10
chapter i
Water, Acids, Bases, and Buffers
acid, bicarbonate ions, and carbonate. Carbonate concen-
tration is negligible; thus,
Total [C02] = [HCO, ] + dissolved[C02] + [H
2
C 03]
But
Dissolved[C02] + [H
2
C 03] = 0.0301 P,
co
2
so that
Finally,
[HCO^] = total[C02] - 0.0301 PCo
2
„
a
1
i 1
/ total [C
0
2] —
0.0301
Pqo2
\
pH = 6.1 + log ( --------------------------------- I
P
6 v
[0.0301 Fco2]
)
(1.17)
Equation (1.17) is useful for calculating the pH from the
total [C
0
2] and
Pco2-
The HCO
3
/H
2
C 0
3
buffer system effectively maintains
a constant blood pH of 7.4 if bicarbonate and H
2
C 0
3
con-
centrations are maintained at a ratio of 20:1. The concen-
tration of HCO
3
is regulated by its selective excretion and
reclamation by the membranes of the renal tubular epithe-
lial cell.
Pqo2
and [H
2
C 03] in the blood can be altered
by changes in the rate and depth of respiration. For ex-
amples,
hypoventilation
(slow, shallow breathing) leads
to increased blood
Pqo2
»
whereas
hyperventilation
(rapid,
deep breathing) has the opposite effect.
Pc
o
2
changes me-
diated by the lungs are more rapid than [HCOJ] changes
affected through the kidneys (Chapter 39).
Nonbicarbonate Buffers in Blood
Other important nonbicarbonate blood buffers are protein
and phosphate. The predominant buffer system in the red
blood cells is hemoglobin. Protein amino acid side chains
(R-groups) that act as buffers are carboxylate groups of
glutamate and aspartate and the weakly basic groups of
lysine, arginine, and histidine. To be effective, the pK'
value of a buffer should be close to the pH of the system to
be buffered. Except for the R-group of histidine, which is
an imidazolium group (Figure 1 -7), the pK' values of the
other amino acids mentioned above are not close enough to
the physiological pH of blood to be effective buffers. The
imidazolium group has a pK' value of 6.5 but it can vary
from 5.3 to 8.3 depending on differences in electrostatic
environment either within the same protein molecule or
in different proteins. Another potential buffering group in
protein is the cc-amino group of the amino acid residues at
the amino terminus of the protein. This group has a pK
7
value ranging from 7.8 to 10.6, with a typical value of
about
8
(acid-base properties of amino acids and proteins
are discussed in detail in Chapters 2 and 3). In plasma,
FIGURE 1-8
Titration profile of phosphoric acid (H
3
PO
4
) with sodium hydroxide
(NaOH). The three pK' values correspond to three buffer regions. The
physiological buffering occurs at the pK' region with H
2
PO
4
(acid) and
HPO
4
' (conjugate base) ionic species.
the protein buffer system has a limited role; the principal
plasma buffer is the bicarbonate-carbonic acid system.
Compared with hemoglobin in the red blood cells and
HCO
3
/H
2
C 0
3
in plasma, phosphates (both organic and in-
organic) play minor roles in physiological buffering. Phos-
phoric acid (H
3
P04) has three dissociable protons:
H3P04 <=! H2PC>4 + H+
pK'i = 1.9
(1.18)
H2PC>4 ^ HPO^- + H+
pK2 = 6.8
(1.19)
HPC>4_ <=>
PC>4_ + H+
pK3 = 12.4
(1.20)
The titration profile of phosphoric acid with NaOH is
shown in Figure 1-8. The principal dissociation expres-
sion functioning at a given pH depends on which pK'
is closest to the pH. At a plasma pH of 7.4, the impor-
tant conjugate pair is HPO^ÆEPOj). The Henderson-
Hasselbalch equation can be used to obtain the value of
the ratio HPO
4
WH
2
PO
4
at pH 7.4:
log
7.4 =
6 . 8
+ log
{
^
=
0 . 6
[h jpo , ]
and
[HPQj-]
[H
2
PO
4
-]
[HPO^-J
[H2P04-]
(
1
.
21
)
= 4
As was the case for the bicarbonate-carbonic acid sys-
tem, the conjugate base form (HPO
4
“ ) of the phosphate
buffer is present in large (fourfold) excess compared to
the acid form (H
2
PC
>4
) and provides acid buffering capac-
ity. Since the body metabolism produces more acid than
