Post on 10-Aug-2018
transcript
1
Oxygen Uptake – Transport - Delivery
Lessenreeks co’s 2017-2018 Zuurstoftransport
Professor Dr. Steffen Rex Department of Anesthesiology University Hospitals Leuven Department of Cardiovascular Sciences KU Leuven steffen.rex@uzleuven.be
Oxygen Uptake – Transport - Delivery
Learning objectives
§ Oxygen cascade § PiO2 § PAO2 § Diffusion § ∆AaPO2: Shunt § Oxygen transport § Oxygen content § Oxygen delivery § Oxygen consumption § Therapeutic principles
2
Oxygen Uptake – Transport - Delivery
Critical dependency on oxygen
Principal stores of body oxygen Breathing air (ml) Breathing 100% O2 (ml)
In the lungs (FRC) 450 3000
In the blood 850 950
Dissolved in tissue fluids 50 ?100
Myoglobin ?200 ?200
Total 1550 4250
Oxygen consumption = 3-4 ml/kg/min = 300 ml/min
Oxygen Uptake – Transport - Delivery
Oxygen cascade
3
Oxygen Uptake – Transport - Delivery
Oxygen cascade: Decrease of PO2 from air to mitochondria 159 mmHg
4-23 mmHg
Oxygen Uptake – Transport - Delivery
Oxygen cascade
159 mmHg
4-23 mmHg
4
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2)
mmHgPiO 1597602094.02 =∗=
Dalton‘s law:
mmHgPiO 7607600.12 =∗=
STPD = Standard Temperature Pressure Dry
(0°C, dry)
Pigas = Figas * Ptotal
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2)
à concentration of atmospheric oxygen: 20.94% (159 mmHg)(dry gas!) à Humidification of gas during passage through the respiratory tract à Dilution of oxygen by added water vapour
( ) )37(149477602094.02 CmmHgPiO °=−∗=BTPS = Body Temperature Pressure Saturated
PiO2 = FiO2 (dry) * (Pb-PH2O)
5
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2) How to increase FiO2
~ 40 %
~ 40-60 %
~ 60-80 %
100 %
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2): The importance of PB
à Constant concentration of atmospheric oxygen: 20.94%
à Decrease of barometric pressure with altitude
( )OHB PPdryFiOPiO2
)(22 −∗=
6
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2) The importance of PB
Armstrong‘s limit: PH20 (37°C) = 47mmHg = PB
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2) The importance of PB
Beall C Two routes to functional adaptation: Tibetan and Andean high-altitude natives. PNAS May 15, 2007 vol. 104 suppl. 1 8655–8660
Oxygen cascade at high altitude
7
Oxygen Uptake – Transport - Delivery
Pressure of inspired oxygen (PiO2) Oxygen cascade at high altitude
Grocott M. et al. Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest. N Engl J Med 2009;360:140-9
Oxygen Uptake – Transport - Delivery
Oxygen cascade
159 mmHg
4-23 mmHg
8
Oxygen Uptake – Transport - Delivery
Pressure of alveolar oxygen (PAO2) Alveolar air equation
PAO2 ≈ PiO2 – PACO2 PAO2 ≈ PiO2 – PaCO2/RQ
≈ 149 – 40/0.9 ≈ 105 mmHg ≈ 14 % (of 760mmHg)
⎟⎟⎠
⎞⎜⎜⎝
⎛ −−=
2
22222 PeCO
PeOPiOPaCOPiOPAO
Hypoventilation: can cause hypoxia Hyperventilation: compensatory response to high altitude
PIO2
Oxygen Uptake – Transport - Delivery
Pressure of alveolar oxygen (PAO2)
VO2
To maintain PAO2 ñ VO2 à ñ Alv. Vent. Constant Alv. Vent. ñ VO2 à ò PAO2
PIO2
9
Oxygen Uptake – Transport - Delivery
Diffusion
Oxygen Uptake – Transport - Delivery
Diffusion Barriers
Gas space within the alveolus: uniform distribution of O2, N2, CO2 àNo barrier Alveolar lining fluid: thin Tissue barrier: Alveolar epithelium: 0.2µm Interstitial space: 0.1µm Endothelium: 0.2µm Plasma layer Diffusion into and within the red blood cells Uptake of oxygen by hemoglobin (time-dependent reaction)
10
