Fysiologie van de ademhaling - gasuitwisseling

Lessenreeks co’s 2012-2013
Fysiologie van de ademhaling gasuitwisseling
Professor Dr. Steffen Rex
Department of Anesthesiology
University Hospitals of the KU Leuven
[email protected]
Fysiologie van de gasuitwisseling
What you will learn today
!  Oxygen cascade
!  PiO2
!  PAO2
!  Diffusion
!  !AaPO2: Shunt
!  Oxygen transport / content / delivery
!  Pulse oximetry
!  Therapeutic principles to improve oxygenation
!  CO2-transport
!  Capnography
Fysiologie van de gasuitwisseling
1
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
Fysiologie van de gasuitwisseling
Oxygen cascade
Fysiologie van de gasuitwisseling
2
Oxygen cascade:
Decrease of PO2 from air to mitochondria
159 mmHg
4-23 mmHg
Fysiologie van de gasuitwisseling
Pressure of inspired oxygen (PiO2)
Dalton‘s law:
Pi gas = Fi gas ! Ptotal
PiO2 = 0.2094! 760 = 159mmHg
(0°C, dry)
PiO2 = 1.0 ! 760 = 760mmHg
STPD = Standard Temperature Pressure Dry
Fysiologie van de gasuitwisseling
3
Pressure of inspired oxygen (PiO2)
How to increase FiO2
100 %
~ 40 %
~ 40-60 %
~ 60-80 %
Fysiologie van de gasuitwisseling
Pressure of inspired oxygen (PiO2)
! Concentration of atmospheric oxygen: 20.94% (159 mmHg) (dry gas!)
! Humidification of gas during passage through the respiratory tract
! Dilution of oxygen by added water vapour
(
PiO2 = FiO2 (dry ) " PB ! PH 2O
)
PiO2 = 0.2094" (760 ! 47) = 149mmHg(37°C)
BTPS = Body Temperature Pressure Saturated
Fysiologie van de gasuitwisseling
4
Pressure of inspired oxygen (PiO2)
! Constant concentration of atmospheric oxygen: 20.94% (159 mmHg)
! Decrease of barometric pressure
with altitude
(
PiO2 = FiO2 (dry ) " PB ! PH 2O
)
Fysiologie van de gasuitwisseling
Pressure of inspired oxygen (PiO2)
Fysiologie van de gasuitwisseling
5
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
Fysiologie van de gasuitwisseling
Oxygen cascade
159 mmHg
4-23 mmHg
Fysiologie van de gasuitwisseling
6
Pressure of alveolar oxygen (PAO2)
Alveolar air equation
PAO2
" PiO2 – PaCO2
PAO2 " PiO2 – PaCO2/RQ
" 149 – 40/0.9
" 105 mmHg
" 14
% (of 760mmHg)
& PiO2 ' PeO2 #
!!
PAO2 = PiO2 ' PaCO2 $$
% PeCO2 "
Hypoventilation:
can cause hypoxia
Hyperventilation:
compensatory response to high altitude
Fysiologie van de gasuitwisseling
Diffusion
Pulmonary
capillary
Fysiologie van de gasuitwisseling
7
Diffusion
Barriers
Gas space within the alveolus:
uniform distribution of O2, N2, CO2
!No barrier
Alveolar lining fluid: thin
Tissue barrier:
Alveolar epithelium: 0.2#m
Interstitial space: 0.1#m
Endothelium: 0.2#m
Plasma layer
Diffusion into and within the red blood cells
Uptake of oxygen by hemoglobin
(time-dependent reaction)
Fysiologie van de gasuitwisseling
Diffusion
Fick‘s law
PcapO2
PAO2
Destruction of
alveoli in
emphysema
Hypoxia
Edema
Fibrosis
"n
"c
= $D # A #
"t
"!
