CHAPTER 36
Gas Transport & pH in the Lung 611FACTORS AFFECTING THE AFFINITY
OF HEMOGLOBIN FOR OXYGEN
Three important conditions affect the oxygen–hemoglobin dis-
sociation curve: the
pH,
the
temperature,
and the concentra-
tion of
2,3-biphosphoglycerate (BPG; 2,3-BPG).
A rise in
temperature or a fall in pH shifts the curve to the right (Figure
36–3). When the curve is shifted in this direction, a higher P
O 2
is required for hemoglobin to bind a given amount of O
2
. Con-
versely, a fall in temperature or a rise in pH shifts the curve to
the left, and a lower P
O 2
is required to bind a given amount of
O
2
. A convenient index for comparison of such shifts is the P
50
,
the P
O 2
at which hemoglobin is half saturated with O
2
. The
higher the P
50
, the lower the affinity of hemoglobin for O
2
.
The decrease in O
2
affinity of hemoglobin when the pH of
blood falls is called the
Bohr effect
and is closely related to the
fact that deoxygenated hemoglobin (deoxyhemoglobin) binds
H
- more actively than does oxygenated hemoglobin (oxy-
hemoglobin). The pH of blood falls as its CO
2
content
increases, so that when the P
CO 2
rises, the curve shifts to the
right and the P
50
rises. Most of the unsaturation of hemoglobin
that occurs in the tissues is secondary to the decline in the P
O 2
,
but an extra 1–2% unsaturation is due to the rise in P
CO 2
and
consequent shift of the dissociation curve to the right.
2,3-BPG is very plentiful in red cells. It is formed from 3-
phosphoglyceraldehyde, which is a product of glycolysis via
the Embden–Meyerhof pathway (Figure 36–4). It is a highly
charged anion that binds to the
β
chains of deoxyhemoglobin.
One mole of deoxyhemoglobin binds 1 mol of 2,3-BPG. In
effect,
HbO
2
+ 2,3-BPG
←→
Hb – 2,3-BPG + O
2
In this equilibrium, an increase in the concentration of 2,3-
BPG shifts the reaction to the right, causing more O
2
to be
liberated.
Because acidosis inhibits red cell glycolysis, the 2,3-BPG
concentration falls when the pH is low. Conversely, thyroid
hormones, growth hormones, and androgens can all increase
the concentration of 2,3-BPG and the P
50
.
Exercise has been reported to produce an increase in 2,3-
BPG within 60 min, although the rise may not occur in
trained athletes. The P
50
is also increased during exercise,
because the temperature rises in active tissues and CO
2
and
metabolites accumulate, lowering the pH. In addition, much
more O
2
is removed from each unit of blood flowing through
active tissues because the tissues’ P
O 2
declines. Finally, at low
P
O 2
values, the oxygen–hemoglobin dissociation curve is
steep, and large amounts of O
2
are liberated per unit drop in
P
O 2. Some clinical features of hemoglobin are discussed in
Clinical Box 36–1.
MYOGLOBIN
Myoglobin is an iron-containing pigment found in skeletal mus-
cle. It resembles hemoglobin but binds 1 rather than 4 mol of O
2
per mole. Its dissociation curve is a rectangular hyperbola rather
than a sigmoid curve. Because its curve is to the left of the hemo-
globin curve (Figure 36–5), it takes up O
2
from hemoglobin in
the blood. It releases O
2
only at low P
O 2
values, but the P
O 2 in ex-
ercising muscle is close to zero. The myoglobin content is great-
est in muscles specialized for sustained contraction. The muscle
blood supply is compressed during such contractions, and myo-
globin may provide O 2 when blood flow is cut off.TABLE 36–1 Gas content of blood.
mL/dL of Blood Containing 15 g of HemoglobinArterial Blood (PO 2 95 mm
Hg; PCO 2 40 mm Hg; Hb
97% Saturated)Venous Blood (PO 2 40
mm Hg; PCO 2 46 mm Hg;
Hb 75% Saturated)Gas Dissolved Combined Dissolved Combined
O 2 0.29 19.5 0.12 15.1
CO 2 2.62 46.4 2.98 49.7
N 2 0.98 0 0.98 0FIGURE 36–3 Effects of temperature and pH on the oxygen–hemoglobin dissociation curve. Both changes in temperature (left) and
pH (right) can alter the affinity of hemoglobin for O 2. Plasma pH can be estimated using the modified Henderson–Hasselbalch equation, as shown.
(Redrawn and reproduced with permission from Comroe JH Jr., et al: The Lung: Clinical Physiology and Pulmonary Function Tests, 2nd ed. Year Book, 1962.)
1008060402002040 60 801008060402002040 60 8010 °
20 °38 °43 °Effect of temperature7.6
7.4 7.2Effect of pHpH arterial blood ≅ 7.40
pH venous blood ≅ 7.36pH = 6.10 + log[HCO 3 −]
0.0301 PCO 2