What you will learn in this lecture... Lessenreeks co s 014-015 Fysiologie van de ademhaling - gasuitwisseling Professor Dr. Steffen Rex Department of Anesthesiology University Hospitals Leuven Department of Cardiovascular Sciences KU Leuven steffen.rex@uzleuven.be! Oxygen cascade! PiO! PAO! Diffusion! AaPO : Shunt! Oxygen transport! Oxygen content! Oxygen delivery! Oxygen consumption! Therapeutic principles Critical dependency on oxygen Oxygen cascade Principal stores of body oxygen Breathing air (ml) Breathing 100% O (ml) In the lungs (FRC) 450 3000 In the blood 850 950 Dissolved in tissue fluids 50?100 Myoglobin?00?00 Total 1550 450 Oxygen consumption = 3-4 ml/kg/min = 300 ml/min 1
Oxygen cascade: Decrease of PO from air to mitochondria 159 mmhg Oxygen cascade 159 mmhg 4-3 mmhg 4-3 mmhg Pressure of inspired oxygen (PiO ) Pressure of inspired oxygen (PiO ) Dalton s law: Pi gas = Fi gas * P total PiO = 0.094 760 159mmHg = PiO = 1.0 760 760mmHg = (0 C, dry) STPD = Standard Temperature Pressure Dry " concentration of atmospheric oxygen: 0.94% (159 mmhg)(dry gas!) " Humidification of gas during passage through the respiratory tract " Dilution of oxygen by added water vapour PiO = FiO (dry) * (P b -P HO ) ( 760 47) = 149mmHg(37 ) PiO = 0.094 C BTPS = Body Temperature Pressure Saturated
Pressure of inspired oxygen (PiO ) How to increase FiO Pressure of inspired oxygen (PiO ): The importance of P B 100 % " Constant concentration of atmospheric oxygen: 0.94% (159 mmhg) ~ 40 % " Decrease of barometric pressure with altitude ~ 40-60 % ( ) PiO = FiO( dry) P B P H O ~ 60-80 % Pressure of inspired oxygen (PiO ) The importance of P B Pressure of inspired oxygen (PiO ) The importance of P B Oxygen cascade at high altitude Armstrong s limit: P H0 (37 C) = 47mmHg = P B Beall C Two routes to functional adaptation: Tibetan and Andean high-altitude natives. PNAS May 15, 007 vol. 104 suppl. 1 8655 8660 3
Pressure of inspired oxygen (PiO ) Oxygen cascade at high altitude Oxygen cascade 159 mmhg 4-3 mmhg Grocott M. et al. Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest. N Engl J Med 009;360:140-9 Pressure of alveolar oxygen (PAO ) Alveolar air equation Pressure of alveolar oxygen (PAO ) PIO PIO To maintain PAO # VO " # Alv. Vent. Constant Alv. Vent. # VO " $ PAO PAO PiO PACO PAO PiO PaCO /RQ 149 40/0.9 105 mmhg 14 % (of 760mmHg) & PiO # PeO PAO = $! PiO PaCO % PeCO " Hypoventilation: can cause hypoxia Hyperventilation: compensatory response to high altitude VO 4
Diffusion Diffusion Barriers Gas space within the alveolus: uniform distribution of O, N, CO "No barrier Alveolar lining fluid: thin Tissue barrier: Alveolar epithelium: 0.µm Interstitial space: 0.1µm Endothelium: 0.µm Plasma layer Diffusion into and within the red blood cells Uptake of oxygen by hemoglobin (time-dependent reaction) Diffusion Fick s law Diffusion capacity: Calculation DL CO = 10.9 height( m) 0.067 age( years) 5.89 30 years, 1.78m " 34.4 ml/min/mmhg P cap O P A O Destruction of alveoli in emphysema Hypoxia Wall thickness χ AREA Δn Δc = D A Δt Δχ Edema Fibrosis D = Diffusion coefficient DL CO = 7.1 height( m) 0.054 age( years) 0.89 Lung volume Posture (Supine > standing/sitting) Age Sex (Men > Women) White > Black Race 5
Alveolar/arterial PO difference Alveolar/arterial PO difference PAO = 105 mmhg AaPO = 15-35 mmhg PaO = 10 0.33 * age (mmhg) Shunt Healthy Dead Space Alveolar/arterial PO difference SHUNT Anatomical (extrapulmonary) Thebesian veins (0.3% of CO) Bronchial veins (1% of CO) Congenital heart disease Intrapulmonary (V/Q < 1) Venous admixture Shunt: Calculation Q! = Q! + Q! T c Q! CaO!! T Q! s Q! T s = Qc CcO + Qs CvO CcO CaO = CcO CvO Atelectasis Pneumonia ARDS 6
Venous admixture Effects on blood gases Venous admixture The iso-shunt diagram PO Minor changes in CaO " Marked effects on PaO PCO Even major changes in CaCO " Minimal effects on PaCO With increasing shunt ( 30%), hypoxia can no longer be treated with added inspired oxygen Oxygen cascade Oxygen transport within the blood: Physically dissolved Henry s law c = α * p c = concentration α = Bunsen s solubility coefficient p = partial pressure α = 0.000031 ml O / ml blood / mmhg " PO 100 mmhg 0.3 ml O / 100 ml 7
