1. PULMONARY MECHANICS GAS TRANSPORT

2. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

3. FORCES PARTICIPATING IN RESPIRATION 1 QUIET RESPIRATION EXPIRATION - passive (elastic) forces only INSPIRATION - active forces of inspiratory muscles prevail PASSIVE FORCES represented by: ACTIVE FORCES performed by respiratory muscles lungs elasticity chest elasticity

4. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

5. RESPIRATORY MUSCLES accessory muscles external intercostals diaphragm internal intercostals abdominal muscles EXPIRATORY INSPIRATORY 2a

6. INSPIRATORY muscles QUIET breathing diaphragm (≥ 80 % ) external intercostals (≤ 20 % ) accessory inspiratory muscles ( scalene muscles, … ) FORCED breathing 2b EXPIRATORY muscles internal intercostals muscles of the anterior abdominal wall (abdominal recti, …) Only at FORCED breathing

7. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

8. 1 kPa = 7.5 mm Hg LUNGS ELASTICITY 3 200 150 100 50 0 0.4 VOLUME (ml) INTRAPULMONARY PRESSURE (kPa) 0.81.21.62.0 HYSTERESIS LOOP INFLATION DEFLATION opening pressure AIR LUNGS ELASTICITY INHERENT TISSUE ELASTICITY (elastin and collagen fibres) SURFACE TENSION FORCES (physical properties of air-liquid interface) SALINE FILLING EMPTYING

9. 4 P distending pressure (transmural  P ) r radius T surface tension LAW OF LAPLACE spherical structures BULLOUS EMPHYSEMA EXPANSION OF ALVEOLI P 1 > P 2 P1P1 P2P2 COLLAPSE OF ALVEOLI P r T r T P 2  ATELECTASIS ? PATHOLOGY

10. INFANT RESPIRATORY DISTRESS SYNDROME 5a5a PATCHY ATELECTASIS AFTER CARDIAC SURGERY SURFACTANT SURFACE TENSION LOWERING AGENT 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 EFFECT MAINLY IN THE EXPIRED POSITION TYPE I thin epithelial cells DIFFUSION OF GASSES

11. 200 150 100 50 VOLUME (ml) 0 0.4 ALVEOLAR PRESSURE (kPa) 0.81.21.62.0 HYSTERESIS LOOP INFLATION DEFLATION opening pressure AIR SALINE FILLING EMPTYING Factors involved in HYSTERESIS LOOP 5b LAPLACE LAW (opening pressure of alveoli) Dynamic changes in the DENSITY OF SURFACTANT MOLECULES during inspiration and expiration

12. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

13. COMPLIANCE (VOLUME STRETCHABILITY) alveolar pressure  P A (mm Hg) 0 100 50 150200-50-100 0 +1 +2 +3 -2 change of the volume  V ( l ) VC RV FRC relaxation volume 18 relaxation pressure curve STATIC MEASUREMENT IN CLOSED SYSTEM maximal expiratory curve maximal inspiratory curve V P PP VV compliance is increased  stiffness of the tissue compliance is decreased  stiffness of the tissue P V C    end of quiet expiration Valsalva´s maneuver Müller´s maneuver TOTAL RESPIRATORY SYSTEM (lungs and chest)

14. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

15. ELASTIC (STATIC) WORK CLOSED SYSTEM 0 0-15 pressure ΔP (mm Hg) 1 2 +15 lung volume  V (l) P PL PAPA P TP 7 TV 500 ml elastic force of the chest is zero (P A -P PL ) relaxation pressure curve CHEST relaxation pressure curve LUNGS expiratory reserve volume ? elastic forces of the chest and lungs act in the same direction relaxation pressure curve TOTAL SYSTEM W ELAST (J) TOTAL SYSTEM intrapulmonary pressure P A LUNGS transpulmonary pressure P TP = P A - P PL CHEST intrapleural pressure P PL elastic forces of the chest and lungs are in equilibrium

16. W TOTAL ELASTIC insp = W LUNG + (-W CHEST ) STRETCHING against elastic forces of the lungs ELASTIC RECOIL of the chest 8a TOTAL ELASTIC (STATIC) WORK OF INSPIRATORY MUSCLES AT QUIET INSPIRATION (V ~ 500 ml) ELASTIC FORCES OF THE CHEST HELP inspiratory muscles to increase thoracic cavity

17. ACTIVE AND PASSIVE (ELASTIC) FORCES IN RESPIRATORY SYSTEM PAPA F elast-lungs P PL STATES OF BALANCE RESPIRATORY SYSTEM (LUNGS and CHEST) RESPIRATORY SYSTEM : elastic forces of lungs and chest are balanced 8b VTVT VTVT tidal volume at quiet inspiration (~500 ml) F muscle INSPIRATION CHEST CHEST: elastic force of the chest alone is zero at ΔV~ 1 l LUNGS LUNGS: elastic force of the lungs is zero only when P PL = P ATM ( pneumothorax ) 0 0 P ATM air ways F elast-chest

