Zuurstoftransport - UZ Leuven · Zuurstoftransport Professor Dr. Steffen Rex ... Oxygen cascade at...

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 [email protected]


Learning objectives

§  Oxygen cascade §  PiO2 §  PAO2 §  Diffusion §  ∆AaPO2: Shunt §  Oxygen transport §  Oxygen content §  Oxygen delivery §  Oxygen consumption §  Therapeutic principles

2


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 cascade

3


Oxygen cascade: Decrease of PO2 from air to mitochondria 159 mmHg

4-23 mmHg


Oxygen cascade

159 mmHg

4-23 mmHg

4


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


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


Pressure of inspired oxygen (PiO2) How to increase FiO2

~ 40 %

~ 40-60 %

~ 60-80 %

100 %


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


Pressure of inspired oxygen (PiO2) The importance of PB

Armstrong‘s limit: PH20 (37°C) = 47mmHg = PB


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


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 cascade

159 mmHg

4-23 mmHg

8


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


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


Diffusion


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


Diffusion Fick‘s law

PcapO2 PAO2

Wall thickness χ

ΔnΔt

= −D∗A∗ Δcχ

D = Diffusion coefficient

Destruction of alveoli in emphysema

Edema Fibrosis

Hypoxia


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


Alveolar/arterial PO2 difference

PAO2 = 105 mmHg

PaO2 = 102 – 0.33 * age (mmHg)

∆AaPO2 = 15-35 mmHg



Healthy Shunt Dead Space

12



SHUNT Anatomical (extrapulmonary) Thebesian veins (0.3% of CO) Bronchial veins (1% of CO) Congenital heart disease Intrapulmonary (V/Q < 1) Atelectasis Pneumonia ARDS


Venous admixture Shunt: Calculation

scT QQQ !!! +=

222 OvCQCcOQCaOQ scT ∗+∗=∗ !!!

22

22

OvCCcOCaOCcO

QQ

T

s

−

−=!

!

13


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


Venous admixture The iso-shunt diagram

With increasing shunt (≥ 30%), hypoxia can no longer be treated with added inspired oxygen

14


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 O2 / ml blood / mmHg à PO2 100 mmHg 0.3 ml O2 / 100 ml

15


Oxygen transport within the blood: Chemically bound: Hemoglobin


Oxygen transport within the blood: Chemically bound: Hemoglobin

16


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 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 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 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 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


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


19


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


Rapoport-Luebering-shunt

Glycolysis


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 transport within the blood Oxygen saturation

%100982

22

−=

+=

HbdeoxyHbOHbOSpO

Dual wave oxymeter

%98962

22

−=

++++=

SulfHbCOHbMetHbHbdeoxyHbOHbOSaO

Multiwave oxymeter


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 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 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


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 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


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 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


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


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


What you learnt in this lecture...

§  Oxygen cascade §  PiO2 §  PAO2 §  Diffusion §  ∆AaPO2: Shunt §  Oxygen transport §  Oxygen content §  Oxygen delivery §  Oxygen consumption §  Therapuetic principles


Suggested readings (and sources of different figures)

26


Thank you for your time and attention

Zuurstoftransport - UZ Leuven · Zuurstoftransport Professor Dr. Steffen Rex ... Oxygen cascade at...

Documents

Transcript of Zuurstoftransport - UZ Leuven · Zuurstoftransport Professor Dr. Steffen Rex ... Oxygen cascade at...