Physiology of O2 transport & O2 Dissociation Curve

1. Presented by:
Dr. Md. Zareer Tafadar
Post Graduate Student
Deptt. Of Anaesthesiology &Critical Care
Silchar Medical College & Hospital.
OXYGEN TRANSPORT &
OXYGEN DISSOCIATION
CURVE

2. Components of the Oxygen
Transport System
•Mass Transport from Environment to Alveolar Space
•Diffusion from Alveolar Air to Blood in the Pulmonary Capillary
•Mass Transport from the Pulmonary to the Systemic Capillaries
• Diffusion of Oxygen from Capillary Blood to Metabolizing Cells
and Within the Cell to the Site of Consumption, the Mitochondria

3. The First Step
Environment Alveolar Space
ATMOSPHERIC OXYGEN TENSION (PiO2 )
 Atmospheric air containing 21 % oxygen at a total
atmospheric pressure of 760 mm Hg at sea level has a pO2
of approximately 160 mm Hg.
ALVEOLAR OXYGEN TENSION
 With every breath, the inspired gas is humidified at 37°C in the upper
airway. The inspired tension of oxygen (PIO2
) is therefore reduced by
the added water vapor. Water vapor pressure is 47 mm Hg at 37°C. In
humidified air, in the trachea the normal partial pressure of O2
at sea
level is 149.7 mm Hg:(760-47)0.21

4. Pulmonary Ventilation
 Respiratory muscle activity of inspiration/expiration cycling
maintains two–way airflow and averaged over several
cycles, maintains a partial pressure of oxygen and carbon
dioxide in the alveolar air of 100 and 40 mm Hg
respectively
 Alveolar pO2 and pCO2 are maintained remarkably constant
by complex neural regulation of the total and alveolar
ventilation.

5.  In order to generate airflow into the lung,
inspiratory muscle contraction overcomes three
forces:
1. The elastic recoil of the lung and chest wall complex
2.The frictional resistance to airflow in the airways and the
frictional resistances between lung and thorax; and
3. Inertial airflow resistance

7. The Second Step
Alveoli Pulmonary Capillary
Factors important in efficient respiratory exchange
between alveolar air and capillary blood in the lung
 1. A large PO2 gradient of approximately 100- 40 mm Hg.
 2. A large surface area available for gas exchange with a
thin diffusion barrier.
 3. A favorable diffusion coefficient for oxygen.
 4. Efficient binding of O2 to Hb in blood.

8.  O2 moves across the alveolar membranes into the
pulmonary capillaries by passive diffusion , across the alveolo
capillary membrane, through the plasma and across the
erythrocyte membrane and binds to Hb.
 This is ‘‘driven’’ by a partial-pressure gradient for oxygen
(pAO2 – pO2)

9.  Alveolar Gas Equation
PAO2 = PiO2 P‒ ACO2/R
where PIO2 is inspired oxygen tension, PACO2 is alveolar CO2 tension (assumed
to equal arterial PCO2), R is the respiratory exchange ratio (normally in the
range of 0.8 to 1.0),
The alveolar oxygen tension is approximately 104mm of Hg
 The factors that determine the precise value of alveolar PO2 are
(1) the PO2 of atmospheric air,
(2) the rate of alveolar ventilation, and
(3) the rate of total body oxygen consumption

10. Arterial Oxygen Tension
PaO2
cannot be calculated like PAO2
but must be measured at room air.
Arterial O2
tension can be approximated by the following formula (in mm
Hg):
PaO2=102-age/3.
The normal PaO2: 97mm Hg

11.  Alveolar–arterial gradient (PAO2 – PaO2)
 The Alveolar–arterial gradient is a measure of the difference between
the alveolar concentration (A) and the arterial (a) concentration of
oxygen. It is used in diagnosing the source of hypoxemia. It helps to
assess the integrity of alveolar capillary unit
 normally about 5–10 mm Hg, but progressively increases with age up to
25 mm Hg
 A high A–a gradient could indicate a patient breathing hard to achieve
normal oxygenation.If lack of oxygenation is proportional to low
respiratory effort, then the A–a gradient is not increased

12. Exchange of Gases in Alveoli – Henry’s Law
 When a liquid is exposed to air containing a particular
gas, molecules of the gas will enter the liquid and
dissolve in it.
 Henry’s law states that “the amount of gas dissolved
in a liquid will be directly proportional to the
partial pressure of the gas in the liquid-gas
interface”.
 As long as the PO2 in the gas phase is higher than
the PO2 in the liquid phase, there will be a net
diffusion of O2 into the blood. Diffusion equilibrium
will be reached only when the PO2 in the liquid
phase is equal to the PO2 in the gas phase.

