A Brief Review of the Pharmacology of Hyperkalemia: Causes and Treatment

James M. Wooten, PharmD; Fernanda E. Kupferman, MD; Juan C. Kupferman, MD, MPH


South Med J. 2019;112(4):228-233. 

In This Article

Potassium Physiology

The physiology of potassium in the body is complex. In humans, potassium is the most prevalent intracellular cation; approximately 98% of potassium exists within the cells, and the remaining 2% exists in the extracellular space. Along with sodium, chloride, and other electrolytes, potassium plays a key role in maintaining various homeostatic functions throughout the body. These anions and cations are used to maintain a specific extracellular-to-intracellular conduction gradient, which controls the electrical activity of various muscle types within the body, including the cardiac and skeletal muscles. High or low potassium concentrations can cause serious problems in maintaining the appropriate resting membrane potential and neuromuscular functioning. Excitatory tissue in the heart is particularly sensitive to significant variances in potassium concentrations.

The sodium/potassium-adenosine triphosphatase (Na+/K+-ATPase) pump regulates the influx of potassium into the myocyte and the efflux of sodium out of the cell. Changes in potassium levels within the body can cause problems with this enzyme system within the heart, which can lead to the development of serious cardiac arrhythmias. Hallmark electrocardiogram (ECG) changes indicative of hyperkalemia may include peaked T waves (tall and narrow), ST-segment depression, widening of the PR and QRS intervals (QT prolongation), and loss of the P wave. A sine-wave pattern on the ECG may signify impending ventricular fibrillation and asystole.[3,5–8]

A disrupted potassium balance also can affect skeletal and smooth muscle throughout the body. Inappropriate potassium concentrations can lead to overall muscle weakness, skeletal muscle paralysis, and hemodynamic instability. Potassium participates in several vital intracellular functions, including the acid–base balance, protein synthesis, and several enzymatic functions.

The body relies on several different mechanisms to maintain potassium homeostasis. The kidneys are responsible for regulating potassium balance because potassium can be reabsorbed or excreted as necessary. Much of the secretion and reabsorption of potassium takes place at the distal convoluted tubule and the proximal collecting duct. This action is primarily controlled by aldosterone, the primary hormone that can affect potassium homeostasis. Various situations (hypotension or hypertension), hormonal alterations (angiotensin II, cortisol, and insulin), and drugs can affect aldosterone secretion, thus influencing potassium balance.[5,6]

Appropriately monitoring and recognizing potential problems with potassium balance is key. In monitoring serum potassium levels, small changes in extracellular (serum or plasma) potassium concentrations may be reflective of major changes in intracellular potassium concentrations such that electrical activity across specific cellular membranes may be affected. It is unfortunate that the majority of patients who develop hyperkalemia are those with significant comorbidities, may be seriously ill, and the least likely to tolerate this abnormality.[7]