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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 I (i.e., makes it less negative) and initially makes the cell
E m ¼ 61 log
10 þ
½K 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 þ P Na ½Na I sium concentrations of the two compartments change in
I
E m ¼ 61 log
10 þ þ
rPk½K þ P Na ½Na 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 þ 0:01½Na
E m ¼ 61 log 10 I I
þ
1:5½K þ þ 0:01½Na 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
1:5½140þ 0:01½10 + + ++ ++
E m ¼ 61 log Normal Low K High K High Ca Low Ca
10
1:5½4þ 0:01½140 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.)