RESPIRATORY FUNCTIONS

PULMONARY DEFENCE FUNCTIONS (e.g. mucociliary clearance, function of pulmonary macrophages, …) METABOLIC AND ENDOCRINE FUNCTIONS(e.g. production of surfactant, conversion of angiotensin I to angiotensin II, …) RESPIRATORY FUNCTIONS OTHER FUNCTIONS OF RESPIRATORY SYSTEM

RESPIRATORY SYSTEM AIR PASSAGES (CONVECTION) LUNGSASGAS EXCHANGING ORGAN PUMP THAT ENABLES VENTILATION OF THE LUNGS (chest wall with respiratory muscles) TRANSPORT OF O2 AND CO2IN THE BLOOD NERVOUS SYSTEM CONTROLLING THE RESPIRATORY MUSCLES (areas in CNS, efferentmotor neuronsto respiratory muscles, and afferent neurons from various receptors) 1

airways alveoli alveolar-capillary m. DIFFUSION OF O2ACROSS ALVEOLAR-CAPILLARY MEMBRANE capillary DIFFUSION OF O2 FROM CAPILLARIES TO THE CELLS AT REST O2INTAKE~300 ml / min RESPIRATORY QUOTIENT 250 300 STEPS IN THE DELIVERY OF O2 TO THE CELLS VENTILATION OF THE LUNGS inflow TRANSPORT OF O2 IN THE BLOOD UTILIZATION OF O2 BY MITOCHONDRIA via oxidative phosphorylation INTERNAL RESPIRATION CO2OUTPUT~250 ml / min 2

I BASIC PHYSICAL FEATURES OF GASES IIAIR PASSAGES IIIMEASURABLE PARAMETERS DEAD SPACE · · LUNG VOLUMES FUNCTIONAL INVESTIGATIONS · · CHARACTERISTIC PRESSURES IVCOMPOSITION OF ALVEOLAR AIR VALVEOLAR-CAPILLARY MEMBRANE PLAN

RAPIDPRESSURE EQUILIBRATIONin the closedvolume MOVEMENTproceedsfrom the areas of high pressure to theareas of low pressure -DOWNTHE PRESSURE GRADIENT Diffusionof a gasACROSS a BARRIER(between two areas) dependson the PROPERTY of the barrier IN A MIXTURE OF GASES RATE of DIFFUSION ofGAS COMPONENTS depends on theINDIVIDUAL PARTIAL PRESSURE GRADIENTS In a mixture of gasesEQUILIBRATED WITH A LIQUIDeach componentDISSOLVES independently in proportion toits: PARTIAL PRESSURE in the gaseous phase SOLUBILITY in the fluid GENERAL CHARACTERISTICS OF GASES 3

V IDEAL GAS EQUATION n R T = P V If n and T do not change then [J] physical unit of work and energy PV = constant RELATIONS BETWEEN MEASURED QUANTITIES n T P P- pressure [Pa] [mm Hg] n- amount of substance [mol] V - volume [m3] [l] T - absolute temperature [K] R - universalgas constant [J/K.mol] P V = n R T 4

According toDalton´s law: PARTIAL PRESSUREScan be expressedin terms of fractions: P1 = F1Ptot P2= F2 Ptot PARTIAL PRESSURESIN A MIXTURE OF GASES Dalton´s law - law of partial pressures Mixture of two gas components (in a given volume) n1 , n2- amounts of gas substances ntot = n1+ n2 F1 + F2= 1 P1 + P2= Ptot 5

PARTIAL PRESSURES OF GASES IN DRY AIR AT SEA LEVEL PO2 = 760 x 0.21= 160mm Hg PN2 = 760 x 0.78 = 593 mm Hg PCO2=760 x 0.0004= 0.3 mm Hg COMPOSITION OF DRY ATMOSPHERIC AIR O2 20.98 %FO2 0.21 N2 78.06 % FN2  0.78 CO20.04 % FCO2 = 0.0004 other constituents BAROMETRIC (ATMOSPHERIC) PRESSURE AT SEA LEVEL 1 atmosphere = 760 mm Hg 1 kPa = 7.5 mm Hg (torr) 6