Wall thickness $
D = Diffusion coefficient
Fysiologie van de gasuitwisseling
8
Diffusion
Pulmonary edema
Fysiologie van de gasuitwisseling
Diffusion capacity:
Calculation
DLCO = 10.9 " height (m) ! 0.067 " age( years) ! 5.89
30 years, 1.78m ! 34.4 ml/min/mmHg
DLCO = 7.1" height (m) ! 0.054 " age( years) ! 0.89
• Lung volume
• Posture (Supine > standing/sitting)
• Age
• Sex (Men > Women)
• White > Black Race
Fysiologie van de gasuitwisseling
9
Alveolar/arterial PO2 difference
PAO2 = 105 mmHg
!AaPO2 = 15-35 mmHg
PaO2 = 102 – 0.33 * age
(mmHg)
Fysiologie van de gasuitwisseling
Alveolar/arterial PO2 difference
Shunt
Healthy
Dead Space
Fysiologie van de gasuitwisseling
10
Alveolar/arterial PO2 difference
SHUNT
Anatomical (extrapulmonary)
Thebesian veins (0.3% of CO)
Bronchial veins (1% of CO)
Congenital heart disease
Intrapulmonary (Va/Q < 1)
Atelectasis
Pneumonia
ALI
Pulmonary collapse
Fysiologie van de gasuitwisseling
Venous admixture
Shunt: Calculation
Q! T = Q! c + Q! s
Q! T ! CaO2 = Q! c ! CcO2 + Q! s ! Cv O2
Q! s CcO2 ! CaO2
=
Q! T CcO2 ! Cv O2
Fysiologie van de gasuitwisseling
11
Venous admixture
The iso-shunt diagram
With increasing shunt (% 30%),
hypoxemia can no longer be
treated with added inspired
oxygen
Fysiologie van de gasuitwisseling
Venous admixture
Summary
Fysiologie van de gasuitwisseling
12
Oxygen cascade
Fysiologie van de gasuitwisseling
Oxygen transport within the blood:
Physically dissolved
Henry‘s law
c=&*p
c = concentration
& = Bunsen solubility coefficient
p = partial pressure
& = 0.000031 ml O2 / ml blood / mmHg
! PO2 100 mmHg
0.3 ml O2 / 100 ml
Fysiologie van de gasuitwisseling
13
Oxygen transport within the blood:
Chemically bound: Hemoglobin
Fysiologie van de gasuitwisseling
Oxygen transport within the blood:
Chemically bound: Hemoglobin
Fysiologie van de gasuitwisseling
14
Oxygen transport within the blood:
Oxyhemoglobin dissociation curve
Sigmoidal shape:
Binding of the 1st O2 molecule increases affinity of
hemoglobin for the next O2 molecule
Lung
Venous point
Advantages:
1)  Decreases in PO2 are tolerated
over a relatively wide range
2)  Maximal saturation is achieved at
„normal“ PO2
Tis
sue
Ca
pill
ary
Arterial point
3)  O2-release is facilitated at low PO2
Fysiologie van de gasuitwisseling
Oxygen transport within the blood:
Position of the HbO2 dissociation curve
P50 =
PO2 that achieves a SpO2 of
50% (27mmHg)
Right shift:
"PO2 = > 27 mmHg
Less affinity of Hb for O2
Facilitated O2-release into
periphery
Left shift:
#PO2 = < 27mmHg
Higher affinity of Hb for O2
Impaired O2-release into
periphery
Fysiologie van de gasuitwisseling
15
Oxygen transport within the blood:
Position of the HbO2 dissociation curve
Right shift:
# pH
" pCO2
" Temp.
" 2,3-DPG
Left shift:
" pH
# pCO2
# Temp.
# 2,3-DPG
Fysiologie van de gasuitwisseling
Oxygen transport within the blood:
Bohr effect
"pCO2
Affinity of Hb to O2 is
inversely related to
acidity and CO2concentration
!pCO2
Lungs:
High pH, low CO2
" High affinity
" Facilitated O2-uptake
Peripheral tissues:
Hsia C. et al.
RESPIRATORY FUNCTION OF HEMOGLOBIN.
N Engl J Med 1998
Low pH, high CO2
" Low affinity
" Facilitated O2-release
Fysiologie van de gasuitwisseling
16
Oxygen transport within the blood:
Red-Cell 2,3-Disphosphoglycerate (DPG)
Glycolysis
In normal cells:
negative feedback inhibition of DPGsynthase by 2,3-DPG
In red cells:
2,3-DPG is sequestered by Hbdeoxy ! no
feedback inhibition
In normal red cells: marginal significance
Rapoport-Luebering-shunt
Transfusion:
Inhibition of glycolysis by hypothermia
during storage ! # DPG-production ! Leftshift of Hb-O2-dissociation curve
Hsia C. et al.
RESPIRATORY FUNCTION OF HEMOGLOBIN.
N Engl J Med 1998
Fysiologie van de gasuitwisseling
Oxygen transport within the blood
Dissociation curves
Fetal Hb:
Leftward shift !
Facilitated O2-uptake at low PO2 in
placenta
Adult Hb
Myoglobin:
Fetal Hb
O2-release only at PO2 <15-30mmHg
(at exercise)
Carboxyhemoglobin:
Extremely high affinity of Hb for CO
Fysiologie van de gasuitwisseling
17
Oxygen transport within the blood
Oxygen saturation
SpO2 =
HbO2
HbO2 + Hbdeoxy
Dual wave oxymeter
= 98 ! 100%
SaO2 =
HbO2
HbO2 + Hbdeoxy + MetHb + COHb + SulfHb
= 96 ! 98%
Multiwave oxymeter
Fysiologie van de gasuitwisseling
Oxygen transport within the blood
Oxygen saturation: How to measure?
