eLearning - Cardiac Electrophysiology in Hyperkalemia Flashcards
Patient is given thiopental and succinyl choline, and developes hyerkalemia. Where did the potassium come from that produced the increased plasma potassium concentration in this patient?
Succinylcholine binds to and activates acetylcholine (ACh) receptors at muscle neuromuscular junctions. Accordingly, it depolarizes the subsynaptic membrane. Since succinylcholine resists hydrolysis by acetylcholine esterase, the depolarization of the subsynaptic membrane is prolonged leading to inactivation of sodium channels in the vicinity of the subsynaptic membrane. By this mechanism, the muscle becomes unexcitable inducing a relaxed muscle state. However, increased K-loss from the muscle will occur since potassium efflux through open K-channels increases as membrane potential moves more positive; difference between membrane potential and potassium Nernst potential increases. Succinylcholine produces some Kloss from normal individuals but the effect is blunted by the fact that this loss is confined to K-channels near the endplate. The hypersensitivity of some individuals to succinylcholine is due to the existence of ACh receptors in extrajunctional areas. The extrajunctional receptors increase the area of depolarized membrane and K-efflux though open K-channels. In some rare cases, succinylcholine induces rhabdomyolysis (i.e., breakdown of the muscle membrane).
With regards to SA-node cells, what effect does hyperkalemia have on 1) maximum diastolic potential, 2) rate of phase 4 depolarization, 3) rate of phase 0 depolarization, and 4) rate of phase 3 repolarization? Which of these would contribute to the production of a bradycardia?
Maximum diastolic potential becomes more negative, rate of phase 4 depolarization is decreased, rate of phase 0 depolarization is decreased, and rate of phase 3 repolarization is increased. Bradycardia is related to the more negative maximum diastolic potential and decreased rate of phase 4 depolarization.
In regards to question 2, by what mechanism(s) does hyperkalemia produce each of the effects on SA-node cells?
All of these effects are produced by the increase in potassium conductance that occurs in hyperkalemia.
What effects does hyperkalemia to have on 1) PR interval, 2) RT interval, and 3) T-wave?
PR interval is increased, RT interval is decreased, and T-wave is increased in magnitude.
With regards to question 4, by what mechanism does hyperkalemia produce each of the effects on the ECG?
The increase in PR interval results from slowed conduction velocity of both atrial and AV-node action potentials. Enhanced K-conductance contributes to both events. In the atrium, increased sodium channel inactivation due to membrane depolarization also acts to slow conduction. The decrease in RT-interval reflects the decrease in ventricular action potential duration caused by increased K-current due to increased Kconductance. The increased magnitude of the T-wave reflects faster phase 3 repolarization caused by increased K-current due to increased K-conductance.
Calcium, insulin, bicarbonate and epinephrine were administered to this patient in an attempt to abort the deleterious cardiac effects of the hyperkalemia? By what mechanism(s) does each of these produce a beneficial effect?
Increased extracellular calcium, in the presence of hyperkalemia, returns excitability related to Na-dependent action potentials towards normal. Extracellular calcium affects the voltage-dependency of sodium channel inactivation (i.e., the position of the inactivation curve on the voltage axis). By increasing extracellular calcium, some sodium channels that were inactivated by the hyperkalemia-induced depolarized state 4 of the membrane are converted to the resting state. The recovery of resting sodium channels acts to return excitability toward normal. Increased calcium produces this effect by shifting the sodium channel inactivation curve toward more depolarized potentials.
Bicarbonate acts to return excitability towards normal by shifting potassium into the cell from the ECF thereby shifting resting potential more negative. By reducing extracellular hydrogen ion concentration, bicarbonate enhances sodium transport into the cell via the Na-H exchanger. The increased Na-influx acts to increase intracellular sodium ion concentration. In turn this enhances Na-K pump thereby moving potassium into the cell.
By stimulating the Na-K pump, insulin also acts to move potassium into the cell.
Epinephrine acts to restore heart rate and AV-node conduction towards normal. It does this by increasing the funny sodium current responsible for phase 4 depolarization in SA-node cells. It also increases L-type calcium current thereby increasing the rate of phase 0 depolarization in AV-node cells (also in SA-node cells). This increases action potential conduction velocity of these cells
Within about a 10 min period, this patient’s plasma potassium concentration decreased from 9.8 to 4.1 mEq/L. This represents a loss of how many moles of potassium from the plasma? Where did this potassium go?
Since interstitial and plasma potassium concentration are in equilibrium, the concentration of potassium in the ECF must be reduced by 5.7 mEq/L in order to reduce plasma potassium concentration from 9.8 mEq/L to 4.1 mEq/L.
ECF volume is about 20% (i.e., body weight x 0.6 x 0.33) of total body weight. For the patient in this case this would be about 23 liters. A loss of about 131 mEq (23 x 5.7) from the ECF would be required to reduce ECF potassium concentration by 5.7 mEq/L. Since the kidneys cannot excrete this much potassium in 10 minutes (daily excretion of potassium by the kidneys is about 95 mEq), it seems reasonable to conclude that the potassium went into cells.
With regards to question 7, does the potassium loss from the plasma account for all of the potassium loss from the extracellular compartment? Explain you answer.
Since the interstitial compartment, rather the plasma compartment, is contiguous to cell membranes, the movement of potassium into cells requires the movement of potassium out of the interstitial compartment and into the cell. The reduction of plasma potassium from 9.8 to 4.1 mEq/L requires that interstitial potassium concentration be reduced by a similar amount. Since the interstitial compartment is about 3-fold larger than the plasma 5 compartment, K-loss from plasma accounts for only about 25% of the K-loss from the extracellular compartment.
