section 28.2
Functional Aspects of Hemoglobin
F I G U R E 2 8 - 4
Oxygen dissociation curves for m yoglobin and hem oglobin at several CO 2
pressures. The m yoglobin plot (curve M ) is very sim ilar to the plot for a
hem oglobin subunit (m onom er). Curves A, B, and C are for hem oglobin
at Pco2 = 20, 40, and 80 mm Hg, respectively. Po2 (arterial) and Po2
(venous) indicate norm al values for oxygen tensions. D uring exercise, P o2
(venous) will be lower, around 20-25 m m Hg, because o f the increased
extraction of oxygen from blood by exercising muscle.
of hemoglobin. They decrease the stability of the oxy
form (R-state) of hemoglobin or increase the stability of
the deoxy form (T-state).
Positive allosteric effectors,
allosteric activators,
increase the affinity of hemoglobin
for oxygen. They cause a leftward shift by increasing the
stability of the R-state or by decreasing the stability of
the T-state. Oxygen and carbon monoxide are positive al-
losteric effectors.
A rightward shift decreases the saturation of hemo-
globin with oxygen at any particular
If the blood is
initially fully saturated (arterial blood, Po
= 95 mm Hg),
a rightward shift would increase the amount of oxygen
received by the tissues, as number of moles of oxygen
per unit time. At
= 40 mm Hg, only about 15% of the
oxygen is released from hemoglobin on curve A (85% sat-
uration at 40 mm Hg), while 25% and 50% of the oxygen
is released on curves В and C, respectively. On the other
hand, if the arterial P0, = 45 mm Hg, a rightward shift
would decrease both the initial and final percent satura-
tions to roughly the same extent, and on a molar basis, the
tissues would receive almost the same amount of oxygen
regardless of the position of the curve.
The following examples illustrate this shift (refer to
Figure 28-4). At a normal alveolar Р0, of 95 mm Hg, the
hemoglobin is fully saturated with oxygen. At this Po2,
the degree of saturation is essentially independent of pH,
temperature, and organic phosphate concentration; even
the most right-shifted hemoglobin will be fully saturated
with oxygen. This is the normal condition in arterial blood.
Under abnormal conditions, such as an anatomical shunt
or breathing at a high altitude, the arterial Po
might be
only 45 mm Hg. In this case, the percent saturation in the
lungs would depend heavily on the dissociation curve and
on such factors as temperature, pH, and 2,3-DPG concen-
tration in the erythrocyte. At Po
of 45 mm Hg, under the
conditions for curve B, hemoglobin in the arterial blood
would be about 82% saturated, whereas for curve C it
would be only 62% saturated.
The amount of oxygen released by hemoglobin in the
tissue capillary beds is almost always determined by
the position of the oxygen dissociation curve. At tissue
= 40 mm Hg, hemoglobin will be 75% or 50% sat-
urated with oxygen, depending on whether curve В or
C describes the physiological state. Thus, for curve В at
arterial P
= 95 mm Hg, 100% —
75% = 25% of the
oxygen bound to hemoglobin in the lungs per unit time
would be released to the tissues, whereas for curve C, the
rate of delivery is 100% —
50% = 50%. If the arterial
P0, = 43 mm Hg, the rates of delivery become 82% —
% =
% (curve B) and 62% —
50% = 12% (curve C).
Thus, at low loading pressures, a rightward shift of the oxy-
genation curve makes much less difference in the amount
of oxygen available to the tissues than it does at higher
loading pressures (7% versus 25%), given that the unload-
ing pressures are the same or nearly so. This consideration
is important when evaluating the effect on oxygen delivery
to the tissues of a shift in the oxygen dissociation curve.
However, this explanation is an oversimplification of
actual events
in v iv o .
As blood travels from the lungs to
the tissues and back again, pH, Po2, temperature, and other
factors vary continually. Consequently, the curve that de-
scribes the affinity of hemoglobin for oxygen differs from
one moment to the next.
The need for careful evaluation of all the factors that
affect tissue oxygenation is illustrated by the following
experiment. As part of study of the adaptation of the res-
piratory system to changes in oxygen pressure, it was ob-
served that erythrocytic 2,3-DPG concentration increased
by 25-30% within 24 hours after going from 10 m to
4509 m above sea level, with a corresponding rightward
shift of the oxygen dissociation curve. This finding was in-
terpreted as evidence that 2,3-DPG plays a central role in
the body’s adaptation to anoxic anoxia caused by a change
in altitude. However, the arterial Po
decreased from about
94 mm Hg at 10 m to about 45 mm Hg to 4509 m owing
to a decrease in atmospheric oxygen tension from 149 to
83 mm Hg. Thus, the arterial Po
decreased to a point at
which the supply of oxygen to the tissues was largely inde-
pendent of the position of the curve. Shifting the curve by
the change in 2,3-DPG has no significant effect on oxygen
delivery. Once this fact was recognized, the principal adap-
tive factor was shown to be an increase in respiratory rate.
Increases in hematocrit and mean corpuscular hemoglobin
concentration were also observed.
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