RESPIRATORY FUNCTIONS MECHANICS OF RESPIRATORY SYSTEM GAS TRANSPORT RESPIRATORY SYSTEM •STOMATOLOGY • STEPS IN THE DELIVERY OF O2 TO THE CELLS •airways •alveoli • •alveolar-capillary m. •capillary •UTILIZATION OF O2 BY MITOCHONDRIA •TRANSPORT OF O2 IN THE BLOOD •DIFFUSION OF O2 ACROSS ALVEOLAR-CAPILLARY MEMBRANE • •DIFFUSION OF O2 FROM CAPILLARY TO THE CELLS • •1 •VENTILATION OF THE LUNGS INTERNAL RESPIRATION •CO2 OUTPUT ~250 ml / min • O2 UPTAKE ~300 ml / min •AT REST • • • • •I PHYSIOLOGY OF AIR PASSAGES •II BASIC MEASURABLE PARAMETERS • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE •III ACTIVE AND PASSIVE FORCES •VI TRANSPORT OF O2 AND CO2 IN THE BLOOD •AIR PASSAGES •ANATOMICAL DEAD SPACE –CONDUCTING ZONE •NASAL PASSAGES •PHARYNX •LARYNX •TRACHEA •BRONCHI •BRONCHIOLES •TERMINAL BRONCHIOLES •2 • • • • • • • • • •RESPIRATORY ZONE •(GAS EXCHANGE) •Total alveolar area ~100 m2 • •Other physiological functions: • air is warmed, cleaned and takes up water vapour • respiratory reflex responses to the irritants • speech and singing (function of larynx) • • • Folie7 před cut •CAST OF HUMAN AIR PASSAGES •TRACHEA •BRONCHI •BRONCHIOLES • • •TERMINAL BRONCHIOLES •3 • •AERODYNAMIC RESISTENCE Folie8 předb cut aa •ciliated cylindrical epithelium •lamina propria •visceral pleura •smooth muscle cells •cartilage •blood vessels •gland •goblet cell •mucus •4 •AUTONOMIC INNERVATION of smooth muscle cells •Muscarinic receptors: Acetylcholine activates bronchoconstriction •b-adrenergic receptors: Noradrenaline activates bronchodilatation •BRONCHUS • •Æ < 1 mm •TERMINAL BRONCHIOLE • • • • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) • •f = 12/min •VT = VA + VD •VD part of tidal volume remaining in the dead space ~ 150 ml •5 •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 •6 • •IN HEALTHY INDIVIDUALS •both spaces are practically identical • DEAD SPACE •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 • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) Folie10 před cut •SPIROMETRY •water seal •subject • • • •inspiration •expiration •inverted bell •7 •(measurements of lung volumes, capacities, functional investigations, …) Folie11 před cut bb •LUNG VOLUMES • •TIDAL VOLUME VT • •EXPIRATORY RESERVE VOLUME ERV • •~1.7 • •8 •maximal inspiratory level • • • • •RESIDUAL VOLUME RV • ~1.3 •maximal expiratory level •end of quiet expiration •DILUTION METHOD He •INSPIRATORY RESERVE VOLUME IRV • •~2.5 •[l ] •end of quiet inspiration • • •He •reservoir (Vr) •RV • • •ci •3 Calculation of residual volume RV from the initial and final He concentrations in reservoir (ci , cf). • • • •He •reservoir (V) •RV • • •cf • Þ Equilibration of the air in the residual volume and reservoir •Principle of method: 1 Maximal expiration, 2 Repeated inspiration from and expiration into a reservoir (known volume Vr) with inert gas He (known concentration ci) Folie11 před cut bb • •maximal expiratory level • • •maximal inspiratory level • •VC - the largest amount of air that can be expired after maximal • inspiration • •VC •VITAL CAPACITY = VT + IRV + ERV •~ 4.7 l •VC •9 • •TLC •TOTAL LUNG CAPACITY = VC + RV •~ 6.0 l •TLC • • •~1.2 l •RV • •FUNCTIONAL RESIDUAL CAPACITY •<3.0 l • •end of quiet expiration • •INSPIRATORY CAPACITY •>3.0 l • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) •FUNCTIONAL INVESTIGATION OF THE LUNGS •TIMED VITAL CAPACITY (FEV1 - forced expiratory volume per 1 s) • •PULMONARY MINUTE VENTILATION RMV (respiratory minute volume) at rest (0.5 l x 12 breathes/min = 6 