SECTION
1.2
Buffers
7
FIGURE 1-5
Schematic representation of the transport of CO
2
from the tissues to the blood. Note that the majority of CO
2
is
transported as HCOJ in the plasma and that the principal buffer in the red blood cell is hemoglobin. Solid lines refer to
major pathways, and broken lines refer to minor pathways. Hb = hemoglobin.
Other acids that are products of metabolism are lactic
acid, acetoacetic acid,
f
-hydroxybutyric acid, phospho-
ric acid, sulfuric acid, and hydrochloric acid. The organic
acids (e.g., lactate, acetoacetate, and /i-hydroxybutyrate)
are normally oxidized further to CO
2
and H
2
0. The
hydrogen ions and anions contributed by mineral acids
and any unmetabolized organic acids are eliminated via
the excretory system of the kidneys. Thus, although body
metabolism produces a large amount of acid, a constant pH
is maintained by transport of H+ ions and other acid an-
ions in buffer systems and by elimination of C 0
2
through
alveolar ventilation in the lungs and through excretion of
aqueous acids in the urine.
Metabolic activities continuously release C 0
2
to the
blood (Figure 1-5), and the lungs continuously elimi-
nate C 0
2
(Figure 1-6). As oxygen is consumed in pe-
ripheral tissues, C
0 2
is formed and its pressure
(Pco2)
builds to about 50 mm Hg, whereas the blood entering
the tissue capillaries has a PCo
2
°f about 40 mm Hg.
Because of this difference in
Pco2
values, C 0
2
diffuses
through the cell membranes of the capillary endothelium
and the blood
Pco2
rises to 45-46 mm Hg. Despite this
increase in PCo2, the blood pH value drops by only about
0.03 during the flow from the arterial capillary (pH 7.41)
to the venous capillary (pH 7.38) as a consequence of
buffering.
About 95% of the C 0
2
entering the blood diffuses into
the red blood cells. Within the red blood cells, the enzyme
carbonic anhydrase catalyzes conversion of most of the
C 0
2
to H
2
C 03:
c o
2
+ H
2 0
H
2
C
0
3
H
2
C 0
3
dissociates to H+ and HCOjT. Although H
2
C 0
3
is a weak acid, its dissociation is essentially
1 0 0
% be-
cause of removal of H+ ions by the buffering action of
hemoglobin. The presence of C 0
2
and the production of
H+ cause a reduction in the affinity of hemoglobin for
oxygen. Oxyhemoglobin (Hb02) consequently dissoci-
ates into oxygen and deoxyhemoglobin (Hb). This effect
of pH on the binding of 0
2
to hemoglobin is known as the
Bohr effect
(Chapter 28).
Oxygen diffuses into the tissues because the Po
2
in
blood is greater than the Po
2
in tissue cells and be-
cause protonated deoxyhemoglobin (HHb) is a weaker
acid than Hb0
2
and thereby binds H+ more strongly
than Hb02. When purified Hb0
2
dissociates at pH 7.4
to yield oxygen and Hb, the Hb binds 0.7 mol of H+ per
mole of oxygen released. However, under physiological
conditions in whole blood, the Hb combines 0.31 mol
of H+ per mole of oxygen released. This process is re-
versible. The remainder of the H+ is buffered by phos-
phate and proteins other than hemoglobin. The major
buffering group involved in the transport of H+ is an im-
idazolium group of a histidine residue in hemoglobin.
The imidazolium group has a pK' value of about 6.5
(Figure 1-7 depicts the reactions). The difference in acid-
base properties between the two forms of hemoglobin
molecules is explained by the conformational change that