Oxygen transport within the blood: Chemically bound: Hemoglobin Oxygen transport within the blood: Chemically bound: Hemoglobin Oxygen transport within the blood: Oxyhemoglobin dissociation curve Sigmoidal shape: Binding of the 1 st O molecule increases affinity of hemoglobin for the O next molecule Oxygen transport within the blood: Position of the HbO dissociation curve P50 = PaO that achieves a SaO of 50% (7mmHg) Arterial point Right shift: P50 > 7 mmhg Advantages: 1) Decreases in PaO are tolerated over a relatively wide range ) High affinity of hemoglobin for O : a. Maximal saturation is achieved at normal PaO b. O -uptake in the lungs is facilitated 3) Low affinity of hemoglobin for O : " O -delivery is facilitated at low PaO Venous point Less affinity of Hb for O Facilitated O -release to periphery Left shift: P50 < 7mmHg Higher affinity of Hb for O Impaired O -release into periphery 8
Oxygen transport within the blood: Position of the HbO dissociation curve Oxygen transport within the blood: Bohr effect Right shift: $ ph # pco # Temp. #,3-DPG Left shift: # ph $ pco $ Temp. $,3-DPG Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998 pco pco Affinity of Hb to O is inversely related to acidity and CO - concentration Lungs: High ph, low CO " High affinity " Facilitated O -uptake Peripheral tissues: Low ph, high CO " Low affinity " Facilitated O -release Carbon dioxide transport within the blood: Haldane effect Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998 Affinity of Hb to CO is inversely related to O -concentration Lungs: High O " Low affinity for CO " Facilitated CO -release Peripheral tissues: Low O " High affinity for CO " Facilitated CO -uptake Oxygen transport within the blood: Red-Cell,3-Disphosphoglycerate (DPG) Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998 Glycolysis Rapoport-Luebering-shunt In normal cells: negative feedback inhibition of DPG-synthase by,3-dpg In red cells:,3-dpg is sequestered by Hb deoxy " no feedback inhibition In normal red cells: marginal significance Transfusion: Inhibition of glycolysis by hypothermia during storage " $ DPG-production " Left-shift of Hb-O -dissociation curve 9
Oxygen transport within the blood Dissociation curves Oxygen transport within the blood Oxygen saturation Adult Hb Fetal Hb Fetal Hb: Leftward shift " Facilitated O -uptake at low PO in placenta Myoglobin: O -release only at PO <15-30mmHg (at exercise) Carboxyhemoglobin: Extremely high affinity of Hb for CO HbO SpO = HbO + Hbdeoxy = 98 100% = 96 98% SaO = HbO Dual wave oxymeter HbO + Hbdeoxy + MetHb + COHb + SulfHb Multiwave oxymeter Oxygen transport within the blood Oxygen-binding capacity of hemoglobin Oxygen transport within the blood Oxygen content Hüfner s constant 1 mol Hb 4 mol O 1 mol O.4 l 1 mol Hb 89.6 l 1 mol Hb 64500 g 1 g Hb 1.31 ml O 1.34 1.39 Physically dissolved Chemically bound CaO = dissolved O + chemically bound O CaO = α * PaO + (SaO * [Hb] * 1.31) ml/dl ml/dl * mmhg + (%/100) * g/dl * ml/g = 0.003 * 100 + (0.98 * 15 *1,31) = 0.3 + 19.6 CaO 0 ml/dl CvO = α * PvO + (SvO * [Hb] * 1.31) = 0.003 * 40 + (0.75 * 15 *1,31) = 0.1 + 14.74 15 ml/dl avdo = 5 ml/dl O ER = (avdo /CaO ) * 100 = 5% 10
Oxygen transport within the blood Oxygen content When oxygen is too low. Hypoxia = $ PaO Hypoxygenation = $ SpO Hypoxemia = $ cao Ischemia = $ No blood flow Training at high altitude Hypoxemia Hypoxic CaO = α * PaO + (SaO * Hb * 1.31) McLellan S.A. et al. Oxygen delivery and hemoglobin. Contin Educ Anaesth Crit Care Pain 004 Anemic Toxic: HbCO, Met-Hb Tolerance: Anemic (Right-shift) > Hypoxic > Toxic (Left-shift) Oxygen transport within the blood Oxygen delivery DO = Cardiac output * Arterial oxygen content When oxygen delivery is too low. ml/min l/min * (ml/dl * 10) = 5 + (0 * 10) S c(v) O : 17% 37% 47% 57% 67% DO 1000 ml/min VO = Cardiac output * avdo = 5 * (5 * 10) 77% Increase in oxygen extraction Decrease in central (mixed) venous oxygen saturation 50 ml/min O ER = VO / DO = 5% 11
Oxygen cascade: The last step: Diffusion into the cell Summary of oxygen cascade Leach R. et al. ABC of oxygen. Oxygen transport. Tissue hypoxia BMJ 1998;317:1370-3 Treacher D.F. et al. ABC of oxygen. Oxygen transport 1. Basic principles BMJ 1998;317:130-6 1 kpa = 7,5 mmhg What can we do to improve DO? What you learnt in this lecture...! Oxygen cascade! PiO! PAO! Diffusion! AaPO : Shunt! Oxygen transport! Oxygen content! Oxygen delivery! Oxygen consumption! Therapuetic principles Rampal T et al. Using oxygen delivery targets to optimize resuscitation in critically ill patients. Current Opinion in Critical Care 010,16:44 49 1
Suggested readings (and sources of different figures) Thank you for your time and attention 13