13. Partial pressures of carbon dioxide and oxygen in inspired air
at sea level and various places in the body

14.  Diffusion of Gases Through the Respiratory Membrane
 Respiratory Unit is composed of a respiratory bronchiole, alveolar
ducts, atria, and alveoli.
 The alveolar walls are extremely thin, and between the alveoli is an almost
solid network of interconnecting capillaries & the alveolar gases are in
very close proximity to the blood of the pulmonary capillaries
 Respiratory Membrane: Gas exchange between the alveolar air and the
pulmonary blood occurs through the membranes of all the terminal
portions of the lungs. All these membranes are collectively known as the
respiratory membrane, also called the pulmonary membrane.

15.  The following are the different layers of the respiratory membrane:
1. A layer of fluid lining the alveolus and containing surfactant that
reduces the surface tension of the alveolar fluid.
2. The alveolar epithelium composed of thin epithelial cells.
3. An epithelial basement membrane.
4. A thin interstitial space between the alveolar epithelium and the
capillary membrane.
5. A capillary basement membrane that in many places fuses with the
alveolar epithelial basement membrane.
6. The capillary endothelial membrane.

17.  Factors That Affect the Rate of Gas Diffusion Through the
Respiratory Membrane
 The thickness of the respiratory membrane :The rate of diffusion through
the membrane is inversely proportional to the thickness of the membrane
and any factor that increases the thickness (eg. Fibrosis, oedema fluid) can
interfere significantly with normal respiratory exchange of gases.
 The surface area of the respiratory membrane: Greater the surface area
greaater is the rate of diffusion. In emphysema, the total surface area of the
respiratory membrane is often decreased because of loss of the alveolar
walls and respiratory exchange of gases is impeded.
 The diffusion coefficient for transfer of each gas through the respiratory
membrane depends on the gas’s solubility in the membrane and, inversely,
on the square root of the gas’s molecular weight.
 The Alveolar–arterial gas gradient.

18. Diffusion from Alveoli to pulmonary
capillary

19. Rate of gas diffusion =
Diffusion coefficient X Pressure gradient x Surface area of the membrane
Thickness of the membrane
 The volume of gas transfer across the alveolar-capillary membrane
per unit time is:
Directly proportional to:
- The difference in the partial pressure of gas between alveoli and
capillary blood.
- The surface area of the membrane.
- The solubility of the gas.
Inversely proportional to:
- Thickness of the membrane.
- Molecular weight of the gas.

20. Diffusing Capacity of the Respiratory Membrane
 the volume of a gas that will diffuse through the membrane each minute for
a partial pressure difference of 1 mm Hg.
 In the average young man, the diffusing capacity for oxygen under resting
conditions averages 21 ml/min/mm Hg.
 The mean oxygen pressure difference across the respiratory membrane
during normal, quiet breathing is about 11 mm Hg. Multiplication of this
pressure by the diffusing capacity (11 × 21) gives a total of about 230
milliliters of oxygen diffusing through the respiratory membrane each
minute
 this is equal to the rate at which the resting body uses oxygen.

21. The Third Step
Pulmonary Systemic Capillaries
Transport of Oxygen in Blood
 Each liter normally contains the number of oxygen molecules equivalent
to 200 ml of pure gaseous oxygen at atmospheric pressure.
 The oxygen is present in two forms:
(1) dissolved in the plasma
(2) reversibly combined with hemoglobin molecules in the RBCs.
 O2 is relatively insoluble in water, only 3 ml can be dissolved in 1 L of
blood at the normal arterial PO2 of 100 mmHg. The other 197 ml of
oxygen in a liter of arterial blood, more than 98 percent of the oxygen
content in the liter, is transported in the erythrocytes reversibly
combined with hemoglobin.

22. Physically dissolved O2
 Only 1.5 % of total O2 in blood.
 Dissolved in plasma and water
of RBC. (because solubility of
O2 is very low)
 It is about 0.3ml of O2 dissolved
in 100ml arterial blood (at PO2
100 mmHg).
 Its amount is directly
proportional to blood PO2.

Chemically combined O2
 98.5 % of total O2 in blood.
 Transported in combination with
Hb.
 It is about 19.5 ml of O2 in 100
ml arterial blood.
 Can satisfy tissue needs.

