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Disorders of Potassium: Hypokalemia and Hyperkalemia  93


            the intracellular concentration of potassium is much  skeletal muscle of control animals was  90.1 mV. 20
            higher than its extracellular concentration. As a result,  The resting cell membrane potential plays a vital role in
             þ
            K ions diffuse out of the cell down their concentration  the normal function of skeletal and cardiac muscle,
            gradient. However, the cell membrane is impermeable  nerves, and transporting epithelia.
            to most intracellular anions (e.g., proteins and organic
            phosphates). Therefore, a net negative charge develops  THE THRESHOLD CELL
                            þ
            within the cell as K ions diffuse out, and a net positive  MEMBRANE POTENTIAL
            charge accumulates outside the cell. Consequently, a
            potential difference is generated across the cell membrane.  The threshold cell membrane potential is reached when
              The principal extracellular cation is sodium, and it  sodium permeability increases to the point that sodium
            enters the cell relatively slowly down its concentration  entry exceeds potassium exit, depolarization becomes
            and electrical gradients, because the permeability of the  self-perpetuating, and an action potential develops. The
            cell membrane to potassium is 100-fold greater than its  ability of specialized cells to develop an action potential
                                              þ
            permeability to sodium. Diffusion of K ions from the  is crucial to normal cardiac conduction, muscle contrac-
            cell continues until the ECF acquires sufficient positive  tion, and nerve impulse transmission. The excitability of a
            charge to prevent further diffusion of K þ  ions out of  tissue is determined by the difference between the resting
            the cell. The ratio of the intracellular to extracellular  and threshold potentials (the smaller the difference, the
                                       þ
                                             þ
            concentrations of potassium ([K ] I /[K ] O ) is the major  greater the excitability).
            determinant of the resting cell membrane potential as  Hypokalemia increases the resting potential (i.e.,
            described by the Nernst equation:                   makes it more negative) and hyperpolarizes the cell,
                                                                whereas hyperkalemia decreases the resting potential
                                           þ
                                        ½K Š I                  (i.e., makes it less negative) and initially makes the cell
                          E m ¼ 61 log
                                      10  þ
                                        ½K Š                    hyperexcitable (Fig. 5-2). If the resting potential
                                            O
                                                                decreases to less than the threshold potential, depolariza-
            The Goldman-Hodgkin-Katz equation is a modification  tion results, repolarization cannot occur, and the cell is no
            of the Nernst equation that allows prediction of E m based  longer excitable. Translocation of potassium between
            on the ionic permeability characteristics of the cell mem-  body compartments results in a greater change in the
            brane to sodium and potassium and the concentrations  ratio  of  intracellular  to  extracellular  potassium
                                                                                       þ
                                                                                 þ
            of these ions inside and outside the cell:          concentrations ([K ] I /[K ] O ) than does a change in
                                                                total body potassium. In the former instance, the potas-
                                       þ         þ
                                  rPk½K Š þ P Na ½Na Š I        sium concentrations of the two compartments change in
                                        I
                   E m ¼ 61 log
                               10     þ          þ
                                 rPk½K Š þ P Na ½Na Š           opposite directions, whereas in the latter instance, they
                                        O          O
                                                                change in the same direction.
            where P Na and P K are the membrane permeabilities for  Membrane excitability also is affected by ionized
            sodium and potassium. The term r is included in the  calcium concentration and acid-base balance. Calcium
            equation to account for the effect of the electrogenic  affects the threshold potential rather than the resting
                  þ
              þ
            Na ,K -ATPase pump under steady-state conditions.
            This term is assigned the Na/K transport ratio of 3:2
                                                                   +30
            so that r ¼ 1.5. If the membrane permeability for potas-
                                                                                Action
            sium is assigned a value of 1.0 and the cell membrane is            potential
                                                                     0
            100 times more permeable to potassium than sodium:
                                                  þ                –30
                                 1:5½K þ Š þ 0:01½Na Š
                   E m ¼ 61 log 10      I           I
                                                  þ
                                 1:5½K þ Š þ 0:01½Na Š O          Millivolts  –60  Normal
                                       O
                                                                       threshold
            For example, using the hypothetical ECF and ICF
                                                                       Resting
            concentrations of sodium and potassium given at the    –90
            beginning of this chapter:
                                                                   –120
                                  1:5½140Šþ 0:01½10Š                                       +    +       ++    ++
                    E m ¼ 61 log                                           Normal      Low K  High K  High Ca  Low Ca
                                10
                                   1:5½4Šþ 0:01½140Š            Figure 5-2 Effects of serum calcium and potassium on membrane
                                                                potentials of excitable tissues. The concentration of potassium in
                     E m ¼ 61 log ð28:4Þ¼  89mV                 extracellular fluids affects the resting potential, whereas calcium
                                 10
                                                                concentrations alter the threshold potential. (From Leaf A, Cotran
            In one study of dogs with potassium deficiency, the  R. Renal pathophysiology. New York: Oxford University Press,
            predicted E m was  86.6 mV and the measured E m in  1976: 116.)
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