610
SECTION VII
Respiratory Physiology
hemoglobin in the blood, and the affinity of the hemoglobin
for O
2
.
REACTION OF HEMOGLOBIN & OXYGEN
The dynamics of the reaction of hemoglobin with O
2
make it
a particularly suitable O
2
carrier. Hemoglobin is a protein
made up of four subunits, each of which contains a
heme
moi-
ety attached to a polypeptide chain. In normal adults, most of
the hemoglobin molecules contain two
α
and two
β
chains.
Heme (see Figure 32–7) is a porphyrin ring complex that in-
cludes one atom of ferrous iron. Each of the four iron atoms in
hemoglobin can reversibly bind one O
2
molecule. The iron
stays in the ferrous state, so that the reaction is
oxygenation,
not oxidation. It has been customary to write the reaction of
hemoglobin with O
2
as Hb + O
2
←→
HbO
2
. Because it contains
four deoxyhemoglobin (Hb) units, the hemoglobin molecule
can also be represented as Hb
4
, and it actually reacts with four
molecules of O
2
to form Hb
4
O
8
.
Hb
4
- O
2
←→
Hb
4
O
2
Hb
4
O
2 - O
2
←→
Hb
4
O
4
Hb
4
O
4 - O
2
(^)
←→
Hb
4
O
6
Hb
4
O
6
- O
2
(^)
←→
Hb
4
O
8
The reaction is rapid, requiring less than 0.01 s. The deoxy-
genation (reduction) of Hb
4
O
8
is also very rapid.
The quaternary structure of hemoglobin determines its
affinity for O
2
. In deoxyhemoglobin, the globin units are
tightly bound in a
tense (T) configuration,
which reduces the
affinity of the molecule for O
2
. When O
2
is first bound, the
bonds holding the globin units are released, producing a
relaxed (R) configuration,
which exposes more O
2
binding
sites. The net result is a 500-fold increase in O
2
affinity. In tis-
sue, these reactions are reversed, releasing O
2
. The transition
from one state to another has been calculated to occur about
10
8
times in the life of a red blood cell.
The
oxygen–hemoglobin dissociation curve
relates per-
centage saturation of the O
2
carrying power of hemoglobin to
the P
O 2
(Figure 36–2). This curve has a characteristic sigmoid
shape due to the T–R interconversion. Combination of the first
heme in the Hb molecule with O
2
increases the affinity of the
second heme for O
2
, and oxygenation of the second increases
the affinity of the third, and so on, so that the affinity of Hb for
the fourth O
2
molecule is many times that for the first.
When blood is equilibrated with 100% O
2
(P
O 2
= 760 mm
Hg), the normal hemoglobin becomes 100% saturated. When
fully saturated, each gram of normal hemoglobin contains
1.39 mL of O
2. However, blood normally contains small
amounts of inactive hemoglobin derivatives, and the mea-
sured value in vivo is lower. The traditional figure is 1.34 mL
of O
2
. The hemoglobin concentration in normal blood is
about 15 g/dL (14 g/dL in women and 16 g/dL in men).
Therefore, 1 dL of blood contains 20.1 mL (1.34 mL
×
15) of
O
2
bound to hemoglobin when the hemoglobin is 100% satu-
rated. The amount of dissolved O
2
is a linear function of the
P
O 2
(0.003 mL/dL blood/mm Hg P
O 2
).
In vivo, the hemoglobin in the blood at the ends of the pul-
monary capillaries is about 97.5% saturated with O
2
(P
O 2
= 97
mm Hg). Because of a slight admixture with venous blood
that bypasses the pulmonary capillaries (physiologic shunt),
the hemoglobin in systemic arterial blood is only 97% satu-
rated. The arterial blood therefore contains a total of about
19.8 mL of O
2
per dL: 0.29 mL in solution and 19.5 mL bound
to hemoglobin. In venous blood at rest, the hemoglobin is
75% saturated and the total O
2
content is about 15.2 mL/dL:
0.12 mL in solution and 15.1 mL bound to hemoglobin. Thus,
at rest the tissues remove about 4.6 mL of O
2
from each decil-
iter of blood passing through them (Table 36–1); 0.17 mL of
this total represents O
2
that was in solution in the blood, and
the remainder represents O
2
that was liberated from hemo-
globin. In this way, 250 mL of O
2
per minute is transported
from the blood to the tissues at rest.
FIGURE 36–1
P
O 2
and P
CO 2
values in air, lungs, blood, and
tissues.
Note that both O
2
and CO
2
diffuse “downhill” along gradients
of decreasing partial pressure.
(Redrawn and reproduced with permission
from Kinney JM: Transport of carbon dioxide in blood. Anesthesiology 1960;21:615.)
150120906030(^0) Air Lungs Blood Tissues
(Arterial)
Partial pressure (mm Hg)
(Est)
(Est)
(Venous)
PCO 2
PO 2
FIGURE 36–2
Oxygen–hemoglobin dissociation curve.
pH
7.40, temperature 38 °C. Inset table notes the percentage of saturated
hemoglobin to P
O 2
and dissolved O
2
.
(Redrawn and reproduced with
permission from Comroe JH Jr., et al:
The Lung: Clinical Physiology and Pulmonary
Function Tests,
2nd ed. Year Book, 1962.)
100
Percentage O
saturation of hemoglobin 2
90
80
70
60
50
40
30
20
10
0 102030 405060 70 8090100110
PO 2 (mm Hg)
PO 2
(mm Hg)
% Sat
of Hb
Dissolved
O 2 (mL/dL)
10
20
30
40
50
60
70
80
90
100
13.5
35
57
75
83.5
89
92.7
94.5
96.5
97.5
0.03
0.06
0.09
0.12
0.15
0.18
0.21
0.24
0.27
0.30