DEAD SPACE · · LUNG VOLUMES FUNCTIONAL INVESTIGATION · · CHARACTERISTIC PRESSURES I PHYSICAL FEATURES OF GASES IIAIR PASSAGES IIIMEASURABLE PARAMETERS IVCOMPOSITION OF ALVEOLAR AIR VALVEOLAR-CAPILLARY MEMBRANE

Other functions: air is warmed, cleaned and takes up water vapour respiratory reflex responses to the irritants speech and singing(special function of larynx) TRANSITIONAL ZONE TOTAL ALVEOLAR VOLUME at the end of quiet expiration ~3 l RESPIRATORY BRONCHIOLES ALVEOLAR DUCTS TOTAL AREA ~ 100 m2 AIR PASSAGES ANATOMICAL DEAD SPACE – CONDUCTING ZONE NASAL PASSAGES PHARYNX LARYNX TRACHEA BRONCHI BRONCHIOLES TERMINAL BRONCHIOLES RESPIRATORY ZONE 7

AERODYNAMIC RESISTENCE CAST OF HUMAN AIR PASSAGES TRACHEA BRONCHI BRONCHIOLES TERMINAL BRONCHIOLES 8a

BRONCHUS  <1 mm TERMINAL BRONCHIOLE AUTONOMIC INNERVATION of smooth muscle cells lamina propria ciliated cylindrical epithelium muscarinic receptorsactivation bronchoconstriction mucus visceral pleura β2-adrenergic receptorsactivation bronchodilatation smooth muscle cells gland cartilage BRONCHIAL TONE DURING RESPIRATION blood vessels goblet cell INSPIRATION- bronchodilatation (sympathetic discharge prevails) EXPIRATION- bronchoconstriction (parasympathetic discharge prevails) 9

COLLOID SOLUTIONSWITH DIFFERENT VISCOSITY movement of the mucus with particles MUCOCILIARY CLEARANCE CHRONIC BRONCHITIS CYSTIC FIBROSIS mucoviscidosis Complex genetic disorderreduction of the sol layermainlydue to the defective Cl- channelsin apical membrane of epithelial cells(CFTR - Cystic Fibrosis Transmembrane conductance Regulator). respiratory cilia gel layer sol layer particle 10-20 m 10

∙ · V = VA x f VA = VT x f ALVEOLAR VENTILATION PULMONARY MINUTEVENTILATION · VD = VDx f DEAD SPACEVENTILATION 1.8l/min VT= VA+ VD VT tidal volume~ 500 ml VApart of tidal volume entering alveoli ~ 350 ml VDpart of tidal volume remaining in the dead space~150 ml f = 12/min 4.2l/min 6 l/min Atthe same PULMONARY VENTILATION(6 l/min) ALVEOLAR VENTILATIONat RAPID SHALLOW BREATHING can be SIGNIFICANTLY REDUCED andINADEQUATE in comparison with SLOW DEEP BREATHING 11

ANATOMICALdead space - volume of air passages FUNCTIONAL (total)dead space DEAD SPACE IN RESPIRATORY SYSTEM TOTAL GAS VOLUME NOT EQUILIBRATED WITH BLOOD (without exchange of gasses) ANATOMICAL dead space +total VOLUME of ALVEOLI without functional capillary bed IN HEALTHY INDIVIDUALS both spacesare practically identical 12

during inspirationof pure O2 mid-point of transitional phase VD integrator NITROGEN CURVE EXPIRATION starts Phase I–expired air withpure O2 Phase II-transitional phase(mixture of gasses due to diffusion) Phase III-alveolar phase(alveolar air with decreased value of N2) N2 N2 O2 ANATOMICAL DEAD SPACE MEASUREMENT (single breath N2 test) MODIFIED SPIROMETER reservoir 100 % O2 80 stopcock III one way-valve % N2 II nitrogen meter I 0 pneumotachograph 0.2 transducer system volume expired (l) ? 0.1 0 time (s) 13

VE ……. expired tidal volume in reservoir PCO2E … partial pressure of CO2 in expired air (in reservoir) PCO2A … partial pressure of CO2 in alveolar part of expired air nCO2~PCO2 V ANATOMICAL DEAD SPACE BOHR´SEQUATION PCO2= FCO2 . Ptotal PCO2Acan be measured in the last 10 ml of the expired gas ? VE = VD + VA P V = n R T ………? nCO2 E= nCO2 D+ nCO2 A 14

