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General Goal. To describe the storage of oxygen and carbon dioxide in blood and tissues, and to provide a
framework for understanding how these stores interact.
Specific Objectives: The student should:
1. be able to name the major regions of PO 2 drop as blood moves from alveolus to mitochondria.
2. know the shape of the myoglobin dissociation curve, and be able to state the two major functions of
myoglobin.
3. know what is meant by the P50 of hemoglobin, be able to sketch a normal oxygen dissociation curve,
and be able to state the significance of the flat portion for oxygen loading, and the steep portion for
oxygen unloading.
4. be able to define oxygen carrying capacity, oxygen content, oxygen saturation, and oxygen partial
pressure.
5. be able to describe the effects of pH, 2,3-DPG, temperature PCO 2 , and PCO on hemoglobin P50.
7. be able to define the Bohr effect, the Haldane effect, and the chloride shift.
8. be able to quantitate the way in which CO2 is carried in plasma and the red cells.
9. be able to describe the significant differences between the oxygen dissociation curve and the carbon
dioxide dissociation curve.
Figure 1. The transport of oxygen in higher organisms requires the presence of concentration gradients at several sites, with the oxygen tension
progressively falling from the lung alveoli to the mitochondria in the peripheral tissues where oxygen is consumed.
A. Although oxygen tension falls in several places, the greatest fall in oxygen tension occurs
across the systemic capillaries.
1. Some tissues extract a greater proportion of oxygen from arterial blood and have a
Pv O2 40 mmHg .
2. Some tissues extract a lesser proportion of the oxygen from arterial blood and
have a Pv O2 40 mmHg .
C. The partial pressure of oxygen in the mitochondria is often considerably lower than the
PO 2 at the end of the systemic capillary. It is therefore unfair to use the Pv O
2
B. Myoglobin is a protein which binds oxygen in red muscle. Red muscle includes the heart
which is a continuously working aerobic organ and red skeletal muscle used in the
performance of aerobic or endurance exercise.
Oxygen/Carbon Dioxide Transport Page 60
Figure 2
2. Myoglobin binding kinetics obey simple mass action laws and are therefore
Michaelis-Menton kinetics.
3. The P50 of myoglobin is the partial pressure at which 50% of the myoglobin
molecules (or 50% of the myoglobin binding sites) have bound O2. This is
by analogy to the Km of an enzyme.
100% x PO2
% Sat =
P50 PO2
Figure 3. The presence of myoglobin can facilitate diffusion within a cell. If the concentration gradient of O2 is in a range over which the
concentration of oxygen greatly affects the degree of its binding to myoglobin, much more of the myoglobin will be oxygenated on the high side of the
gradient. Effective concentration gradients will therefore be established for oxymyoglobin (MbO2) in one direction and for deoxymyoglobin (Mb) in
the opposite direction, so that molecules of the carrier will go to and fro across the concentration gradient, picking up O 2 on the high side, and releasing
it on the low.
1. O2 Partial Pressure. (Also called oxygen tension.) Units are mmHg. The partial
pressure of oxygen is proportional to the amount of O2 dissolved in blood.
Partial pressure differences are of significance in determining the rate of
diffusion between blood and tissue.
2. O2 Content. Units are ml O2/dl blood. These are often written ml/dl. An older
synonym is Vol%. By convention volume units are substituted for molar
units (moles/liter) although the later could be calculated by the gas law.
O2 content is the total amount of oxygen in a deciliter of blood and
includes both dissolved and hemoglobin-bound oxygen, but dissolved [Hb]
is normally negligable. Ignoring dissolved Hb:
%SA O 2 98%
C A O 2 1.36 [Hb] (1.36 ml O2 / g) (15g / dl) 20 ml O 2 / dl
100% 100%
%Sv O 2 75%
C v O 2 1.36 [Hb] (1.36 ml O 2 / g) (15g / dl) 15 ml O2 / dl
100% 100%
% Sat =
Total O 2 Content - dissolved O 2 Content x 100
O 2 Capacity of Hb
Since dissolved O2 content is normally negligible, saturation can be thought of as
content/capacity.
D. Hemoglobin contains 2 alpha chains and 2 beta chains each of which contains 1 heme
group. One molecule of hemoglobin can bind 4 molecules of O2.
1. One g of hemoglobin can bind 1.36 ml O2. (The numbers 1.34 ml O2 and 1.39 ml
O2 are also in common use.)
