2 increases during exercise ( ) and is reduced in pulmonary diseases (¯ A, l ) × VO 2 kDCO2 » kDO2 INDEX OF DIFFUSING CAPACITY Gas CO is suitable for measurement of DL because PCO in plasma is negligible. PACO and the decrease in amount of CO per unit of time in alveoli are measured ( ). × × VCO EQUILIBRATION OF O2, N2O, AND CO PARTIAL PRESSURES IN CAPILLARY BLOOD WITH ALVEOLAR PRESSURES O2 N2O CO time (s) 0.25 0.50 0.75 (very rapid equilibration) (very slow equilibration) alveolar partial pressure level time interval of erythrocyte contact with respiratory membrane FICK´S LAW OF DIFFUSION CO (carbon monoxide) AVIDLY BOUND IN ERYTHROCYTE used for assessment of diffusing capacity of the lungs DL N2O (nitrous oxide) INERT GAS used for cerebral and coronary blood flow measurements END