l/min) • •PEAK EXPIRATORY FLOW RATE (PEFR) (~10 l/s) • •MAXIMAL VOLUNTARY VENTILATION (MVV) (125-170 l/min) • •10 • •0 •1 •3 •2 •4 •5 •6 •7 •8 •9 •time (s) •1 •2 •3 •4 •5 •6 • •FEV1 • • •VC • •≥ •FEV1 • •VC •80 % • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) Folie17 přech a cut 3 Folie17 přech a cut 1 Folie17 přech a cut 2 •VT [l] •time •-3 •-6 •[mm Hg] •[mm Hg] •+1 •-1 •11 • P.V = const • •PA • ALVEOLAR (INTRAPULMONARY, LUNG) •PA •PPL •INTRAPLEURAL (INTRATHORACIC) •PPL • •TIME COURSE OF PRESSURES AT QUIET RESPIRATION •INSPIRATION •EXPIRATION •PA < PATM • PA > PATM • •measured curve •theoretical curve •? •? • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) FORCES PARTICIPATING IN RESPIRATION •12 • QUIET RESPIRATION •EXPIRATION - only passive (elastic) forces are in action • INSPIRATION - active forces of inspiratory muscles prevail • •PASSIVE FORCES represented by: •ACTIVE FORCES performed by respiratory muscles • • •lungs elasticity • •chest elasticity • • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) • obr 2a cut • RESPIRATORY MUSCLES •accessory muscles •external intercostals •diaphragm •internal intercostals •abdominal muscles •EXPIRATORY •INSPIRATORY • •13 •INSPIRATORY muscles • •QUIET breathing •diaphragm (> 80 % ) •external intercostals (< 20 % ) • • •EXPIRATORY muscles •14 •internal intercostals •muscles of the anterior abdominal wall (abdominal recti, …) • • •Only at FORCED breathing •accessory inspiratory muscles (mm. scalene) • •FORCED breathing •in addition • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) •1 kPa = 7.5 mm Hg •LUNGS ELASTICITY • •INHERENT TISSUE ELASTICITY •(elastin and collagen fibres) •SURFACE TENSION FORCES •air-liquid interface in alveoli •15 obr 3 přech • •200 •150 •100 •50 •0 •0.4 •ALVEOLAR PRESSURE (kPa) •0.8 •1.2 •1.6 •2.0 •HYSTERESIS LOOP •INFLATION •DEFLATION •opening pressure • • •AIR • •LUNGS ELASTICITY • • • • • •SALINE • • •16 • • • • • • • • • •P pressure (transmural DP) •r radius •T surface tension •LAW OF LAPLACE •spherical structures •EXPANSION OF ALVEOLI • • •P1 > P2 •P1 •P2 • • •COLLAPSE OF ALVEOLI - ATELECTASIS • • • •P •r •T • • • • •r •T •P •2 •= • • • •? •PATHOLOGY •17a •SURFACTANT •SURFACE TENSION LOWERING AGENT obr 5 přech •ALVEOLAR EPITHELIAL CELLS •macrofage •fatty acids, choline, glycerol, amino acids, etc.) •surfactant • surfactant cycle • exocytosis of lamellar bodies • • •PHOSPHOLIPID •dipalmitoyl fosfatidyl cholin • TYPE II •specialized granular epithelial cells •PRODUCTION OF SURFACTANT •TYPE I •thin epithelial cells •DIFFUSION OF GASSES • •EFFECT MAINLY IN THE EXPIRED POSITION •200 •150 •100 •50 •0 •0.4 •ALVEOLAR PRESSURE (kPa) •0.8 •1.2 •1.6 •2.0 •HYSTERESIS LOOP •INFLATION •DEFLATION •opening pressure • • •AIR • •SALINE •Factors involved in HYSTERESIS LOOP •17b •LAPLACE LAW (responsible for high opening pressure of alveoli) • •Dynamic changes in the DENSITY of surfactant molecules during INSPIRATION and EXPIRATION • • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) obr 6 přech b cut •COMPLIANCE (VOLUME STRETCHABILITY) •alveolar pressure DPA (mm Hg) •0 •100 •50 •150 •200 •-50 •-100 •0 •+1 •-1 •+2 •+3 •-2 •VC •RV •FRC •relaxation volume • •18 •relaxation pressure curve •STATIC MEASUREMENT IN CLOSED SYSTEM •V •P •DP •DV • • • • •compliance is increased •¯ stiffness of the tissue • •compliance is decreased • stiffness of the tissue • •P •V •C •D •D •= •end of quiet expiration •Valsalva •maneuver •Müller´s •maneuver • • •TOTAL RESPIRATORY SYSTEM (lungs and