23. Hemoglobin
.
Each hemoglobin molecule is a protein made
up of four subunits bound together. Each subunit
consists of a molecular group known as heme
and a polypeptide attached to the heme
The four polypeptides of a hemoglobin
molecule are,collectively called globin.
Heme is an iron–porphyrin compound that is an
essential part of the O2
-binding sites; only the
divalent form (+2 charge) of iron can bind O2
.

24.  Each of the four heme groups in a hemoglobin molecule
contains one atom of iron (Fe), to which oxygen binds.
 Thus this chain can exist in one of two forms—
deoxyhemoglobin (Hb) and oxyhemoglobin (HbO2).
 In a blood sample containing many Hb molecules, the fraction of
all the Hb in the form of OxyHb is expressed as the percent Hb
saturation

25. Effect of PO2 on Hemoglobin Saturation: The O2-Hb Dissociation
Curve
 The oxygen–hemoglobin dissociation curve plots the proportion of Hb in
its saturated form on the vertical axis against the prevailing O2 tension on
the horizontal axis.
 Important tool for understanding how blood carries and releases oxygen.
 More specifically it relates between the percentage of O2 carrying capacity
of Hb and PaO2
 It is an S-shaped curve that has 2 parts:
- upper flat (plateau) part.
- lower steep part.

26. Oxygen-hemoglobin dissociation curve

27.  The curve is S-shaped because each Hb molecule contains four subunits;
each binding of O2 to each subunit facilites the binding of the next one.
 This combination of oxygen with hemoglobin is an example of cooperativity,
Explanation
 The globin units of DeoxyHb are tightly held by electrostatic bonds in a
conformation with a relatively low affinity for oxygen.
 The binding of oxygen to a heme molecule breaks some of these bonds
between the globin units, leading to a conformation change such that the
remaining oxygen-binding sites are more exposed.
 Thus, the binding of one O2 molecule to DeoxyHb increases the affinity of the
remaining sites on the same hemoglobin molecule, and so on.

28. The upper flat (plateau)
part of the curve
POPO22
%Hbsaturation%Hbsaturation
1001006060
97 %97 %
90 %90 %
In the pulmonary capillaries (lung, POIn the pulmonary capillaries (lung, PO22 range of 100-60 mmHg).range of 100-60 mmHg).
- At PO2 100 mmHg 97% of Hb is saturated with O2.
- At PO2 60 mmHg 90% of Hb is saturated with O2 (small change in %
Hb saturation).

29.  Physiologic significance:
- Drop of arterial PO2 from 100 to 60 mmHg little decrease
in Hb saturation to 90 % which will be sufficient to meet the body
needs.
This provides a good margin of safety against blood PO2 changes in
pathological conditions and in abnormal situations.
- Increase arterial PO2 (by breathing pure O2
)
little increase in %
Hb saturation (only 2.5%) and in total O2 content of blood.

30. The steep lower part
of the curve
POPO22
%Hbsaturation%Hbsaturation
1001006060
97 %97 %
90 %90 %
In the systemic capillaries (tissue, POIn the systemic capillaries (tissue, PO22 range of 0-60 mm Hg).range of 0-60 mm Hg).
- At PO2 40 mmHg (venous blood) 70% of Hb is saturated with
O2 (large change in % Hb saturation).
At PO2 20 mmHg (exercise) 30% of Hb is saturated with O2.
30 %30 %
70 %70 %
2020 4040

31.  The P50: The PaO2 in the blood at which the hemoglobin is
50% saturated, typically about 26.6 mmHg for a healthy
person.
 Increased P50 indicates a rightward shift of the standard curve, which means
that a larger partial pressure is necessary to maintain a 50% oxygen saturation.
This indicates a decreased affinity
 Conversely, a lower P50 indicates a leftward shift and a higher affinity

32.  SHIFT TO THE LEFT
 As In Pulmonary Capillaries
High pH
Decreased Temp.
Decreased Co2
Fetal Hb
Methaemoglobinemia
 Increased Affinity Of Hb To
Oxygen –Less Release Of
Oxygen
 SHIFT TO THE RIGHT
 As In Placenta And Muscles
Low pH
Increased Temp.
Increased CO2
Increased 2,3 DPG
 Decreased Affinity Of Hb
To Oxygen- More Release
Of Oxygen From Hb
OO
XX
YY
GG
EE
NN
--
HH
BB
CC
UU
RR
VV
EE

34. Clinically important factors altering O2
binding include
1.Hydrogen ion concentration,
2.CO2
tension.
3.Temperature,
4.2,3-diphosphoglycerate (2,3-DPG) concentration.

