8
chapter 1
Water, Acids, Bases, and Buffers
FIGURE 1-6
Schematic representation of the transfer of CO
2
from the alveolus (and its loss in the expired air in the lungs) and
oxygenation of hemoglobin. Note that the sequence of events occurring in the pulmonary capillaries is the opposite of
the process taking place in the tissue capillaries (Figure 1-5). Solid lines indicate major pathways and broken lines
indicate minor pathways. Hb = hemoglobin.
accompanies conversion from Hb
0 2
to HHb+ (Chapters
7 and 28).
As the concentration of HCO
3
(i.e., of metabolic CO
2
)
in red blood cells increases, an imbalance occurs between
the bicarbonate ion concentrations in the red blood cell and
plasma. This osmotic imbalance causes a marked efflux
of HCO, to plasma and consequent influx of Cl" from
plasma in order to maintain the balance of electrostatic
charges. The latter osmotic influx, known as the
chloride
shift,
is accompanied by migration of water to red blood
cells. Thus, transport of metabolic CO
2
in the blood occurs
primarily in the form of plasma bicarbonate formed after
CO
2
diffuses into red blood cells.
FIGURE 1-7
Buffer function of the imidazole/imidazolium functional groups of
histidine residues in protein.
A small percentage of CO
2
entering the red blood
cells combines reversibly with an un-ionized amino group
(-NH
2
) of hemoglobin:
hemoglobin-NH
2
+ C0
2
hemoglobin-NH-COO~+ H+
Hemoglobin-NH-COO- , commonly known as
car-
baminohemoglobin,
is more correctly named hemoglobin
carbamate. Formation of this compound causes a low-
ering of the affinity of hemoglobin for oxygen. Thus,
an elevated concentration of C 0
2
favors dissociation of
oxyhemoglobin to oxygen and deoxyhemoglobin. Con-
versely, C 0
2
binds more tightly to deoxyhemoglobin than
to oxyhemoglobin. All of these processes occurring in
the red blood cells of peripheral capillaries are function-
ally reversed in the lungs (Figure 1-6). Since alveolar Po
2
is higher than that of the incoming deoxygenated blood,
oxygenation of hemoglobin and release of H+ occur. The
H+ release takes place because Hb0
2
is a stronger acid
(i.e., has a lower pK') than deoxyhemoglobin. The released
bicarbonate, which is transported to the red blood cells
with the corresponding efflux of Cl- , combines with the
released H+ to form H
2
C
0 3
. Cellular carbonic anhydrase
catalyzes dehydration of H
2
CC
>3
and release of C 0
2
from
the red blood cells.
Thus, red blood cell carbonic anhydrase which catalyzes
the reversible hydration of C 02, plays a vital role in carbon
dioxide transport and elimination. Carbonic anhydrase is
a monomeric (M.W. 29,000) zinc metalloenzyme and is
