Ganong's Review of Medical Physiology, 23rd Edition

610 SECTION VII Respiratory Physiology
Partial pressure (mm Hg)
150
120
90
60
30
0
PO 2
PCO 2
(Arterial)
(Venous)
Air Lungs Blood Tissues
FIGURE 36–1 PO 2 and PCO 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.)
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 moiety
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 includes
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
(Est)
(Est)
Hb4O6 + O2 ← → Hb4O8 The reaction is rapid, requiring less than 0.01 s. The deoxygenation
(reduction) of Hb4O8 is also very rapid.
The quaternary structure of hemoglobin determines its
affinity for O2 . In deoxyhemoglobin, the globin units are
tightly bound in a tense (T) configuration, which reduces the
affinity of the molecule for O2 . When O2 is first bound, the
bonds holding the globin units are released, producing a
relaxed (R) configuration, which exposes more O2 binding
sites. The net result is a 500-fold increase in O2 affinity. In tissue,
these reactions are reversed, releasing O2 . The transition
from one state to another has been calculated to occur about
108 times in the life of a red blood cell.
The oxygen–hemoglobin dissociation curve relates percentage
saturation of the O2 carrying power of hemoglobin to
Percentage O 2 saturation of hemoglobin
100
90
80
70
60
50
40
30
20
10
PO2 % Sat
(mm Hg) of Hb
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
Dissolved
O 2 (mL/dL)
0.03
0.06
0.09
0.12
0.15
0.18
0.21
0.24
0.27
0.30
0 10 20 30 40 50 60 70
PO2 (mm Hg)
80 90 100110
FIGURE 36–2 Oxygen–hemoglobin dissociation curve. pH
7.40, temperature 38 °C. Inset table notes the percentage of saturated
hemoglobin to PO 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.)
the PO 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 (PO 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 measured
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% saturated.
The amount of dissolved O 2 is a linear function of the
PO 2 (0.003 mL/dL blood/mm Hg PO 2).
In vivo, the hemoglobin in the blood at the ends of the pulmonary
capillaries is about 97.5% saturated with O 2 (PO 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% saturated.
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 deciliter
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 hemoglobin.
In this way, 250 mL of O 2 per minute is transported
from the blood to the tissues at rest.