chest) • • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) •ELASTIC (STATIC) WORK •to overcome the elastic forces of the chest and lungs •DYNAMIC WORK •to overcome the resistance of air passages during the air movement – AERODYNAMIC RESISTANCE (~ 28%) • •to overcome the friction during mutual movement of inelastic tissues – VISCOUS RESISTANCE (~ 7%) • • •19 •TOTAL WORK OF RESPIRATORY MUSCLES AT QUIET BREATHING •(65%) •(35%) • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) • • • 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 GASSES 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 •20 •1 kPa = 7.5 mm Hg (torr) •COMPOSITION OF DRY ATMOSPHERIC AIR 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 •21 •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 • •22 • •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 •composition of alveolar air remains constant (functional residual capacity ~3.0 l) • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) obr 13 přech cut •nucleus •RED BLOOD CELL •O2 • •O2 • • • •O2 • •Hb •HbO2 •CO2 • •CO2 •CO2 • ~1 µm • • • • • • •23 • • •ALVEOLAR-CAPILLARY (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 • •nucleus •capillary endothelial cell • •DIFFUSION OF GASES 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 • •24 •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 • • •equalization with alveolar pressures •PO2 100 •PCO2 40 •mm Hg •TIME COURSE OF CAPILLARY PO2 AND PCO2 DURING GRADUAL EQUILIBRATION WITH ALVEOLAR AIR • • • • •I AIR PASSAGES •II MEASURABLE PARAMETERS •LUNG VOLUMES •FUNCTIONAL INVESTIGATION •CHARACTERISTIC PRESSURES •· •· •· •· •DEAD SPACE • •IV COMPOSITION OF ALVEOLAR AIR •V ALVEOLAR-CAPILLARY MEMBRANE • RESPIRATORY MUSCLES • LUNGS ELASTICITY • COMPLIANCE • WORK OF BREATHING •III ACTIVE AND PASSIVE FORCES •· •· •· •· •VI TRANSPORT OF GASSES (O2 and CO2) obr 17 přech b cut obr 17 přech a cut •HAEMOGLOBIN •α •α •β •β •1 nm •Fe •Fe •N •N •N •N •N •N •N •N •DEOXY •OXY •N •N •N •polypeptide chain •polypeptide chain •O2 •Fe3+ (methaemoglobin) •oxidation •25 •fetal Hb •γ •γ •Fe2+ • • • •tetramer •porfyrin •Hb4 + 4 O2 ↔ Hb4O8 •oxygenation •O2–HAEMOGLOBIN DISSOCIATION CURVE •100 •50 •PO2 (mm Hg) • •CO Hb •26 •myoglobin fetal Hb •50 •0 •50 •100 •0 • •plateau area •steep portion •↓ pH, ↑ CO2 •↑ BPG (2,3-bisphosphoglycerate) •↑ temperature •methaemoglobin •BOHR´S EFFECT (¯ pH, CO2) •physiological range •v • • •a • •P50 •physically dissolved O2 (1.4%) • •PCO (mm Hg) obr 19 přech cut •TRANSPORT OF CO2 •Cl- •HAMBURGER CHLORIDE SHIFT •H2 CO3 •CO2 + H2O •CA •CA – carbonic anhydrase •H2O •27 •HCO3- • H+ + • H+ + deoxyHb- •H-deoxyHb • • •HCO3- •Cl- •CO2 • • obr 20 přech b cut obr 20 přech a cut •HbO2 • • •CO2 •O2 •28 •CO2 •CO2 •CO2 physically dissolved (~5.3%) • • • • •CO2 • •O2 •Cl- •HCO3- • •CO2+ H2O •HCO3- + H+ •CO2 + H 2O HCO3- + H+ (~89%) • •Hb.CO2 •CO2 + Hb-NH2 Hb.NH-COO- (carbamino-Hb) (~5.3 %) • • •60% in plasma, 29% in red blood cell • obr 21 přech copy •HALDANE EFFECT • CO2 DISSOCIATION CURVE •deoxygenated blood •5 •10 •15 •20 •25 •30 •10 •20 •30 •40 •50 •60 •70 •PCO2 (mm Hg) •physically dissolved CO2 • •a •v • • •oxygenated blood •29 • • •deoxygenated blood in peripheral tissues •oxygenated blood in the lungs •CO2 + H2O H2CO3 H+ + HCO3- •Hb- + H+ HHb •TISSUES: DEOXY-Hb binds H+ more readily (weaker acid) Þ ↑ amount of chemically bound CO2 •? •physiological values •in arterial and venous blood •Hb.NH.COO- •1 •Hb- + H+ HHb •2 •LUNGS: H+ is released from OXY-Hb Þ ↓ amount of chemically bound CO2 •DEOXY-Hb •END