Pulse oximetry
Fysiologie van de gasuitwisseling
18
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
!  Plethysmography
•  Pulsatile flow: discrimination art/ven bloed en weefsel
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
!  Spectrophotometry
•  Principle: light extinction is dependent upon concentration of light
absorbing substance (Lambert-Beer’s law)
•  OxyHb primarily absorbs IR light (940 nm)
•  DesoxyHb primarily absorbs red light (660nm)
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
19
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
!  Spectrophotometry
Calculation of absorption ratio 660/940 nm
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
Limitations:
!  Methemoglobin (metHb)
•  Absorbs R en IR light 1:1 => sat 85%
•  Falsely low values
!  Carboxyhemoglobin (HbCO)
•  Imitates absorption characteristics of HbO2
•  Falsely high values
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
20
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
Absorption characteristics
falsely account for a low sat
in the patient with Hgb-Met
Hgb-CO & Hgb-O2 have similar
absorbance at 666nm so
Hgb-CO will be falsely interpreted
as Hgb-O2 (high sat)
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
Oxygen transport within the blood
Oxygen saturation: Pulse oximetry
!  Accuracy
•  <2% bias at SO2 > 90%
•  Saturation < 80% " bias # 5%
!  Limitations:
Oxygen/CO
Fysiologie
van de
– Transport
gasuitwisseling
- Delivery
2 Uptake
21
Oxygen transport within the blood
Oxygen-combining capacity of hemoglobin
Hüfner‘s constant
Chemically
bound
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 "
"
"
Physically
dissolved
1.31 ml O2
1.34
1.39
Fysiologie van de gasuitwisseling
Oxygen transport within the blood
Oxygen content
CaO2 = physically diss. O2 + chemically bound O2
CaO2
ml/dl
CaO2
CvO2
= & * PO2
+ (SaO2 * [Hb] * 1.31)
ml/dl * mmHg
+ (%/100) * g/dl * ml/g
= 0.003 * 100
= 0.3
" 20 ml/dl
+ (0.98 * 15 *1,31)
+ 19.26
= & * PO2
= 0.003 * 40
= 0.12
" 15 ml/dl
+ (SvO2 * [Hb] * 1.31)
+ (0.75 * 15 *1,31)
+ 14.74
avDO2 = 5 ml/dl
O2ER = 25%
Fysiologie van de gasuitwisseling
22
Oxygen transport within the blood
Oxygen content
Training at high altitude
Fysiologie van de gasuitwisseling
When oxygen is too low….
Hypoxia
Hypoxygenation
Hypoxemia
Ischemia
Hypoxemia
= # PaO2
= # SpO2
= # CaO2
= # No blood flow
Hypoxic
CaO2 = & * PaO2 + (SaO2 * Hb * 1.31)
Anemic
Toxic:
HbCO, Met-Hb
Tolerance: Anemic (Right-shift) > Hypoxic > Toxic (Left-shift)
Fysiologie van de gasuitwisseling
23
Oxygen transport within the blood
Oxygen delivery
DO2
= Cardiac output
ml/min
* Arterial oxygen content
l/min
=5
* (ml/dl * 10)
+ (20 * 10)
DO2
" 1000 ml/min
VO2
= Cardiac output
=5
* avDO2
* (5 * 10)
" 250 ml/min
O2ER = VO2 / DO2
= 25%
Fysiologie van de gasuitwisseling
When oxygen delivery is too low….
Sc(v)O2:
27%
37%
47%
57%
67%
77%
Increase in oxygen extraction
Decrease in central (mixed) venous oxygen saturation
Fysiologie van de gasuitwisseling
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Oxygen cascade:
The last step: Diffusion into cell
Leach R. et al.
ABC of oxygen. Oxygen transport—2. Tissue hypoxia
BMJ 1998;317:1370-3
Fysiologie van de gasuitwisseling
Summary of oxygen cascade
Fysiologie van de gasuitwisseling
25
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
Fysiologie van de gasuitwisseling
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
Fysiologie van de gasuitwisseling
26
Carbon Dioxide
•  Volatile waste product of cellular metabolism
• 
• 
• 
• 
CO2 production averages 200 ml/min in resting adult
During exercise this amount may increase six-fold
Tissue PtCO2 is 50 mmHg
Diffuses into systemic capillaries with lower PCO2 levels
Fysiologie van de gasuitwisseling
Carbon Dioxide Transport
(I) Dissolved in plasma (7%)
•  20x more soluble in plasma than O2
•  Solubility coefficient: 0,0007 ml/mmHg/ml
•  2,5 ml CO2 in 100 ml arterial blood
(II) Diffusion into erythrocyte (93%)
a)  Binding to hemoglobin (23%)
! carbaminohemoglobin
buffered by reduced hemoglobine
Fysiologie van de gasuitwisseling
27
Carbon Dioxide Transport
(II) Diffusion into erythrocyte (93%)
b) Reacting to carbonic acid (70%)
buffered by reduced hemoglobine
Diffusion into plasma
Exchange for Cl- -ions
HAMBURGER SHIFT
Fysiologie van de gasuitwisseling
Carbon Dioxide Transport
7%
23%
70%
Fysiologie van de gasuitwisseling
28
Carbon dioxide transport within the blood:
Haldane effect
Hbdeoxy is a more
powerful buffer than
HbO2
Affinity of Hb to CO2
is inversely related to
O2-concentration
Lungs:
High O2
" Low affinity for CO2
" Facilitated CO2-release
Peripheral tissues:
Hsia C. et al.
