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Potassium is the principal cation of the intracellular fluid (ICF) where its concentration is between 120 and 150 mEq/L. The extracellular fluid (ECF) and plasma potassium concentration [K] is much lower—in the 3.5- to 5-mEq/L range. This very large transcellular gradient is maintained by active K transport via the Na/K ATPase pumps present in all cell membranes and the ionic permeability characteristics of these membranes. The resulting 30–40 fold transmembrane [K] gradient is the principal determinant of the transcellular resting potential gradient, which is about 90 mV, with the cell interior negative (Figure 4–1). Normal cell function requires maintenance of the ECF [K] within a relatively narrow range. This is particularly important for excitable cells such as myocytes, conducting tissues, and neurons. The pathophysiologic effects of hypokalemia and hyperkalemia on these cells result in most of the clinical manifestations.

Figure 4–1.

Transcellular ion movement. Most cells contain these pumps, antiporters, and channels. The effects of insulin, catecholamines, and thyroid hormones on K transport are shown.

Individual potassium intakes vary widely—a typical western diet provides between 50 and 100 mEq K/day and about 90% of the ingested K is absorbed by the gastrointestinal (GI) tract. Under steady-state conditions, an equal amount is lost from the body. Most is excreted in urine and a small amount in stool and sweat. Homeostatic mechanisms maintain plasma [K] between 3.5 and 5.0 mEq/L. A large ingested meal may contain more potassium than is present in the entire ECF. Yet the serum K concentration generally varies by less than 10%. This homeostasis is achieved by the integrated action of multiple regulatory systems. The normal postprandial rise in insulin concentration drives both K and glucose into the intracellular compartment. Although postprandial insulin release is primarily stimulated by increased plasma glucose concentrations, potassium also directly stimulates pancreatic β-cells to release insulin. Insulin deficiency and/or resistance can increase plasma [K]. In addition a postprandial “feed-forward” system, which is not yet fully understood, increases urine K excretion in response to oral K loads independent of changes in serum K or known K regulating hormones. Urine K excretion also has a circadian rhythm component. Epinephrine and norepinephrine also rapidly regulate transcellular K balance and become especially important during and following vigorous exercise. Hyperadrenergic states such as alcohol withdrawal and hyperthyroidism, β-sympathomimetics such as the tocolytic terbutaline, and theophylline poisoning can generate hypokalemia due to translocation of K from the ECF into cells.

Hyperchloremic acidosis (and other inorganic or mineral acidoses) shifts K out of cells. However, the much more common organic metabolic acidoses (lactic and ketoacidosis) do not directly generate much K shift. Both respiratory acidosis and respiratory alkalosis generate some K shift from cells to the ECF. It had been assumed that the alkalemia produced by respiratory alkalosis would drive K into cells, but studies found that the opposite ...

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