534
U N I T 6
Respiratory Function
at which oxygen is released from hemoglobin is deter-
mined largely by tissue uptake. During strenuous exer-
cise, for example, the muscle cells may remove as much
as 15 mL of oxygen per dL of blood from hemoglobin.
Hemoglobin can be regarded as a buffer system that
regulates the delivery of oxygen to the tissues. In order
to function as a buffer system, the affinity of hemoglobin
for oxygen must change with the metabolic needs of the
tissues. This change is represented by a shift to the right
or left in the dissociation curve (Fig. 21-17B). A shift
to the right indicates that the affinity of hemoglobin
for oxygen is decreased and the PO
2
that is available
to the tissues at any given level of hemoglobin satura-
tion is increased. It usually is caused by conditions that
produce an increase in tissue metabolism, such as fever
or acidosis, or by an increase in PCO
2
. High altitude
and conditions such as pulmonary insufficiency, heart
failure, and severe anemia also cause the oxygen dis-
sociation curve to shift to the right. A shift to the left
indicates that the affinity of hemoglobin for oxygen is
increased and the PO
2
that is available to the tissues at
any given level of hemoglobin saturation is decreased.
It occurs in situations associated with a decrease in tis-
sue metabolism, such as alkalosis, decreased body tem-
perature, and decreased PCO
2
levels. The degree of shift
can be determined by the P
50
, or the partial pressure of
oxygen that is needed to achieve a 50% saturation of
hemoglobin. Returning to Figure 22-17B, the dissocia-
tion curve on the left has a P
50
of approximately 20 mm
Hg; the normal curve, a P
50
of 26; and the curve on the
right, a P
50
of 39 mm Hg.
The oxygen content (measured in mL/dL) of blood
represents the total amount of oxygen that is car-
ried in the blood, including the dissolved oxygen and
that carried by the hemoglobin. It is the oxygen con-
tent rather than the PO
2
or hemoglobin saturation that
determines the amount of oxygen that is carried in the
blood and delivered to the tissues. Thus, an anemic per-
son may have a normal PO
2
and hemoglobin satura-
tion level but decreased oxygen content because of the
decreased amount of hemoglobin that is available for
binding of oxygen (Fig. 21-17C).
Carbon DioxideTransport
Carbon dioxide is transported in the blood in three
forms: dissolved in plasma (10%), attached to hemo-
globin (30%), and as bicarbonate (60%). Acid–base
balance is influenced by the amount of dissolved car-
bon dioxide and the bicarbonate level in the blood (see
Chapter 8, Understanding Carbon Dioxide Transport).
As carbon dioxide is formed during metabolism, it
diffuses out of cells into the tissue spaces and then into
the capillaries. The amount of dissolved carbon diox-
ide that can be carried in plasma is determined by the
partial pressure of the gas and its solubility coefficient
(0.3 mL/dL blood/mm Hg PCO
2
). Carbon dioxide is
20 times more soluble in plasma than oxygen. Thus, the
dissolved state plays a greater role in transport of car-
bon dioxide compared with oxygen.
Most of the carbon dioxide diffuses into the red blood
cells, where it either forms carbonic acid or combines
with hemoglobin.
Carbonic acid
(H
2
CO
3
) is formed
when carbon dioxide combines with water (CO
2
+
H
2
O = H
+
+ HCO
3
–
). The process is catalyzed by an
enzyme called
carbonic anhydrase
, which is present in
large quantities in red blood cells. Carbonic anhydrase
increases the rate of the reaction between carbon dioxide
and water approximately 5000-fold. Carbonic acid read-
ily ionizes to form bicarbonate (HCO
3
–
) and hydrogen
(H
+
) ions. The hydrogen ions combine with hemoglobin,
which is a powerful acid–base buffer, and the bicarbon-
ate ion diffuses into plasma in exchange for a chloride
(Cl
–
) ion. This exchange is made possible by a special
bicarbonate-chloride carrier protein in the red blood cell
membrane. As a result of the bicarbonate-chloride shift,
the chloride and water content of the red blood cell is
greater in venous blood than in arterial blood.
In addition to the carbonic anhydrase-mediated reac-
tion with water, carbon dioxide reacts directly with
hemoglobin to form
carbaminohemoglobin.
The com-
bination of carbon dioxide with hemoglobin is a revers-
ible reaction that involves a loose bond, which allows
transport of carbon dioxide from tissues to the lungs,
where it is released into the alveoli for exchange with
the external environment. The release of oxygen from
hemoglobin in the tissues enhances the binding of car-
bon dioxide to hemoglobin; in the lungs, the combining
of oxygen with hemoglobin displaces carbon dioxide.
SUMMARY CONCEPTS
■■
Although the lungs are responsible for the
exchange of gases with the environment, it is
the blood that transports oxygen from the lungs
to the tissues and returns carbon dioxide to the
lungs. Most of the oxygen (97% to 99%) in the
blood is carried in chemical combination with
hemoglobin in red blood cells, with the remaining
1% to 3% being carried in the plasma as a
dissolved gas.
■■
The oxygen dissociation curve is S shaped
with a plateau area, above which an increase in
dissolved oxygen (PO
2
) has minimal or no effect
on hemoglobin saturation.This insures adequate
hemoglobin saturation over a wide range of
dissolved oxygen values.
■■
The oxygen content or amount of oxygen that is
carried in the blood is equal to amount of oxygen
that is carried bound to hemoglobin plus the
dissolved form. Since each gram of hemoglobin
carries approximately 1.34 mL oxygen, it is the
hemoglobin content of the blood rather than
the hemoglobin saturation that determines the
amount of oxygen that the blood can carry.