3. From above, the oxygen binding capacity of blood with a normal hemoglobin is:
100%
(1.36 ml O 2 / g)(15 g / dl) = 20.4 ml O 2 / dl blood
100%
E. When breathing 100% O2 (Pa O2 600 mmHg) dissolved O2 contributes 1.8 ml O2/dl
blood.
Figure 4. O2 dissociation curve (solid line) for pH 7.4 PCO2 40 mmHg and 37°C. The total blood O2 content is also shown for a hemoglobin
concentration of 15 g/100 ml of blood.
F. Sigmoid binding curve. Cooperativity causes the oxygen dissociation curve to display
sigmoid kinetics.
100 x (PO2 ) 2.8
% Sat =
(P50 ) 2.8 ( PO2 ) 2.8
Page 63 Respiratory Physiology
1. The Hill coefficient is 2.8 (not the expected 4) because cooperativity is not
complete.
2. The P50 for hemoglobin (half the binding sites saturated) is 27 mmHg as opposed
to 2.8 mmHg for myoglobin.
3. If there were no cooperativity (Hill coefficient of 1) and a P50 = 27 mmHg, then
hemoglobin would take up less O2 at the lungs (only 79% saturated at
PO 2 100 ) and would give up less O2 as PO 2 fell to venous levels.
Figure 5. Oxygen-hemoglobin dissociation curve. The “driving” pressure for loading O2 onto Hb is arterial O2 tension, which is represented by the
amount of O2 physically dissolved in solution: a = arterial; v = venous; P50 = O2 tension required to saturate 50% of the hemoglobin.
3. Normally hemoglobin gives up less than half its O2. There is reserve in the
system. If systemic capillary PO 2 falls further (eg. in exercise) there is
plenty of additional O2 available from hemoglobin.
%O2 Saturation
Blood PO 2 *Values needed reasonably accurate dissociation
curve. Remember that the PO 2 at which the
10 13
20 36 saturation is 50% (the P50, detailed later) 27 mmHg.
*27 50
30 58
*40 75
50 84
*60 90
80 95
100 97
150 99
200 99.6
Oxygen/Carbon Dioxide Transport Page 64
A. Changes in hemoglobin affinity for oxygen result in a change in P50. Note that the
maximum oxygen capacity is not changed. (change in Km not Vmax.)
Figure 6
1. Increased hemoglobin affinity for O2. The oxygen dissociation curve shifts to
the left. P50 is reduced.
2. Decreased hemoglobin affinity for O2. The oxygen dissociation curve shifts to
the right. P50 is increased.
B. Shifts in oxyhemoglobin dissociation curve have minimal effects on oxygen loading in the
lung because the oxygen dissociation curve is still fairly flat at a PO 2 of 100
mmHg.
C. Shifts in the oxyhemoglobin dissociation curve have a maximal effect on oxygen unloading
at the tissues because the curve is steep at venous PO 2 (eg. 40 mmHg).
D. Hydrogen Ion. Increased [H+] (decreased pH) increases the P50 (decreased O2 affinity)
and shifts the dissociation curve to the right. Decreasing [H+] the opposite effect.
Figure 7
Page 65 Respiratory Physiology
E. Carbon dioxide (Bohr Effect). Increasing PCO 2 increases P50. Decreasing PCO 2
decreases P50.
Figure 8
1. The major portion of the Bohr Effect is due to the fact that increasing PCO 2 causes
a decreased red cell pH (acidosis).
2. A secondary part of the Bohr Effect is due to the fact that CO2 reacts covalently
with hemoglobin to form carbamino hemoglobin which has a reduced O2
affinity.
R NH 2 CO 2 R NH COO H
3. The Bohr Effect plays a significant role in oxygen unloading under normal,
physiological conditions. The P50 of a “venous” oxygen dissociation curve
may be as high as 35 mmHg as compared to the normal arterial value of
27 mmHg.
Oxygen/Carbon Dioxide Transport Page 66
Figure 9
G. Exercise. Increase temperature, increased PCO 2 and decreased pH all promote oxygen
unloading at the tissues by increasing P50 (decreased affinity).
3. Fetal hemoglobin. 2,3-DPG levels do not affect the P50 of fetal hemoglobin.
Page 67 Respiratory Physiology
A. Hemoglobin Concentration. Hemoglobin concentration will change from its normal value
of 15 g/dl as hematocrit changes.