35. Effect Of pH
 H+
decreases the affinity of Hb molecule for O2 . It does so by combining
with the globin portion of hemoglobin and altering the conformation of
the Hb molecule.
 H+
and O2 both compete for binding to the hemoglobin molecule.
Therefore, with increased acidity, the hemoglobin binds less O2 for a
given PO2 (and more H+
)
 Thus, these effects are a form of allosteric modulation.

36. Effect of CO2:
CO2 affects the curve in two ways:
 Most of the CO2 content (80–90%) is transported as bicarbonate ions. The
formation of a bicarbonate ion will release a proton into the plasma. Hence, the
elevated CO2 content creates a respiratory acidosis and shifts the oxygen–
hemoglobin dissociation curve to the right.
 About 5–10% of the total CO2 content of blood is transported as carbamino
compounds which bind to Hb forming CarbaminoHb. Levels of carbamino
compounds have the effect of shifting the curve to the left.

37. Bohr's Effect
 The Bohr effect is a physiological phenomenon first described in 1904 by the
Danish physiologist Christian Bohr, stating that the “oxygen binding affinity
of Hb is inversely related to the concentration of carbon dioxide & H+
concentration.”
- At tissues: Increased PCO2 & H+
conc. shift of O2-Hb
curve to the right.
-
At lungs: Decreased PCO2 & H+
conc. shift of O2-Hb
curve to the left.
So, Bohr's effect facilitates
i) O2 release from Hb at tissues.
ii) O2 uptake by Hb at lungs.

39. Effect of 2,3DPG to Shift the O2-Hb Dissociation Curve.
 2,3-Bisphosphoglyceric acid (isomer of the glycolytic intermediate
1,3-bisphosphoglyceric acid (1,3-BPG). 2,3-BPG is present in human RBC.

40.  It interacts with deoxygenated Hb beta subunits by decreasing their affinity for
O2, so it allosterically promotes the release of the remaining oxygen molecules
bound to the hemoglobin, thus enhancing the ability of RBCs to release oxygen
near tissues that need it most.
 Increased by: exercise, at high altitude, thyroid hormone, growth
hormone and androgens.
 Decreased by: acidosis and in stored blood.

41. O2 Dissociation Curve Of Fetal Hb
 Fetal Hb (HbF) contains 2α and 2γ polypeptide chains and has no β
chain which is found in adult Hb (HbA).
 So, it cannot combine with 2, 3 DPG that binds only to β chains.
 So, fetal Hb has a dissociation curve to the left of that of adult Hb.
 So, its affinity to O2 is high increased O2 uptake by the fetus
from the mother.

42. Fetal haemoglobin

43. O2 Dissociation Curve Of Myoglobin
 One molecule of myoglobin has one ferrous atom (Hb has 4 ferrous
atoms).
 One molecule of myoglobin can combine with only one molecule of O2 .
 The O2–myoglobin curve is rectangular in shape and to the left of the O2-
Hb dissociation curve.
 So, it gives its O2 to the tissue at very low PO2.
 So, it acts as O2 store used in severe muscular exercise when PO2 becomes

44.  The myoglobin dissociation
curve is a long way to the left
of Hb.
 At each partial pressure of
oxygen, myoglobin holds onto
much more oxygen than Hb.

45. The Fourth Step
Capillary Blood Within the Cell
 The blood entering the capillary with a high PO2 begins to
surrender its oxygen because it is surrounded by an immediate
environment of lower PO2, initially giving off oxygen dissolved
in plasma, and followed by release of oxygen bound to Hb.
 The principal force driving diffusion is the gradient in pO2 from
blood to the cells
 The oxygen dissociation characteristics of Hb facilitate the rapid
and efficient unloading of oxygen within the capillary.
 The O2ultimately diffuses from the microcirculation into the cells
and finally into the mitochondria.

