Hyperkalemia - extra lecture stuff

Fig. 3 Illustration of a normal action potential (solid line) and the action potential as seen in the setting of hyperkalemia (interrupted line). The phases of the action potential are labeled on the normal action potential. Note the decrease in both the resting membrane potential and the rate of phase 0 of the action potential (Vmax) seen in hyperkalemia. Phase 2 and 3 of the action potential have a greater slope in the setting of hyperkalemia compared with the normal action potential.

Phase 0 of the action potential occurs when voltage-gated sodium channels open and sodium enters the myocyte down its electrochemical gradient (Fig. 3). The rate of rise of phase 0 of the action potential (Vmax) is directly proportional to the value of the resting membrane potential at the onset of phase 0.7–9This is because the membrane potential at the onset of depolarization determines the number of sodium channels activated during depolarization, which in turn determines the magnitude of the inward sodium current and the Vmax of the action potential. As illustrated in Figure 4, Vmax is greatest when the resting membrane potential at the onset of the action potential is approximately −75 mV, and does not increase as the membrane potential becomes more negative. Conversely, as the resting membrane potential becomes less negative (that is, −70 mV), as in the setting of hyperkalemia (Fig. 3), the percentage of available sodium channels decreases. This decrease leads to a decrement in the inward sodium current and a concurrent decrease in the Vmax; therefore, as the resting membrane potential becomes less negative in hyperkalemia, Vmax decreases. This decrease in Vmax causes a slow-ing of impulse conduction through the myocardium and a prolongation of membrane depolarization; as a result, the QRS duration is prolonged.

In summary, the early effect of mild hyperkalemia on myocyte function is to increase myocyte excitability by shifting the resting membrane potential to a less negative value and thus closer to threshold potential; but as potassium levels continue to rise, myocyte depression occurs and Vmax continues to decrease.

Hyperkalemia also has profound effects upon phase 2 and phase 3 of the action potential. After the rapid influx of sodium across the cell membrane in phase 0, potassium ions leave the cell along its electrochemical gradient, which is reflected in phase 1 of the action potential. As the membrane potential reaches −40 to −45 mV during phase 0, calcium channels are stimulated, allowing calcium to enter the myocyte. The maximum conductance of these channels occurs approximately 50 msec after the initiation of phase 0 and is reflected in phase 2 of the action potential.7 During phase 2, potassium efflux and calcium in-flux offset one another so that the electrical charge across the cell membrane remains the same, and the so-called plateau phase of the action potential is created (Fig. 3). During phase 3, the calcium channels close, while the potassium channels continue to conduct potassium out of the cell; in this way, the electronegative membrane potential is restored.7 One of the potassium currents (Ikr), located on the myocyte cell membrane, is mostly responsible for the potassium efflux seen during phases 2 and 3 of the cardiac action potential.10 For reasons that are not well understood, these Ikr currents are sensitive to extracellular potassium levels, and as the potassium levels increase in the extracellular space, potassium conductance through these currents is increased so that more potassium leaves the myocyte in any given time period.10 This leads to an increase in the slope of phases 2 and 3 of the action potential in patients with hyperkalemia and therefore, to a shortening of the repolarization time. This is thought to be the mechanism responsible for some of the early electrocardiographic manifestations of hyperkalemia, such as ST-T segment depression, peaked T waves, and Q-T interval shortening.11,12