Figure 10
1. Anemia will decrease the oxygen carrying capacity of blood without independently
altering the P50 of blood.
B. Carbon Monoxide. Carbon monoxide binds hemoglobin at the oxygen binding sites to
form carboxyhemoglobin. It has approximately 210 times the affinity of oxygen.
Figure 11.—Dissociation curves for HbO2 and HbCO. Dissociation curves are plotted on the same scale. Maximal saturation of hemoglobin with O 2
is not reached until the PO2 is greater than 120 mmHg; with CO, however, maximal saturation is attained with PCO of less than 1 mmHg.
C. Methemoglobin. The heme groups of hemoglobin normally contain ferrous iron (Fe++)
whether bound to oxygen or not.
R - NH 2 CO 2 R - NH - COO - H +
3. Plasma has little carbonic anhydrase so CO2 forms little carbonic acid in plasma.
Figure 12
Page 69 Respiratory Physiology
1. Dissolved CO2. CO2 can cross the red cell membrane and dissolve in RBC water.
D. Chloride Shift. As HCO 3 is formed it diffuses out of the red cell. Cl- diffuses into the
red cell to maintain electroneutrality. This is the Chloride Shift or Hamburger
Shift.
1. The chloride shift is rapid and is complete before the cells exit the capillary.
2. The osmotic effect of the extra HCO 3 and Cl- in venous red cells causes the
venous RBC volume to increase slightly. For this reason venous
hematocrit slightly exceeds arterial hematocrit.
Figure 13
1. 90% of arterial CO2 stores are carried as HCO 3 with 5% of the stores carried as
dissolved CO2, and 5% of the stores as carbamino compounds.
2. Of the CO2 added in systemic capillaries, 60% is added as HCO 3 , 30% is added
as carbamino compounds and 10% is added as dissolved CO 2.
Oxygen/Carbon Dioxide Transport Page 70
Figure 14
B. Haldane effect. Increasing O2 tension decreases the affinity of hemoglobin for CO2. As a
result the CO2 “dissociation curve” shifts downward.
Figure 15
Page 71 Respiratory Physiology
2. The CO2 dissociation curve is approximately linear (a straight line) in the range of
arterial and venous blood. Thus, if equal volumes of blood of 2 different
CO2 contents are mixed together, the resulting PCO 2 will be half way
between the starting PCO 2 values.
3. The O2 dissociation is curved between arterial and venous points. Thus, if equal
volumes of blood of 2 different O2 contents are mixed together, the
resulting blood will have a PO 2 which is not centered between the original
PO 2 values.
A. The lungs excrete 13,000 mEq a day of CO2 representing an equivalent volume of carbonic
acid. The kidneys excrete 40-80 mEq/day fixed acid.
B. Henderson-Hasselbach Equation
pH 61
. log
HCO 3-
D. The effect of altered PCO 2 on pH depends on whether the bicarbonate buffer system acts
alone or in concert with other buffer systems.
TABLE 1. Effects of adding CO2 to fluids with and without buffers other than bicarbonate
1. CSF. The bicarbonate buffer system works alone and PCO 2 has a larger effect on
pH.
Oxygen/Carbon Dioxide Transport Page 72
12. List four factors which will increase the P 50 for hemoglobin. What is the functional significance of an
increase P50 (rightward shift in the O2 dissociation curve)?
13. How will each of the following affect Pa O2 and oxygen content of arterial blood (C a O2 ) ? a) Anemia;
b) Polycythemia; c) Low PO 2 in inspired air; d) 2,3 DPG; e) Increased Pa CO2 ; f) Fever; g)
Carbon monoxide poisoning; h) Methemoglobinemia
14. What effect does oxygen uptake in the lungs have on the buffering capacity of blood? What does
oxygen unloading in tissues have?
15. How does oxygen unloading in tissues affect carbon dioxide uptake by blood?
16. How does oxygen loading in lungs affect carbon dioxide release from blood?
17. What role does the chloride shift play in carbon dioxide transport by blood?
18. In what form is carbon dioxide carried in blood? What is the percent contribution of each?
19. Calculate the oxygen carrying capacity of a person with hemoglobin concentration of 18 g/dl. What is
his approximate arterial saturation if his C a O2 is 17 ml/dl?
21. Of what significance is the fact that the CO2 dissociation curve is linear over the normal range? Hint:
how does this affect mixing of blood?