Ganong's Review of Medical Physiology, 23rd Edition

612 SECTION VIIRespiratory Physiology

CARBON DIOXIDE TRANSPORT

FATE OF CARBON DIOXIDE IN BLOOD

The solubility of CO 2 in blood is about 20 times that of O 2 ;
therefore, considerably more CO 2 than O 2 is present in simple
solution at equal partial pressures. The CO 2 that diffuses into
red blood cells is rapidly hydrated to H 2 CO 3 because of the
presence of carbonic anhydrase. The H 2 CO 3 dissociates to H+
and HCO 3 – , and the H+ is buffered, primarily by hemoglobin,
while the HCO 3 – enters the plasma. Some of the CO 2 in the
red cells reacts with the amino groups of hemoglobin and oth-
er proteins (R), forming carbamino compounds:

Because deoxyhemoglobin binds more H+ than oxyhemo-
globin does and forms carbamino compounds more readily,
binding of O 2 to hemoglobin reduces its affinity for CO 2
(Haldane effect). Consequently, venous blood carries more
CO 2 than arterial blood, CO 2 uptake is facilitated in the tis-
sues, and CO 2 release is facilitated in the lungs. About 11% of
the CO 2 added to the blood in the systemic capillaries is car-
ried to the lungs as carbamino-CO 2.

CHLORIDE SHIFT

Because the rise in the HCO 3 – content of red cells is much

greater than that in plasma as the blood passes through the

capillaries, about 70% of the HCO 3 – formed in the red cells en-

ters the plasma. The excess HCO 3 – leaves the red cells in ex-

change for Cl– (Figure 36–6). This process is mediated by

anion exchanger 1 (AE1; formerly called Band 3), a major

membrane protein in the red blood cell. Because of this chlo-

ride shift, the Cl– content of the red cells in venous blood is

significantly greater than that in arterial blood. The chloride

shift occurs rapidly and is essentially complete within 1 s.

Note that for each CO 2 molecule added to a red cell, there is

an increase of one osmotically active particle in the cell—

either an HCO 3 – or a Cl– in the red cell (Figure 36–6). Conse-

quently, the red cells take up water and increase in size. For

FIGURE 36–4 Formation and catabolism of 2,3-BPG. Note
that 2,3 BPG can be associated with the Embden–Meyerhoff pathway
(see Chapter 1).

H 2 CO

——

P

O

OH

OH

H+ +^ HC

COO−

O

——

P

O

OH

OH

3-Phosphoglyceraldehyde

Glucose 6-PO 4

1,3-Biphosphoglycerate

2,3-Biphosphoglycerate

(2,3-BPG)

3-Phosphoglycerate

Pyruvate

2,3-BPG mutase

2,3-BPG phosphatase

Phospho-

glycerate

kinase

CO 2 +R—N←→R—N

H COOH

H H

CLINICAL BOX 36–1

Hemoglobin & O 2 Binding In Vivo

Cyanosis

Reduced hemoglobin has a dark color, and a dusky bluish

discoloration of the tissues, called cyanosis, appears when

the reduced hemoglobin concentration of the blood in the

capillaries is more than 5 g/dL. Its occurrence depends on

the total amount of hemoglobin in the blood, the degree of

hemoglobin unsaturation, and the state of the capillary cir-

culation. Cyanosis is most easily seen in the nail beds and

mucous membranes and in the earlobes, lips, and fingers,

where the skin is thin.

Effects of 2,3-BPG on Fetal & Stored Blood

The affinity of fetal hemoglobin (hemoglobin F) for O 2 ,

which is greater than that for adult hemoglobin (hemoglo-

bin A), facilitates the movement of O 2 from the mother to

the fetus. The cause of this greater affinity is the poor bind-

ing of 2,3-BPG by the γ polypeptide chains that replace β

chains in fetal hemoglobin. Some abnormal hemoglobins

in adults have low P 50 values, and the resulting high O 2 af-

finity of the hemoglobin causes enough tissue hypoxia to

stimulate increased red cell formation, with resulting poly-

cythemia. It is interesting to speculate that these hemoglo-

bins may not bind 2,3-BPG.

Red cell 2,3-BPG concentration is increased in anemia

and in a variety of diseases in which there is chronic hy-

poxia. This facilitates the delivery of O 2 to the tissues by

raising the PO 2 at which O 2 is released in peripheral capil-

laries. In banked blood that is stored, the 2,3-BPG level falls

and the ability of this blood to release O 2 to the tissues is

reduced. This decrease, which obviously limits the benefit

of the blood if it is transfused into a hypoxic patient, is less

if the blood is stored in citrate–phosphate–dextrose solu-

tion rather than the usual acid–citrate–dextrose solution.