Oxygen Uptake – Transport - Delivery
Diffusion Fick‘s law
PcapO2 PAO2
Wall thickness χ
ΔnΔt
= −D∗A∗ Δcχ
D = Diffusion coefficient
Destruction of alveoli in emphysema
Edema Fibrosis
Hypoxia
Oxygen Uptake – Transport - Delivery
Diffusion capacity: Calculation
89.5)(067.0)(9.10 −∗−∗= yearsagemheightDLCO
30 years, 1.78m à 34.4 ml/min/mmHg
89.0)(054.0)(1.7 −∗−∗= yearsagemheightDLCO
• Lung volume • Posture (Supine > standing/sitting) • Age • Sex (Men > Women) • White > Black Race
11
Oxygen Uptake – Transport - Delivery
Alveolar/arterial PO2 difference
PAO2 = 105 mmHg
PaO2 = 102 – 0.33 * age (mmHg)
∆AaPO2 = 15-35 mmHg
Oxygen Uptake – Transport - Delivery
Alveolar/arterial PO2 difference
Healthy Shunt Dead Space
12
Oxygen Uptake – Transport - Delivery
Alveolar/arterial PO2 difference
SHUNT Anatomical (extrapulmonary) Thebesian veins (0.3% of CO) Bronchial veins (1% of CO) Congenital heart disease Intrapulmonary (V/Q < 1) Atelectasis Pneumonia ARDS
Oxygen Uptake – Transport - Delivery
Venous admixture Shunt: Calculation
scT QQQ !!! +=
222 OvCQCcOQCaOQ scT ∗+∗=∗ !!!
22
22
OvCCcOCaOCcO
T
s
−
−=!
!
13
Oxygen Uptake – Transport - Delivery
Venous admixture Effects on blood gases
PO2 Even marked effects on PaO2 à Minor effects on caO2 Minor changes in caO2 à marked effects on PaO2
PCO2 Nearly linear correlation between PaCO2 and caCO2
Oxygen Uptake – Transport - Delivery
Venous admixture The iso-shunt diagram
With increasing shunt (≥ 30%), hypoxia can no longer be treated with added inspired oxygen
14
Oxygen Uptake – Transport - Delivery
Oxygen cascade
Oxygen Uptake – Transport - Delivery
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 O2 / ml blood / mmHg à PO2 100 mmHg 0.3 ml O2 / 100 ml
15
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Chemically bound: Hemoglobin
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Chemically bound: Hemoglobin
16
Oxygen Uptake – Transport - Delivery
Venous point
Arterial point
Oxygen transport within the blood: Oxyhemoglobin dissociation curve Sigmoidal shape:
Binding of the 1st O2 molecule increases affinity of hemoglobin for the O2 next molecule
Advantages: 1) Decreases in PaO2 are tolerated
over a relatively wide range 2) High affinity of hemoglobin for O2:
a. Maximal saturation is achieved at „normal“ PaO2
b. O2-uptake in the lungs is facilitated
3) Low affinity of hemoglobin for O2: à O2-delivery is facilitated at low PaO2
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Position of the HbO2 dissociation curve P50 =
PaO2 that achieves a SaO2 of 50% (27mmHg) Right shift: P50 > 27 mmHg Less affinity of Hb for O2 Facilitated O2-release to periphery Left shift: P50 < 27mmHg Higher affinity of Hb for O2 Impaired O2-release into periphery
17
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Position of the HbO2 dissociation curve
Right shift: ò pH ñ pCO2 ñ Temp. ñ 2,3-DPG Left shift: ñ pH ò pCO2 ò Temp. ò 2,3-DPG
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Bohr effect
Affinity of Hb to O2 is inversely related to acidity and CO2-concentration Lungs: High pH, low CO2 à High affinity à Facilitated O2-uptake
Peripheral tissues: Low pH, high CO2 à Low affinity à Facilitated O2-release Hsia C. et al.
RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998
↑pCO2
↓pCO2
18
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Coupled O2 and CO2 transport
Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998
MECHANISMS OF DISEASE
Volume 338 Number 4
!
