Human Physiology, 14th edition (2016)

Tissue cells

PlasmaPlasma

CO 2

1

2

3

CO 2 dissolved

in plasma (10%)

Red blood cells

CO 2 combined with

hemoglobin to form

carbaminohemoglobin

(20%)

CO 2 + H 2 OH 2 CO 3

H+ combines

with hemoglobin

HCO 3 –

Cl– (70%)

H 2 CO 3 H+ + HCO 3 –

(Chloride shift)

566 Chapter 16

blood cells because of the catalytic action of the enzyme car-
bonic anhydrase. Since this enzyme is confined to the red
blood cells, most of the carbonic acid is produced there rather
than in the plasma. The formation of carbonic acid from CO 2
and water is favored by the high P^ CO 2 found in the capillaries of
the systemic circulation (this is an example of the law of mass
action; chapter 4, section 4.2).

carbonic anhydrase

C O^2  1 H^2 O H^2 C O^3

high P^ CO 2

The Chloride Shift

As a result of catalysis by carbonic anhydrase within the red
blood cells, large amounts of carbonic acid are produced as
blood passes through the systemic capillaries. The buildup
of carbonic acid concentrations within the red blood cells
favors the dissociation of these molecules into hydrogen
ions (protons, which contribute to the acidity of a solution)
and HC O^3 2 (bicarbonate), as shown by this equation:

H^2 C O^3 → H 1 1 HC O^3 2
The hydrogen ions (H^1 ) released by the dissociation of
carbonic acid are largely buffered by their combination with

Figure 16.38 Carbon dioxide transport and the
chloride shift. Carbon dioxide is transported in three forms:
(1) as dissolved CO 2 gas, (2) attached to hemoglobin as
carbaminohemoglobin, and (3) as carbonic acid and bicarbonate.
Percentages indicate the proportion of CO 2 in each of the forms.
Notice that when bicarbonate ( HC O^3 2 ) diffuses out of the red
blood cells, Cl^2 diffuses in to retain electrical neutrality. This
exchange is the chloride shift.

Figure 16.39 The reverse chloride shift in the

lungs. Carbon dioxide is released from the blood as it travels

through the pulmonary capillaries. A “reverse chloride shift”

occurs during this time, and carbonic acid is transformed into

CO 2 and H 2 O. The CO 2 is eliminated in the exhaled air. Sources

of carbon dioxide in blood include (1) dissolved CO 2 ,

(2) carbaminohemoglobin, and (3) bicarbonate (HC O 32 ).

CO 2 dissolved

in plasma

CO 2 dissolved

in pplaasma

From pulmonary artery To pulmonary vein

Red blood cells

Plasma HCOHCOHHCO 333 – – CCClClCl––

CO 2

Alveoli

1

3

2

Carbaminohemoglobin

CO 2 + H 2 OH 2 CO 3

Hemoglobin + CO 2

HCO 3 – + H+ H 2 CO 3

deoxyhemoglobin within the red blood cells. Although the

unbuffered hydrogen ions are free to diffuse out of the red

blood cells, more bicarbonate diffuses outward into the plasma

than does H^1. As a result of the “trapping” of hydrogen ions

within the red blood cells by their attachment to hemoglobin

and the outward diffusion of bicarbonate, the inside of the red

blood cell gains a net positive charge. This attracts chloride ions

(Cl^2 ), which move into the red blood cells as HC O^3  2 moves out.

This exchange of anions as blood travels through the tissue cap-

illaries is called the chloride shift ( fig. 16.38 ).

The unloading of oxygen is increased by the bonding of

H^1 (released from carbonic acid) to oxyhemoglobin. This is the

Bohr effect, and results in increased conversion of oxyhemoglo-

bin to deoxyhemoglobin. Now, deoxyhemoglobin bonds H^1 more

strongly than does oxyhemoglobin, so the act of unloading its oxy-

gen improves the ability of hemoglobin to buffer the H^1 released

by carbonic acid. Removal of H^1 from solution by its bonding to

hemoglobin then acts through the law of mass action to favor the

continued production of carbonic acid, which increases the ability

of the blood to transport carbon dioxide. In this way, carbon diox-

ide transport enhances oxygen unloading and oxygen unloading

improves carbon dioxide transport.

The Reverse Chloride Shift

When blood reaches the pulmonary capillaries ( fig.  16.39 ),

deoxyhemoglobin is converted to oxyhemoglobin. Because