FUNCTIONAL DEAD SPACE is obtained if alveolar PCO2Ais replaced by arterial partial pressure PCO2a FUNCTIONAL (TOTAL) DEAD SPACE BOHR´S EQUATION HELTHY SUBJECTS - both partial pressuresare nearly identical  FUNCTIONAL dead space equalsANATOMICAL dead space RESPIRATORY DISEASES - numerous alveoli are without functional capillary bedPCO2A PCO2 a 15

SPIROMETRY (direct measurements of lung volumes, capacities, functional investigations, …) STANDARDIZATION of measured values (age, gender, body height, …) inverted bell inspiration expiration water seal subject 16

[ l] INSPIRATORY RESERVEVOLUMEIRV ~2.5 TIDAL VOLUMEVT EXPIRATORY RESERVEVOLUMEERV ~1.7 ~1.3 RESIDUALVOLUMERV DILUTION METHODHe Vr …..reservoir volume ciHe…known initial concentration of He (difference between initial and final amountsof He in reservoir) cfHe…final measured concentration of He He RV RV reservoir (V) reservoir (V) LUNG VOLUMES maximal inspiratory level end of quiet inspiration end of quiet expiration maximal expiratory level n = c V nRV He = ni,r He – nf,r He 17

INSPIRATORY CAPACITY VC TLC >3.0 l FUNCTIONAL RESIDUAL CAPACITY end of quiet expiration ≤25% RV ~1.2 l <3.0 l RV TLC VITAL CAPACITY = VT +IRV + ERV VC ~ 4.7 l TLC TOTAL LUNG CAPACITY =VC + RV ~ 6.0 l maximal inspiratory level maximal expiratory level The largest amount of air that can be expired after maximal inspiration 18

6 5 4 3 FEV1 ≥ 80 % 2 VC 1 PULMONARY VENTILATION RMV(respiratory minute volume) (0.5 l x 12 breathes/min = 6 l/min) 0 1 2 3 4 5 6 7 8 9 MAXIMAL VOLUNTARY VENTILATION(MVV) during time interval 10 s (125-170 l/min) PEAK EXPIRATORY FLOW RATE(PEFR) measured by means of pneumotachograph (~10 l/s) FUNCTIONAL INVESTIGATION OF THE LUNGS TIMED VITAL CAPACITY (FEV1-forced expiratoryvolume per 1 s) volume (l) VC FEV1 time (s) 19

80 35 FEV1 VK 0 1 2 3 4 5 6 7 8 TIMED VITAL CAPACITY FEV1 normal subject 100 FEV1 subject with obstructed airways 50 relative vital capacity (%) FEV1 time (s) TIMED VITAL CAPACITY enables to distinguish RESTRICTIVE disorders(e.g. pulmonary fibrosis)from OBSTRUCTIVEdisorderswith increased airway resistance (e.g. asthma bronchial). 20

DEAD SPACE · · LUNG VOLUMES FUNCTIONAL INVESTIGATION · · CHARACTERISTIC PRESSURES IVCOMPOSITION OF ALVEOLAR AIR I PHYSICAL FEATURES OF GASES IIAIR PASSAGES IIIMEASURABLE PARAMETERS VALVEOLAR-CAPILLARY MEMBRANE

const = P V EXPIRATION INSPIRATION ΔP = Q.R POISEUILLE´S LAW PA>PATM PA<PATM Q …flow rate R... aerodynamic resistance of air passages PA PPL measured curve theoretical curve PTP = PA- PPL ALVEOLAR (INTRAPULMONARY,LUNG) PA TRANSPULMONARY PPL INTRAPLEURAL (INTRATHORACIC) TIME COURSES OF PRESSURES at quiet respiration P.V = const analogy to Ohm´s law VT[l] time ? +1 [mm Hg] -1 -3 ? [mm Hg] -6 21