241
ity of oxygen is diminished (as in hypoxia or anemia)or the flux through glycolysis is stimulated (as in al-kalosis). The 2,3-bisphosphoglycerate concentrationis reduced in aging red cells and under conditions ofhyperoxia or inhibition of glycolysis (by acidosis orhypophosphatemia). Other organophosphates andanions, such as chloride, also compete with 2,3-bis-phosphoglycerate for binding sites on hemoglobin.Hence, their presence can reduce the regulatory ef-fect of 2,3-bisphosphoglycerate on oxygen affinity.
10
Effect of Temperature
As the body temperature increases, the affinity ofhemoglobin for oxygen decreases, raising the P
50
and facilitating oxygen release. This feature is partic-ularly beneficial during prolonged heavy exercise.Temperature effects can cause errors in the interpre-tation of blood gas values, because in clinical labo-ratories the oxygen tension is usually measured at37°C, not at the temperature in vivo. Hence, thetrue in vivo oxygen tension may be underestimatedin hyperthermia and overestimated in hypothermia,particularly when the oxygen tension lies along thesteep portion of the dissociation curve.
6
For exam-ple, in a febrile patient (temperature, 41°C) with ameasured arterial oxygen tension of 60 mm Hg (at
37°C), the true in vivo oxygen tension is approxi-mately 20 percent higher (72 mm Hg). The samemeasurement in a patient with hypothermia (tem-perature, 33°C) corresponds to an in vivo oxygentension of approximately 48 mm Hg. The carbon di-oxide tension is similarly underestimated in hyper-thermia and overestimated in hypothermia. Cor-rection for these temperature effects permits theaccurate calculation of the alveolar–arterial oxygentension gradient. Since the pH of neutrality varieswith temperature, no correction for pH is necessary.These corrections are available in nomograms orcomputer algorithms.
5
Binding of Nitric Oxide
Hemoglobin scavenges nitric oxide through thehigh-affinity ferrous binding sites on heme (with anaffinity for nitric oxide 8000 times their affinity foroxygen). Recently a second binding site was report-ed at the
b
93 cysteine residue on the globin chain,where nitric oxide binds in the form of
S
-nitrosothi-ol.
20
The transfer of nitric oxide from
S
-nitrosothiolto hemoglobin is allosterically regulated and func-tionally linked to the binding of oxygen to hemoglo-bin. As hemoglobin binds oxygen in the lungs, itsbinding affinity for
S
-nitrosothiol is increased. As
Figure 2.
Coupled Oxygen and Carbon Dioxide Transport within the Red Cell.In the peripheral tissues, the uptake of carbon dioxide by red cells and chemical reactions with hemo-globin facilitate the release of oxygen from hemoglobin. Hb denotes hemoglobin.
Red Cell Tissue
CO2
CO2 ! H2O
H2CO3
CO2Hb–O2
Hb–O2 Hb–H!
H!
H!!
HCO3" ! H!
Carbonicanhydrase
Carbamino-Hb
O2
O2
CI"
The New England Journal of Medicine Downloaded from nejm.org at KU LEUVEN BIOMEDICAL LIBRARY on January 12, 2012. For personal use only. No other uses without permission.