18. ELASTIC (STATIC) WORK to overcome the elastic forces of the lungs and chest DYNAMIC WORK to overcome the resistance of air passages during the air movement – AERODYNAMIC RESISTANCE ( ~ 28%) to overcome the friction during the mutual movement of inelastic tissues – VISCOUS RESISTANCE ( ~ 7%) 9a (total work of respiratory muscles) TOTAL WORK OF BREATHING (65%) (35%)

19. RESISTANCE OF AIR PASSAGES HAGEN-POISEUILLE´S LAW (laminar flow Q) 9b LAMINAR FLOW TURBULENT FLOW REYNOLDS NUMBER Re < 2000 < Re Ohm´s law l … length r … radius η … viscosity r … radius v … velocity ρ … density η … viscosity Critical velocity

20. TOTAL WORK OF RESPIRATORY MUSCLES [J] DURING RESPIRATORY CYCLE AT QUIET BREATHING 1.5 3.0 W DYN is finally transformed into heat energy (loss of energy) W DYN W DYN = W DYN insp + W DYN expir W INSPIR = W ELAST + W DYN insp W DYN insp ± W ELAST W EXPIR = -W ELAST + W DYN expir W DYN expir change in pressure ΔP (mm Hg) change in volume (ml) W INSPIR = W ELAST + W DYN insp W EXPIR = - W ELAST + W DYN expir 0 500 DYNAMIC WORK W DYN is done to overcome aerodynamic resistance frictional (viscose) resistance 10 DYNAMIC PRESSURE-VOLUME DIAGRAM

21. 1 kPa = 7.5 mm Hg change of volume (l) 0 1 0.50.5 change in pressure (kPa) 0.60.60.40.40.20.2 I E 11 NORMAL LUNGS elastic work INCREASED RESISTANCE OF AIR PASSAGES OBSTRUCTIVE LUNG DISEASE (asthma bronchial) changes in pressure (kPa) 1 0 0.60.60.40.40.20.2 change of volume (l) additional work of expiratory muscles I E CLINICAL IMPLICATION Expiratory muscles are active to overcome the resistance of air passages

22. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

23. HAEMOGLOBIN α α β β 1 nm Fe N N N N N N N N DEOXY OXY NNN polypeptide chain O2O2 Fe 3 + (methaemoglobin) oxidation Hb 4 + 4 O 2 ↔ Hb 4 O 8 oxygenation HAEM 1212 fetal Hb γ γ Fe 2+ tetramer porfyrin

24. O 2 – HAEMOGLOBIN DISSOCIATION CURVE O 2 saturation of haemoglobin (%) 100 50 P O2 (mm Hg) deoxyHb - + H + → H-Hb CO Hb 1313 myoglobin fetal Hb BOHR EFFECT (↓pH, ↑CO 2 ) 50 0 100 0 plateau area steep portion pH, CO 2 ↑BPG (2,3-bisphosphoglycerate) ↑temperature CO saturation of haemoglobin (%) physically dissolved O 2 (1.4%) methaemoglobin physiological range v a P 50 P CO (mm Hg)

25. I. PULMONARY MECHANICS RESPIRATORY MUSCLES LUNGS ELASTICITY COMPLIANCE WORK OF BREATHING II. TRANSPORT OF GASES O 2 CO 2

26. TRANSPORT OF CO 2 HAMBURGER CHLORIDE SHIFT H 2 CO 3 CO 2 + H 2 O CA CA – carbonic anhydrase H2OH2O 1414 HCO 3 - H + + H + + deoxy Hb - H- deoxy Hb Cl - HCO 3 - Cl - CO 2

27. HbO 2 CO 2 O2O2 15 CO 2 CO 2 physically dissolved (~5.3%) CO 2 O2O2 H2OH2O Cl - HCO 3 - NaHCO 3 Na + K+K+ KHCO 3 CO 2 + H 2 O HCO 3 - + H + CO 2 + H 2 O HCO 3 - + H + (~89.3%) Hb.CO 2 CO 2 + Hb-NH 2 Hb.NH-COO - (carbamino-Hb) (~5.3%) ~60% in plasma, ~29% in red blood cell

28. HALDANE EFFECT CO 2 DISSOCIATION CURVE deoxygenated blood 5 10 15 20 25 30 102030 40 506070 P CO2 (mm Hg) physically dissolved CO 2 a v oxygenated blood 16 deoxygenated blood in peripheral tissues oxygenated blood in the lungs CO 2 + H 2 O H 2 CO 3 H + + HCO 3 - Hb - + H + HHb TISSUES: DEOXY-Hb binds H + more readily (weaker acid)  ↑ amount of chemically bound CO 2 ? physiological values in arterial and venous blood total CO 2 content (mmol/l) Hb.NH.COO - 1 Hb - + H + HHb 2 LUNGS: H + is released from OXY-Hb  ↓ amount of chemically bound CO 2 DEOXY-Hb

29. PROCESSES UNDERLYING TRANSPORT O 2 AND CO 2 FACILITATE EACH OTHER 17 BOHR´s AND HALDANE´s EFFECTS uptake of CO 2 by blood release of O 2 from Hb TISSUES binding of O 2 to Hb release of CO 2 from blood LUNGS OCCUR SIMULTANEOUSLY IN RED BLOOD CELLS

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