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Introduction to Acid-Base Disorders 237
TABLE 9-3 pK a Values for R R
0
Dissociable Groups CH 2 CH 2
Found in Proteins
HC C HC C
+ H +
Dissociable Group (Amino Acid) pK a
0
+
HN NH N NH
a-Carboxyl 3.6-3.8 CH CH
b-Carboxyl (aspartic acid) 4.0 Figure 9-3 The imidazole group of histidine. (From Madias NE,
g-Carboxyl (glutamic acid) 4.0 Cohen JJ. Acid-base chemistry and buffering. In: Cohen JJ, Kassirer
Imidazole (histidine) 6.4-7.0 JP, editors. Acid-base. Boston: Little, Brown, 1982: 16.)
a-Amino 7.4-7.9
Sulfhydryl (cysteine) 9.0
e-Amino (lysine) 9.8-10.6
(approximately 40 mEq/L in skeletal muscle cells), and
Phenolic (tyrosine) 8.5-10.9
less important in ECF, where its concentration is much
Guanidino (arginine) 11.9-13.3
lower (approximately 2 mEq/L). Inorganic phosphate
From Madias NE, Cohen JJ: Acid-base chemistry and buffering. In Cohen is an important buffer in urine because the range of pH
JJ, Kassirer JF, editors: Acid-base, Boston, 1982, Little, Brown & Co., in tubular fluid (6.0 to 7.0) includes the pK a of the
p. 16. Na 2 HPO 4 /NaH 2 PO 4 system (6.8). This buffer pair
functions in the excretion of titratable acidity in urine
plasma proteins contribute 20%. Of the plasma proteins, (see the Titratable Acidity section later).
albumin is much more important than are the globulins. PHYSIOLOGIC LINES OF
The buffer value of albumin is 0.12 to 0.14 mmol/g/pH
unit, whereas that of globulins is 0 to 0.08 mmol/g/pH DEFENSE IN ACID-BASE
unit. 38,69,71 The difference results from a larger number DISTURBANCES
of histidine (Fig. 9-3) residues in albumin.
The isoelectric point (pI) is the pH at which a sub- An overview of the body buffer response is provided by
stance has no tendency to move in an electric field and contrasting the body’s response to a nonvolatile, or fixed,
thus has no net charge. For proteins, this means that acid (e.g., HCl) and its response to the volatile acid CO 2 .
the sum of the charges on the negative side groups The hydrogen ions from a fixed acid load immediately
(e.g., R–COO ) equals the sum of the charges on the titrate bicarbonate ions in ECF and then titrate intracellu-
þ
positive side groups (e.g., R–NH 3 ). At physiologic pH lar buffers(e.g.,proteins,phosphates).This physicochem-
(7.4), plasma proteins are polyanions because their pIs ical response occurs within minutes and protects ECF pH.
range from 5.1 to 5.7. The net negative charge on plasma Alveolar ventilation is stimulated, and PCO 2 is decreased to
proteins in mEq/L can be calculated as: 38 below normal. This response, which begins immediately
and is complete within hours, minimizes the change in
½ Pr b ðpH pIÞ pH because the ratio of HCO 3 to PCO 2 is normalized.
Finally, the kidneys regenerate titrated HCO 3 ,pH
where [Pr] is the concentration of plasma proteins in increases, alveolar ventilation decreases, and PCO 2 returns
grams per liter, b is the buffer value of plasma proteins to normal. The renal response begins within hours but
in millimoles per gram per pH unit, pH is the ECF pH, requires 2 to 5 days to reach maximal effectiveness.
and pI is the isoelectric point of plasma proteins. Using The volatile acid CO 2 cannot be buffered by HCO 3 ,
this formula, it can be calculated that, at a normal plasma and the hydrogen ions resulting from the dissociation of
protein concentration of 7 g/dL, average buffer value of carbonic acid must titrate intracellular buffers, such as
0.1 mmol/g/pH unit, and pI range of 5.1 to 5.7, plasma proteins (especially hemoglobin in red cells) and
proteins contribute 12 to 16 mEq/L of negative charge. phosphates. Renal adaptation is characterized by
In dogs, the mean contribution of charge by plasma increased HCO 3 reabsorption and net acid excretion,
proteins is approximately 16 mEq/L. 16,76 mechanisms that require 2 to 5 days to achieve maximal
effectiveness. The buffer response of the body to the pri-
PHOSPHATES AS BUFFERS mary acid-base disorders is considered in more depth in
The most important intracellular buffers are proteins and the chapters on those disorders (see Chapters 10 and 11).
inorganic and organic (e.g., adenosine triphosphate
[ATP], adenosine diphosphate [ADP], 2,3-diphospho- TERMINOLOGY
glycerate) phosphates. The pK a value for H 2 PO 4 is
6.8, and pK a values for organic phosphates range from The terms acidosis and alkalosis refer to the pathophysi-
6.0 to 7.5. Inorganic phosphate is a more important ologic processes that cause net accumulation of acid or
buffer intracellularly, where its concentration is high alkali in the body. The terms acidemia and alkalemia