Page 245 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice
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236        ACID-BASE DISORDERS


                                                                 system is increased dramatically. In response to metabolic
                                           ½CO 2diss Š
                           þ
                      log½H Š¼ logK þ log                        acidosis, however, the body goes even further, and PCO 2 is
                                    0
                                    a
                                           ½HCO 3 Š
                                                                 decreased below the normal value of 40 mm Hg, thus
                                                                 increasing the effectiveness of this buffer pair even more.
            Multiplying by  1, we obtain:
                                                                   Consider a closed system in which the bicarbonate–
                                                                 carbonic acid system is the only buffer pair. We will
                                             ½CO 2diss Š
                                                                                                            þ
                      log½H Š¼   logK   log                      assume the following conditions at the start: [H ] ¼
                                     0
                           þ
                                     a
                                            ½HCO 3 Š
                                                                 40 nmol/L, [HCO 3 ] ¼ 24 mmol/L, PCO 2 ¼ 40 mm

                                         ½HCO 3 Š
                          pH ¼ pK þ log                          Hg (dissolved CO 2 ¼ 1.2 mmol/L), and pH ¼ 7.40. If
                                  0
                                  a

                                         ½CO 2diss Š             5 mmol of HCl is added to this closed system, [HCO 3 ]
                                                                 is titrated and decreases to 19 mmol/L, PCO 2 increases to
            Substituting 6.1 for the value of pK a and applying the  206 mm Hg (dissolved CO 2 ¼ 1.2 þ 5 ¼ 6.2 mmol/L),
                                            0
            solubility coefficient for CO 2 , we obtain:         [H ] increases to 260 nmol/L, and pH decreases to
                                                                   þ
                                                                 6.58, a value incompatible with life.

                                       ½HCO 3 Š                    Consider now what would happen if the system were
                       pH ¼ 6:1 þ log
                                      0:03   PCO 2               open and the PCO 2 kept constant at 40 mm Hg by a factor
                                                                 external to the system (i.e., alveolar ventilation). What
            This is the clinically relevant form of the equation and  would happen now if 5 mmol of HCl were added, assum-
            shows that in body fluids, pH is a function of the ratio  ing the same starting conditions? The [HCO 3 ] again

            between HCO 3 concentration and PCO 2 .              decreases to 19 mmol/L, but PCO 2 is fixed at 40 mm

                                                                                                        þ
                                                                 Hg (dissolved CO 2 ¼ 1.2 mmol/L). The [H ] can be
            BODY BUFFERS                                         calculated from the Henderson equation: [H ] ¼ 24
                                                                                                         þ
                                                                 (40)/19 ¼ 50 nmol/L. The pH is 7.30.
            Body buffers can be divided into bicarbonate, which is the  Consider now what would happen if, rather than being
            primarybuffersystemofECF,andnonbicarbonatebuffers    kept constant, the PCO 2 actually decreased to 36.5 mm
            (e.g., proteins and inorganic and organic phosphates),  Hg. This is what would be expected in a patient with met-
            which constitute the primary intracellular buffer system.  abolic acidosis if we use the rule of thumb that PCO 2
            Bone is a prominent source of buffer and can contribute  decreases by 0.7 mm Hg per 1.0 mEq/L decrement in
            calcium carbonate and, to a lesser extent, calcium phos-  plasma HCO 3 concentration. In this setting, [HCO 3 ]


            phate during chronic metabolic acidosis. Bone may even  still decreases to 19 mmol/L, but PCO 2 is 36.5 mm Hg,
            accountfor upto 40% of the buffering ofan acute acid load  and dissolved CO 2 ¼ 0.0301(36.5) ¼ 1.1 mmol/L.
                     9
            in the dog. After administration of NaHCO 3 , carbonate  Again, the [H ] can be calculated from the Henderson
                                                                             þ
            can be deposited in bone.                            relationship: [H ] ¼ 24(36.5)/19 ¼ 46 nmol/L. The
                                                                               þ
                                                                 pH in this setting is 7.34, just slightly below the starting
            BICARBONATE AS A BUFFER IN                           pH of 7.40. This, in essence, is what happens in the body
            EXTRACELLULAR FLUID
                                                                 in response to metabolic acidosis and illustrates the dra-
            If a buffer is most effective within 1 pH unit of its pK a ,  matic effect achieved because the bicarbonate–carbonic
            what accounts for the importance of the bicarbonate sys-  acid system is an open system with PCO 2 closely regulated
            tem (p K a 6.1 vs. ECF p. 7.4)? One factor is the high con-  by alveolar ventilation.
                   0

            centration of HCO 3  (approximately 24 mEq/L vs.
            2 mEq/L for phosphate). However, the most important  PROTEINS AS BUFFERS
            factor is that the bicarbonate–carbonic acid buffer pair  Plasma proteins play a limited role in extracellular buffer-
            functions as an open system. In a closed system, the bicar-  ing, whereas intracellular proteins play an important role
            bonate   and  carbonic  acid  or  dissolved  CO 2    in the total buffer response of the body. The buffer effect
            concentrations must change in a reciprocal manner as  of proteins is the result of their dissociable side groups.
            the following reaction is driven to the left or right:  For most proteins, including hemoglobin, the most
                                                                 important of these dissociable groups is the imidazole
                                            þ
                 CO 2diss þ H 2 O ⇄ H 2 CO 3 ⇄ H þ HCO 3         ring of histidine residues (pK a , 6.4 to 7.0). Amino-termi-
                                                                 nal amino groups (pK a , 7.4 to 7.9) also contribute some-
            In the body, the system is open, and carbonic acid, in the  what to the buffer effect of proteins. Other side groups
            presence of carbonic anhydrase, forms CO 2 , which is  are relatively unimportant because their pK a values are
            eliminatedentirelyfromthesystembyalveolar ventilation.  either too high or too low to be useful in the normal
            Thus,the“acid”memberofthebufferpairisfreetochange    physiologic range of pH. The pK a values for the
            directly with the “salt” member as compensation for met-  dissociable groups of proteins are listed in Table 9-3.
            abolic acidosis occurs. If PCO 2 is kept constant at 40 mm  Hemoglobin is responsible for more than 80% of the
            Hg, the effectiveness of the bicarbonate–carbonic acid  nonbicarbonatebufferingcapacityofwholeblood,whereas
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