physiological shunts COMPOSITION OF ALVEOLAR AIR partial pressures in mm Hg EXPIRED AIR INSPIRED AIR ? O2 115.0 CO2 33.0 H2O 47.0 N2 564.0 … O2 158.8 CO2 0.3 N2 601.0 … dead space O2 100.0 CO2 39.0 760 mm Hg 760 mm Hg O2 100.0 CO2 39.0 H2O 47.0 right heart N2 ? left heart 760 mm Hg O2 95.0 CO2 41.0 H2O 47.0 N2 … … O2 40.0 CO2 45.0 H2O 47.0 N2 … … veins arteries O2 40.0 CO2 45.0 H2O 47.0 N2 … … periphery capillaries 22

hyperventilation hypoventilation hyperventilation→ hypocapnia→respiratory alkalosis hypoventilation→ hypercapnia→respiratory acidosis Alveolar PO2 andPCO2at voluntary hypo- and hyperventilation PAO2 100 AtQUIET RESPIRATIONthecomposition of alveolar air remains remarkable constantdue to the relatively great volume of FUNCTIONAL RESIDUAL CAPACITY (~3 l) alveolarPO2andPCO2(mm Hg) 50 PACO2 0 2 4 6 8 10 0 alveolar ventilation (l/min) 23

ALVEOLARAIR PO2 = 100 PCO2= 39 (mm Hg) PULMONARY CAPILLARY ALVEOLAR-CAPILLARY (RESPIRATORY) MEMBRANE diameter about 5 µm 0.75 s time interval of erythrocyte contact with respiratory membrane at rest DIFFUSION OF GASES ACROSS RESPIRATORY MEMBRANE alveolar epithelial cell nucleus RED BLOOD CELL capillary endothelial cell O2 O2 O2 nucleus Hb HbO2 CO2 CO2 CO2 interstitial space 1µm 24

(ml/min) TOTAL SURFACE AREA OF THE ALVEOLAR-CAPILARY MEMBRANEA(~100 m2) ( A :emphysema) DIFFUSION DISTANCE - THICKNESS OF THE BARRIERl (~1 μm) ( l :inflammation, pulmonary edema) PARTIAL PRESSURE DIFFERENCE(PA - Pc) DIFFUSION COEFFICIENT OF THE GASkDdetermined 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) FICK´S LAW – LAW OF DIFFUSION 25

PO2 100 PCO2 40 venous blood PO240 PCO246 mm Hg equilibrated with alveolar pressures mm Hg Δ PO260 mm Hg Δ PCO2 6 mm Hg time 0.75 s time interval of contact of erythrocyte with respiratory membraneat rest TIME COURSESOFCAPILLARYPO2ANDPCO2 DURING EQUILIBRATION WITHALVEOLAR AIR PO2 100 PCO2 40 mm Hg mm Hg 100 PO2 80 60 PCO2 40 26

· CO Vgas– flow of the gas (ml/min) CO2  O2 VCO PA- Pc – partial pressure difference DLCO /PACO (DRIVING FORCE FOR DIFFUSION) INDEX OF DIFFUSING CAPACITYGas CO is suitable for measurement of DLbecause PCO in plasmais negligible. PACOandthe decrease in amount of CO per unit of time in alveoliare measured ( ).  · 0.75 s VCO DLCO17ml/ min/ mm Hg DLO2 21ml/ min/ mm Hg  DLO2increasesduring exercise()andis reducedin pulmonary diseases( A, l) VO2 kDCO2» kDO2 DIFFUSINGCAPACITY OF THE LUNGS DL DLCO2»DLO2

alveolar partial pressure level N2O(nitrous oxide) INERT GAS used for cerebral and coronary blood flow measurements CO(carbon monoxide) AVIDLY BOUND IN ERYTHROCYTE used for assessment of diffusing capacity of the lungs DL EQUILIBRATION OFO2,N2O,ANDCOPARTIAL PRESSURESIN CAPILLARY BLOOD WITH ALVEOLAR PRESSURES O2 N2O relative capillary partialpressures (very rapid equilibration) CO (very slow equilibration) 0.25 0.50 0.75 time (s) time interval of erythrocyte contact with respiratory membrane FICK´S LAW OF DIFFUSION

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RESPIRATORY FUNCTIONS