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
80%
10%
10%: CO2 in physical solution
Oxygen Uptake – Transport - Delivery
Carbon dioxide transport within the blood: Haldane effect
Affinity of Hb to CO2 is inversely related to O2-concentration Lungs: High O2 à Low affinity for CO2 à Facilitated CO2-release
Peripheral tissues: Low O2 à High affinity for CO2 à Facilitated CO2-uptake
Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998
19
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood: Red-Cell 2,3-Disphosphoglycerate (DPG)
In normal cells: negative feedback inhibition of DPG-synthase by 2,3-DPG In red cells: 2,3-DPG is sequestered by Hbdeoxy à no feedback inhibition In normal red cells: marginal significance Chronic anemia/hypoxia: ñ 2,3-DPG Transfusion: Inhibition of glycolysis by hypothermia during storage à ò DPG-production à Left-shift of Hb-O2-dissociation curve
Hsia C. et al. RESPIRATORY FUNCTION OF HEMOGLOBIN. N Engl J Med 1998
Rapoport-Luebering-shunt
Glycolysis
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Dissociation curves
Adult Hb
Fetal Hb
Fetal Hb: Leftward shift à Facilitated O2-uptake at low PO2 in placenta Myoglobin: O2-release only at PO2 <15-30mmHg (at exercise) Carboxyhemoglobin: Extremely high affinity of Hb for CO
20
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Oxygen saturation
%100982
22
−=
+=
HbdeoxyHbOHbOSpO
Dual wave oxymeter
%98962
22
−=
++++=
SulfHbCOHbMetHbHbdeoxyHbOHbOSaO
Multiwave oxymeter
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Oxygen-binding capacity of hemoglobin
Hüfner‘s constant 1 mol Hb ≈ 4 mol O2 1 mol O2 ≈ 22.4 l 1 mol Hb ≈ 89.6 l 1 mol Hb ≈ 64500 g 1 g Hb ≈ 1.31 ml O2
≈ 1.34 ≈ 1.39
Physically dissolved
Chemically bound
21
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Oxygen content
CaO2 = dissolved O2 + chemically bound O2 CaO2 = α * PaO2 + (SaO2 * [Hb] * 1.31) ml/dl ml/dl * mmHg + (%/100) * g/dl * ml/g
= 0.003 * 100 + (0.98 * 15 *1,31) = 0.3 + 19.26
CaO2 ≈ 20 ml/dl CvO2 = α * PvO2 + (SvO2 * [Hb] * 1.31)
= 0.003 * 40 + (0.75 * 15 *1,31) = 0.12 + 14.74 ≈ 15 ml/dl
avDO2 = 5 ml/dl O2ER = (avDO2/CaO2) * 100 = 25%
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Oxygen content
Training at high altitude
McLellan S.A. et al. Oxygen delivery and hemoglobin. Contin Educ Anaesth Crit Care Pain 2004
22
Oxygen Uptake – Transport - Delivery
When oxygen is too low….
Hypoxia = ò PaO2 Hypoxygenation = ò SpO2 Hypoxemia = ò caO2 Ischemia = ò No blood flow
Hypoxic
Anemic
CaO2 = α * PaO2 + (SaO2 * Hb * 1.31)
Hypoxemia
Toxic: HbCO, Met-Hb Tolerance: Anemic (Right-shift) > Hypoxic > Toxic (Left-shift)
Oxygen Uptake – Transport - Delivery
Oxygen transport within the blood Oxygen delivery DO2 = Cardiac output * Arterial oxygen content ml/min l/min * (ml/dl * 10)
= 5 + (20 * 10) DO2 ≈ 1000 ml/min VO2 = Cardiac output * avDO2
= 5 * (5 * 10) ≈ 250 ml/min
O2ER = VO2 / DO2
= 25%
23
Oxygen Uptake – Transport - Delivery
When oxygen delivery is too low….
Sc(v)O2: 17% 37% 57% 47%
77%
67%
Increase in oxygen extraction Decrease in central (mixed) venous oxygen saturation
Oxygen Uptake – Transport - Delivery
Oxygen cascade: The last step: Diffusion into the cell
Leach R. et al. ABC of oxygen. Oxygen transport—2. Tissue hypoxia BMJ 1998;317:1370-3
24
Oxygen Uptake – Transport - Delivery
Summary of oxygen cascade
Treacher D.F. et al. ABC of oxygen. Oxygen transport—1. Basic principles BMJ 1998;317:1302-6
1 kPa = 7,5 mmHg
Oxygen Uptake – Transport - Delivery
What can we do to improve DO2?
Rampal T et al. Using oxygen delivery targets to optimize resuscitation in critically ill patients.
Current Opinion in Critical Care 2010,16:244–249
25
Oxygen Uptake – Transport - Delivery
What you learnt in this lecture...
§ Oxygen cascade § PiO2 § PAO2 § Diffusion § ∆AaPO2: Shunt § Oxygen transport § Oxygen content § Oxygen delivery § Oxygen consumption § Therapuetic principles
Oxygen Uptake – Transport - Delivery
Suggested readings (and sources of different figures)