RESPIRATORY FUNCTION OF HEMOGLOBIN.
N Engl J Med 1998
Low O2
" High affinity for CO2
" Facilitated CO2-uptake
Fysiologie van de gasuitwisseling
CO2 Equilibrium Curve
•  Different from HbO2 curve
PO2 = 40mmHg
–  Relationship is linear
–  Venous blood transports more
CO2 than arterial blood
•  CO2 equilibrium is affected by
O2 saturation of Hb
PO2 = 100mmHg
–  Ability to bind CO2 increased in
Hbdeoxy
–  deoxygenated Hb is weaker acid
than oxygenated Hb
•  A-a Pco2 levels not as
effected by V/Q mismatch
–  Diffusing capacity 20x greater
with CO2 than O2
Fysiologie van de gasuitwisseling
29
Carbon Dioxide Delivery
Fysiologie van de gasuitwisseling
Monitoring CO2 Transport & Delivery
Capnography
•  Infrared absorption spectroscopy
•  CO2 absorbs IR-light (wavelength 4,26 $m)
•  Measurement of absorption within exhaled air and in
test gas (known CO2-concentration)
•  Amount of absorption related to CO2-concentration
(Lambert-Beer‘s law)
•  Before measurement: calibration with test gas
Fysiologie van de gasuitwisseling
30
Monitoring CO2 Transport & Delivery
Capnography
• 
Measurement locations
Mainstream
Sidestream
Fysiologie van de gasuitwisseling
Monitoring CO2 Transport & Delivery
Capnography
• 
Accuracy
•  ± 2 mmHg
• 
Limitations
•  Correction for barometric pressure required
•  Obstruction of sample line by water/secretions
•  Interference with CO, N2O, H2O and volatile anesthetics
(do also absorb IR light)
•  Consider sampling time (dependent upon length of sample
line, flow and viscosity of gases)
Fysiologie van de gasuitwisseling
31
Monitoring CO2 Transport & Delivery
Capnogram
Fysiologie van de gasuitwisseling
Monitoring CO2 Transport & Delivery
Capnogram
Fysiologie van de gasuitwisseling
32
Monitoring CO2 Transport & Delivery
Information hidden in capnography
Capnography provides instantaneous information about
! Ventilation:
how effectively is CO2 eliminated by the pulmonary system?
! Perfusion:
how effectively is CO2 transported to the lungs?
! Metabolism:
how effectively is CO2 produced by cellular metabolism?
! Equipment
Fysiologie van de gasuitwisseling
Monitoring CO2 Transport & Delivery
Information hidden in capnography
Fysiologie van de gasuitwisseling
33
What you learnt today
!  Oxygen cascade
!  PiO2
!  PAO2
!  Diffusion
!  !AaPO2: Shunt
!  Oxygen transport / content / delivery
!  Pulse oximetry
!  Therapeutic principles to improve oxygenation
!  CO2-transport
!  Capnography
Fysiologie van de gasuitwisseling
Suggested readings
(and sources of figures)
Fysiologie van de gasuitwisseling
34
Thank you
for your attention
Fysiologie van de gasuitwisseling
Pressure of inspired oxygen (PiO2)
Oxygen cascade at high altitude
Beall C
Two routes to functional adaptation: Tibetan and
Andean high-altitude natives.
PNAS May 15, 2007 vol. 104 suppl. 1 8655–8660
Fysiologie van de gasuitwisseling
35
Pressure of alveolar oxygen (PAO2)
To maintain PAO2
" VO2 ! " Alv. Vent.
Constant Alv. Vent.
" VO2 ! # PAO2
VO2
Fysiologie van de gasuitwisseling
Diffusion:
Transit time
Transit Time
# Transit time
#
# Oxygen uptake
#
" Diffusion gradient
#
"Diffusion capacity
Fysiologie van de gasuitwisseling
36
Venous admixture
Effects on blood gases
PO2
Minor changes in CaO2
" Marked effects on PaO2
" Hypoxemia responds
poorly to added inspired O2
" When 100% O2 is inspired,
the arterial PO2 does not rise
to the expected level
PCO2
Even major changes in CaCO2
! Minimal effects on PaCO2
Fysiologie van de gasuitwisseling
37