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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 PrŠ  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
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