466
Chapter 13
effect: it alters the hemoglobin molecule so as to shift the
oxygen-hemoglobin dissociation curve to the left, thus decreas-
ing the unloading of oxygen from hemoglobin in the tissues.
As we will see later, the situation is worsened by the fact that
persons suffering from carbon monoxide poisoning do not
show any refl ex increase in their ventilation.
Effects of Blood
P
CO
2
, H
+
Concentration,
Temperature, and DPG Concentration on
Hemoglobin Saturation
At any given
P
O
2
, a variety of other factors infl uence the degree
of hemoglobin saturation. These include blood
P
CO
2
, H
+
con-
centration, temperature, and the concentration of a substance
produced by erythrocytes called
2,3-diphosphoglycerate
(DPG)
(also known as bisphosphoglycerate, BPG). As illus-
trated in
Figure 13–29
, an increase in any of these factors
causes the dissociation curve to shift to the right. This means
that at any given
P
O
2
, hemoglobin has less affi nity for oxygen.
In contrast, a decrease in any of these factors causes the dis-
sociation curve to shift to the left, such that at any given
P
O
2
,
hemoglobin has a greater affi nity for oxygen.
The effects of increased
P
CO
2
, H
+
concentration, and
temperature are continuously exerted on the blood in tissue
capillaries, because each of these factors is higher in tissue-
capillary blood than in arterial blood. The
P
CO
2
is increased
because of the carbon dioxide entering the blood from the tis-
sues. For reasons to be described later, the H
+
concentration is
elevated because of the elevated
P
CO
2
and the release of meta-
bolically produced acids such as lactic acid. The temperature is
increased because of the heat produced by tissue metabolism.
Hemoglobin exposed to this elevated blood
P
CO
2
, H
+
concen-
tration, and temperature as it passes through the tissue capil-
laries has a decreased affi nity for oxygen. Thus, hemoglobin
gives up even more oxygen than it would have if the decreased
tissue-capillary
P
O
2
had been the only operating factor.
The more metabolically active a tissue is, the greater its
P
CO
2
, H
+
concentration, and temperature will be. At any given
P
O
2
, this causes hemoglobin to release more oxygen during
passage through the tissue’s capillaries and provides the more
active cells with additional oxygen. Here, then, is another
local mechanism that increases oxygen delivery to tissues with
increased metabolic activity.
What is the mechanism by which these factors infl uence
the affi nity of hemoglobin for oxygen? Carbon dioxide and
hydrogen ions do so by combining with the globin portion of
hemoglobin and altering the conformation of the hemoglobin
molecule. Thus, these effects are a form of allosteric modu-
lation (Chapter 3). An elevated temperature also decreases
hemoglobin’s affi nity for oxygen by altering its molecular
confi
guration.
Erythrocytes contain large quantities of DPG, which is
present in only trace amounts in other cells. DPG, which is pro-
duced by the erythrocytes during glycolysis, reversibly binds
with hemoglobin, allosterically causing it to have a lower affi n-
ity for oxygen (see Figure 13–29). The net result is that when-
ever DPG levels increase, there is enhanced unloading of oxygen
from hemoglobin as blood fl ows through the tissues. Such
an increase in DPG concentration is triggered by a variety of
100
50
0
Effect of DPG concentration
Hemoglobin saturation (%)
100
50
0
Effect of temperature
Hemoglobin saturation (%)
100
50
0
Effect of acidity
Hemoglobin saturation (%)
No
DPG
Normal
DPG
Added
DPG
20
°
37
°
43
°
Low
acidity
Normal
arterial
acidity
High acidity
40
80
P
O
2
(mmHg)
120
Figure 13–29
Effects of DPG concentration, temperature, and acidity on
the relationship between
P
O
2
and hemoglobin saturation. The
temperature of normal blood, of course, never diverges from 37°C as
much as shown in the fi gure, but the principle is still the same when
the changes are within the physiological range. High acidity and low
acidity can be caused by high
P
CO
2
and low
P
CO
2
, respectively.
Adapted from Comroe.
Figure 13–29
physiological
inquiry
Researchers are developing blood substitutes to meet the demand
for emergency transfusions. What would be the effect of artifi cial
blood in which binding of O
2
is not altered by acidity?
Answer can be found at end of chapter.
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