Internal Potassium Balance

Overview

Internal Potassium Balance refers to the distribution of total body potassium between the extracellular and intracellular fluid. Notably, 98% of the total body potassium exists within the intracellular fluid (ICF) whereas only 2% exists in the extracellular fluid (ECF). Rapid shifting of potassium into and out of the ICF is used as a critical mechanism for preventing large swings in the ECF and thus blood potassium concentration. Below we detail some disturbances which can lead to rapid changes in the extracellular potassium concentration and then discuss a variety of regulatory mechanisms that coordinate shifting of potassium between the ECF and ICF to buffer against short-term swings in the ECF potassium concentration.

Potassium Disturbances

Because the ECF potassium concentration is maintained at a low value the entire pool of ECF potassium may only be approximately 60 mEq. However, the average meal may contain roughly 40 mEq of potassium that is rapidly absorbed and added to the extracellular fluid by the alimentary tract. Therefore, this bolus of ingested potassium must be rapidly shifted into the intracellular space to prevent sharp spikes in ECF potassium with every ingestion of a meal.

As mentioned, cells possess enormous stores of potassium which can be released directly into the extracellular fluid in scenarios of rapid and massive cellular lysis as might occur during burns, rhabdomyolysis, hemolysis, or rapid lysis of tumor cells after induction of chemotherapy.

Skeletal muscle action potentials require large effluxes of intracellular potassium into the extracellular space. In contexts of strenuous exercise, the combined potassium efflux of many skeletal muscle cells can result in large movements of potassium into the extracellular space which must be buffered.

The vast majority of the body's cells contain an HK Antiporter which exchanges hydrogen ions (H⁺) with potassium ions (K⁺). As a consequence of this antiporter, ECF levels of potassium are often disturbed when the blood pH shifts.
Large increases in extracellular H⁺ concentration result in movement of hydrogen into cells and efflux of intracellular potassium into the extracellular fluid. Consequently, metabolic acidoses are often associated with hyperkalemia. As an aside, respiratory acidoses typically do not change the ECF potassium concentration because the built up acid (CO₂) can diffuse through the cell membrane itself and does not require transport through the antiporter.
Conversely, drops in extracellular H⁺ result in efflux of hydrogen from cells and influx of extracellular potassium into cells. Consequently, alkaloses are often associated with hypokalemia. For the same reasons as above, respiratory alkaloses are not associated with disturbances in potassium

Regulatory Mechanisms

A number of neuroendocrine mechanisms can modulate the shift and of potassium between the ICF and ECF.

Insulin promotes rapid cellular uptake of extracellular potassium by activating the NaK ATPase, thus shifting potassium from the ECF into the ICF. Release of insulin following a meal thus helps to shift potassium rapidly being added to the ECF by the alimentary tract into the intracellular fluid. The significance of this regulatory mechanism can be appreciated in patients with Type I Diabetes who can become hyperkalemic following a meal in the absence of proper insulin therapy.

Activation of the beta2 adrenergic receptor also stimulates the NaK ATPase and drives potassium into the ICF. As a result, beta2 adrenergic agonists such as albuterol and epinephrine can result in hypokalemia.

In addition to its effects on renal potassium excretion, aldosterone directly promotes cellular uptake of extracellular potassium, thus shifting potassium from the ECF into the ICF.

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