46. Oxygen movement in the lungs and tissues

47. Oxygen content (CaO2)
Total amount of O2 present in 100 ml of Arterial Blood
CaO2=Hb. Bound O2+ dissolved Hb
= [1.34 x Hb x SaO2] + 0.003 x PO2
= [1.34×15×97.5] +0.003×100
=19.9=20ml /dl approx
. =200ml/L
Similarly for Venous blood
CvO2=1.34 × Hb × SvO2 + 0.003 × PvO2
replacing with values we have
CvO2=15 ml/dl
=150 ml/L
Total oxygen content
200 × arterial blood vol. + 150 × venous blood vol.
= 200 × 0.25 × 5+150 × 0.75 × 5
= 250 + 562.5

48. Oxygen delivery (DO2)
Quantity of O2 made available to body in one
minute – O2 delivery or flux
DO2= Q × CaO2 × 10
= Q × 1.34 × Hb × SaO2 × 10
Q - cardiac output
CaO2-arterial oxygen content
Multiplier 10 is used to convert CaO2 from
ml/dl to ml/L
Normal DO2 in adults at rest is 900-1,100 ml/min

49. Oxygen consumption (VO2)
Total amount of O2 consumed by the tissues per unit of time
VO2=Q × (CaO2- CvO2) × 10
rearranging, VO2=Q × 1.34 × Hb × (SaO2-SvO2)
Substituting the values
Normal resting O2 consumption ~ 200 to 300 ml/min
in adult humans

50. The fraction of the oxygen delivered to the capillaries that is taken up into
the tissues is an index of the efficiency of oxygen transport. This is
monitored with a parameter called the oxygen extraction ratio (O2ER),
which is the ratio of O2 uptake to O2 delivery.
O2ER=VO2/DO2
The O2ER is normally about 0.25 (range = 0.2–0.3), . This means
that only 25% of the oxygen delivered to the systemic capillaries is taken up
into the tissues.
Oxygen extraction ratio

51. The DO2–VO2 Relationship
• As O2 delivery (DO2) begins to decrease below normal, the O2 uptake (VO2) initially remains
constant, indicating that the O2 extraction (O2ER) is increasing as the DO2 decreases. Further
decreases in DO2 eventually leads to a point where the VO2 begins to decrease.
• The transition from a constant to a varying VO2 occurs when the O2 extraction increases to a
maximum level of 50% to 60% (O2ER = 0.5 to 0.6). Once the O2ER is maximal, further
decreases in DO2 will result in equivalent decreases in VO2 because the O2ER is fixed and
cannot increase further.
• When this occurs, the VO2 is referred to as being supply-dependent, and the rate of aerobic
metabolism is limited by the supply of oxygen. This condition is known as dysoxia .
• As aerobic metabolism (VO2) begins to decrease, the oxidative production of high energy
phosphates (ATP) begins to decline, resulting in impaired cell function and eventual cell death.

52. The Critical DO2
•The DO2 at which the VO2 becomes supply-dependent is called the critical
oxygen delivery (critical DO2). It is the lowest DO2 that is capable of fully
supporting aerobic metabolism .
• It is identified by the bend in the DO2–VO2 curve .
• Despite the ability to identify the anaerobic threshold, the critical DO2 has
limited clinical value.
• First, the critical DO2 has varied widely in studies of critically ill patient, and it is
not possible to predict the critical DO2 in any individual patient in the ICU.
•Second, the DO2–VO2 curve can be curvilinear (i.e., without a single transition
point from constant to changing VO2) , and in these cases, it is not possible to
identify a critical DO2.

54. DO2 – VO2 relationship in critically
ill
Slope of maximum OER is
less steep
↓
Reduced extraction of
oxygen by tissues
↓
Does not plateau
(consumption remains
supply dependent even
at “supranormal” levels
of DO2)

55. Ultimate Fate of Oxygen
 The oxygen-consuming process in the mitochondrion is localized in the five
sequential enzyme complexes embedded in the inner membrane, comprising the
mitochondrial respiratory chain.
 Four of the five complexes provide reduced NADH transporting free electrons to the
fifth complex, ATP synthase,where oxidative phosphorylation of ADP takes place.
 In the process oxygen is used to generate water and CO2.

56. The Oxygen Cascade

57. The oxygen cascade describes the process of declining oxygen tension from
atmosphere to mitochondria.
 At sea level:159mmHg
 PIO2 : 149mmHg
 PAO2 : 105 mmHg
 PaO2 : 98 mmHg
 PvO2 : 47mmHg
 Intracellular : < 40 mmHg
 Mitochondria: < 5 mmHg
*Any interference to the delivery of oxygen at any point in the cascade, significant
injury can occur downstream. The most graphic example of this is ascension to
altitude.

58. THANK YOU