Why hypokalemia causes tachycardia

Principles of Critical Care, 4e >

Potassium is the most common cation in the body.Normal serum potassium ranges from 3.5 to 5.2 mmol/L. The molecular weight of potassium is 39.1, so a daily potassium intake of 80 mmol is roughly equivalent to 3.1 g of potassium.

The normal physiologic handling of potassium can be viewed as a three-step process: 

1. ingestion
2. cellular distribution
3. excretion

Irregularities at any of these steps can result in pathologic serum potassium concentrations.

Cell Uptake: Following absorption, potassium distributes among the intracellular and extracellular compartments. The intracellular compartment acts as the primary buffer to changes in serum potassium concentration.

The Na-K-ATPase pump, driven by a ubiquitous cell surface enzyme, moves potassium into cells while pumping sodium out of cells. The pump is stimulated by β2-adrenergic activity, while α-adrenergic activity results in potassium efflux.53 Insulin also stimulates the activity of this pump and is independent of its hypoglycemic activity.54

Extracellular pH can affect the cellular distribution of potassium. Various explanations have been proposed, including a direct effect of pH on the Na-K-ATPase, or an H+-K+exchange to maintain electroneutrality. The effect of pH on potassium distribution varies depending on the nature of the acid-base disturbance. Respiratory acidosis, alkalosis, and organic acidosis all have minimal effect on potassium distribution. Inorganic acidosis can increase serum potassium, while metabolic alkalosis can lower potassium. Inorganic acidosis  (ie, non-Anion Gap). Diabetic ketoacidosis (DKA) often presents with hyperkalemia that does not parallel the acidosis; in this case, hyperkalemia results from insulin deficiency and the effects of hyperosmolality. Lactic acidosis and other forms of organic acidosis generally do not present with a significant potassium shift.

Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L, and is found among 20% of the hospitalized population. However, this high frequency probably does not reflect total body potassium depletion. In a review of 70 hospitalized patients with a potassium less than 2.8 mmol/L, the potassium rose toward normal regardless if they were given potassium or not. The authors suggested that hospitalization for acute illness was associated with increased adrenergic stimulation, resulting in intracellular movement of potassium and transient hypokalemia.60

Hyperkalemia is defined as a serum potassium concentration above 5.2 mmol/L

Increased Potassium Intake is one cause; e.g., KCl salt substitute

Transfusion of red blood cells

Intracellular Redistribution of Potassium - The Na-K-ATPase is critical in preventing intracellular potassium from causing hyperkalemia. Any factor that decreases the activity of this enzyme will cause potassium to leak from cells. A lack of insulin slows the Na-K-ATPase. In diabetic ketoacidosis hyperkalemia is typical.  β-Blockers inhibit the Na-K-ATPase activity and are associated with a mild increase in serum potassium. Uremia reduces Na-K-ATPase activity so that renal failure patients are less able to use the intracellular compartment to buffer potassium loads. Digitalis is an Na-K-ATPase antagonist. Digitalis toxicity can cause severe hyperkalemia.

Inorganic acids increase serum potassium. Decreases in pH due to respiratory or organic acidosis (e.g., lactic acidosis) have minimal effect on serum potassium.

Clinical Sequelae: The potassium concentrations inside and outside of the cell are the primary determinants of the cellular resting membrane potential (Em). Changes in the extracellular concentration can have dramatic effects on the resting membrane potential and the cell’s ability to depolarize. As extracellular potassium rises, the normally negative Em increases toward zero; this allows easier depolarization (ie, increased excitability). However, this excitability is short-lived as chronic hyperkalemia ultimately inactivates the sodium channels critical to producing an action potential. Hyperkalemia shortens the refractory period following depolarization by facilitating faster potassium uptake.

In the myocardium, inactivated sodium channels slow conduction velocity, and high serum potassium speeds repolarization. On ECG, hyperkalemia causes widened QRS complexes (slowed conduction velocity) and shortened ST intervals with tented T waves (rapid repolarization). The slowed conduction associated with rapid repolarization predisposes the myocardium to ventricular fibrillation.

During Phase 4 there is also a slow decline in the outward movement of K⁺ as the K⁺ channels responsible for Phase 3 continue to close. This fall in K⁺ conductance (gK⁺) contributes to the depolarizing pacemaker potential.

Hypokalemia increases the rate of phase 4 depolarization and causes tachycardia.  It apparently does this by decreasing gK during phase 4.

E_m = g'_K E_K  + ..................

The effects of hyperkalemia and hypokalemia on heart rate are explained by changes in membrane conductance rather than by changes in the potassium Nernst potential.  The increase in K conductance that occurs in hyperkalemia causes the maximum diastolic potential (MDP) to shift closer to EK. Accordingly, even though EK becomes more positive in hyperkalemia, the MDP becomes more negative.  This negative shift in MDP acts to slow heart rate by increasing the potential difference between MDP and the threshold for activation of the L-type calcium current.  In addition, the increased K conductance that occurs in hyperkalemia makes it more difficult for the funny sodium current to drive phase 4 depolarization.  Heart rate is also slowed by a decrease in the rate of phase 4 depolarization.   Just the opposite effects are produced by the decreased K conductance associated with hypokalemia.  The decreased conductance causes MDP to become more positive even though EK becomes more negative.  In addition, the decreased K conductance allows the funny sodium current to be more effective at driving phase 4 depolarization which results in a faster phase 4 depolarization.