Fysiologie van de ademhaling - gasuitwisseling
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1 What you will learn in this lecture... Lessenreeks co s 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) In the blood Dissolved in tissue fluids 50?100 Myoglobin?00?00 Total Oxygen consumption = 3-4 ml/kg/min = 300 ml/min 1
2 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 = mmHg = PiO = mmHg = (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 ) ( ) = 149mmHg(37 ) PiO = C BTPS = Body Temperature Pressure Saturated
3 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 ~ % ( ) PiO = FiO( dry) P B P H O ~ % 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
4 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 / mmhg 14 % (of 760mmHg) & PiO # PeO PAO = $! PiO PaCO % PeCO " Hypoventilation: can cause hypoxia Hyperventilation: compensatory response to high altitude VO 4
5 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) age( years) 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) age( years) 0.89 Lung volume Posture (Supine > standing/sitting) Age Sex (Men > Women) White > Black Race 5
6 Alveolar/arterial PO difference Alveolar/arterial PO difference PAO = 105 mmhg AaPO = mmhg PaO = * 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
7 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 = ml O / ml blood / mmhg " PO 100 mmhg 0.3 ml O / 100 ml 7
8 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
9 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
![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.](/docs-images/83/88352976/images/10-5.jpg "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.")
10 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 = % = 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 g 1 g Hb 1.31 ml O 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 = * (0.98 * 15 *1,31) = CaO 0 ml/dl CvO = α * PvO + (SvO * [Hb] * 1.31) = * 40 + (0.75 * 15 *1,31) = ml/dl avdo = 5 ml/dl O ER = (avdo /CaO ) * 100 = 5% 10
11 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
12 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: Treacher D.F. et al. ABC of oxygen. Oxygen transport 1. Basic principles BMJ 1998;317: 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:
13 Suggested readings (and sources of different figures) Thank you for your time and attention 13
After having worked out this lecture, you will be able to describe the oxygen cascade and to calculate the inspiratory and the alveolar partial
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