CE/CME

Hyperkalemia in Adults: Review of a Common Electrolyte Imbalance

Clinician Reviews. 2017 March;27(3):40-49

References

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Hyperkalemia is a common electrolyte disorder associated with life-threatening cardiac arrhythmias. Prompt recognition and appropriate treatment are essential in preventing serious cardiac complications. Although clinical manifestations of hyperkalemia are usually nonspecific or absent, laboratory testing and electrocardiography performed by the astute clinician aware of predisposing risk factors can help direct management.

Potassium is contained mostly in intracellular fluid; only about 2% is found in the extracellular space.¹ The average total body potassium is about 50 mEq per kg of body weight (eg, a 70-kg individual has a total body potassium of approximately 3,500 mEq).² Levels are tightly regulated by alterations in excretion in the distal renal tubule in response to potassium load and balance, and potassium distribution is influenced by insulin, aldosterone, catecholamines, and acid-base status.² Movement of potassium across cell membranes is driven by the sodium-potassium adenosine triphosphatase (Na-K-ATPase) pump.³ In this article, we use the common serum potassium reference range of 3.5 to 5.0 mEq/L and define hyperkalemia as a serum potassium concentration greater than 5.5 mEq/L.⁴

Hyperkalemia can lead to life-threatening complications of cardiac arrhythmias, asystole, hypotension, flaccid paralysis, tetany, dyspnea, and altered mental status.⁵ Among patients with end-stage renal disease (ESRD), hyperkalemia is thought to contribute to 2% to 5% of deaths.⁶ A retrospective study found that patients with serum potassium levels exceeding 6.0 mEq/L on ICU admission had a significantly higher death rate within 30 days than patients who were normokalemic on presentation.⁷

RISK FACTORS

It is estimated that more than 35% of patients age 70 and older have chronic kidney disease (CKD) stage 3 or higher.⁸ Hyperkalemia is closely associated with CKD, increasing linearly in relation to the degree of renal impairment.⁸ As such, the prevalence of hyperkalemia in older adults is high, and it will increase overall as the US population ages. In a retrospective analysis of veterans older than 65 with CKD stage 3 or higher, the prevalence of hyperkalemia was 2.5%.⁹ Use of certain medications is also associated with hyperkalemia. Another retrospective study analyzed records obtained from 70,873 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m²) hospitalized in the Veterans Health Administration system. It found that patients treated with renin-angiotensin-aldosterone system (RAAS) blockers, such as ACE inhibitors (ACEis) or angiotensin-receptor blockers (ARBs), had a higher incidence of hyperkalemia (potassium level ≥ 5.5 mEq/L) than patients not treated with these medications (8.22 vs 1.77 events per 100 patient-months).^9,10

POTASSIUM HOMEOSTASIS

Tight control over extracellular potassium is maintained in part by the Na-K-ATPase pump, which uses adenosine triphosphatase to move potassium and sodium ions in opposite directions across cell membranes.³ Specifically, three sodium ions are pumped out of the cell for every two potassium ions pumped in, resulting in a potassium gradient that is partially responsible for maintaining a resting membrane potential. This resting membrane potential, which determines myocardial, skeletal muscle, and nerve cell excitability and signaling, is highly sensitive to changes in the extracellular potassium level.⁴ Even small extracellular imbalances can induce cell depolarization and evoke an action potential. Increased extracellular potassium concentration decreases the resting membrane potential of the myocardium, shortens repolarization time, and decreases the rate of myocardial cell conduction, and also slows down neuromuscular conduction.^11,12

Renal tubular function plays a significant role in potassium homeostasis, with approximately 90% of dietary potassium intake excreted through the urine. Another 5% to 10% of potassium excretion is via the gut, and the remainder leaves the body through sweat.⁴ Potassium is filtered in the kidney’s glomerulus and mostly reabsorbed in the proximal tubule and the loop of Henle; 10% of the filtered load reaches the distal nephron, where it is secreted into the collecting ducts to be excreted through urination.^13,14

The RAAS is a signal transduction pathway that regulates potassium excretion by the kidneys. Renin is secreted by the kidney in response to low renal perfusion, catecholamines, ß-adrenergic stimulation, potassium and sodium levels, and other factors. Secretion of renin triggers a signaling cascade that eventually results in the release of aldosterone from the adrenal cortex.⁵ Aldosterone binds to a receptor in the kidney’s collecting ducts where it increases potassium excretion by stimulating sodium reabsorption and fluid retention (see Figure 1).⁵

CAUSES OF HYPERKALEMIA

The pathophysiology of hyperkalemia generally involves either decreased renal excretion or shifts in extracellular potassium. Causes of hyperkalemia are listed in the Table. Potassium excretion can be disrupted in acute kidney injury (AKI), sepsis, cardiac ischemia, heart failure, diabetic ketoacidosis (DKA), insulin deficiency, tumor lysis syndrome (TLS), sickle cell disease, systemic lupus erythematosus, renal transplant, hepatorenal syndrome, adrenal insufficiency, and obstructive uropathy.¹⁵ In addition, certain medications can impair potassium excretion (eg, RAAS blockers, potassium-sparing diuretics in patients with CKD, digoxin toxicity).¹⁶ The following sections highlight the pathophysiology and manifestations of more common causes of hyperkalemia.