Hyperkalemia

Hyperkalemia is a condition characterized by elevated levels of potassium in the blood. It is a potentially life-threatening electrolyte imbalance that can lead to neuromuscular and cardiac complications. Prompt recognition and management are critical to prevent severe outcomes.

Introduction

Potassium is a key intracellular cation involved in maintaining resting membrane potential, neuromuscular function, and cardiac rhythm. Hyperkalemia occurs when serum potassium exceeds the normal range, typically above 5.0 mmol/L. The severity of hyperkalemia depends on both the absolute potassium level and the rate of increase.

Etiology

Increased Potassium Intake

• Dietary Excess: Rarely causes hyperkalemia in patients with normal renal function but can contribute in those with impaired excretion.
• Potassium Supplements: Excessive oral or intravenous potassium can precipitate hyperkalemia, especially in at-risk individuals.

Decreased Renal Excretion

• Acute Kidney Injury: Impaired renal function reduces potassium clearance.
• Chronic Kidney Disease: Progressive nephron loss leads to potassium retention.
• Hypoaldosteronism: Conditions such as Addison’s disease decrease renal potassium excretion.

Cellular Shift of Potassium

• Metabolic Acidosis: Hydrogen-potassium exchange shifts potassium from intracellular to extracellular space.
• Insulin Deficiency: Reduced cellular uptake of potassium, as seen in uncontrolled diabetes.
• Tissue Breakdown: Rhabdomyolysis, hemolysis, and tumor lysis syndrome release intracellular potassium into the bloodstream.

Medications

• Potassium-Sparing Diuretics: Spironolactone, eplerenone, and amiloride can reduce renal potassium excretion.
• ACE Inhibitors and ARBs: Inhibit aldosterone production and promote potassium retention.
• NSAIDs and Other Drugs: Can impair renal potassium handling and contribute to hyperkalemia.

Pathophysiology

Potassium Homeostasis

Potassium homeostasis is primarily maintained by renal excretion and cellular uptake. The kidneys regulate potassium through filtration, reabsorption, and secretion in the distal nephron. Aldosterone plays a key role by promoting sodium reabsorption and potassium excretion.

Mechanisms of Hyperkalemia

• Extracellular Shift: Conditions such as acidosis, insulin deficiency, and tissue breakdown lead to potassium moving from cells into the bloodstream.
• Impaired Renal Excretion: Kidney dysfunction, hypoaldosteronism, or medication effects reduce the ability to eliminate potassium.

Cardiac Electrophysiology

Elevated extracellular potassium alters the resting membrane potential of cardiac myocytes, resulting in slower conduction and increased risk of arrhythmias. Severe hyperkalemia can lead to ventricular fibrillation and cardiac arrest if not treated promptly.

Clinical Manifestations

General Symptoms

• Fatigue and malaise
• Muscle weakness
• Paresthesia or numbness

Neuromuscular Effects

• Muscle cramps and stiffness
• Progressive flaccid paralysis in severe cases
• Reduced reflexes

Cardiac Manifestations

• Palpitations and skipped beats
• Bradycardia or tachyarrhythmias
• Risk of life-threatening arrhythmias

Laboratory Diagnosis

Serum Potassium Measurement

Measurement of serum potassium is the primary method for diagnosing hyperkalemia. Values above 5.0 mmol/L indicate hyperkalemia, with higher levels correlating with increased risk of complications.

Electrolyte Panel

• Assessment of sodium, bicarbonate, calcium, and magnesium is important to identify concurrent electrolyte disturbances.
• Evaluation helps guide management and detect underlying causes such as acidosis or hypocalcemia.

Renal Function Tests

• Serum creatinine and blood urea nitrogen (BUN) assess kidney function and the ability to excrete potassium.
• Impaired renal function is a common contributor to hyperkalemia.

Other Relevant Tests

• Arterial blood gas analysis to evaluate acid-base status.
• Markers of hemolysis or tissue breakdown, such as lactate dehydrogenase (LDH) and creatine kinase (CK), to detect intracellular potassium release.

Electrocardiographic Findings

• Peaked T waves, especially in precordial leads, often the earliest ECG change.
• Prolongation of PR interval and flattening of P waves as hyperkalemia progresses.
• Widening of the QRS complex, which may merge with T waves forming a sine wave pattern in severe cases.
• Risk of ventricular fibrillation or asystole if untreated.

Severity Classification

Hyperkalemia is classified based on serum potassium levels and associated clinical findings. Severity guides urgency and management strategies.

• Mild Hyperkalemia: Serum potassium 5.1–5.9 mmol/L; usually asymptomatic or mild neuromuscular symptoms.
• Moderate Hyperkalemia: Serum potassium 6.0–6.9 mmol/L; may present with muscle weakness and ECG changes.
• Severe Hyperkalemia: Serum potassium ≥7.0 mmol/L; associated with significant neuromuscular impairment and high risk of life-threatening cardiac arrhythmias.

Differential Diagnosis

It is important to distinguish true hyperkalemia from conditions or artifacts that falsely elevate serum potassium levels.

• Pseudohyperkalemia: Elevated potassium due to hemolysis during blood sample collection or prolonged tourniquet use.
• Laboratory Errors: Sample handling or analyzer inaccuracies can cause spurious results.
• Other Causes of Hyperkalemia: Conditions such as acidosis, medications, or tissue breakdown must be considered in the differential.

Management

Immediate Measures

• Continuous cardiac monitoring for patients with significant hyperkalemia.
• Intravenous calcium gluconate to stabilize cardiac membranes and reduce arrhythmia risk.

Shift of Potassium into Cells

• Intravenous insulin with glucose to promote cellular uptake of potassium.
• Beta-2 agonists, such as nebulized albuterol, can drive potassium into cells.
• Sodium bicarbonate may be used in patients with metabolic acidosis to shift potassium intracellularly.

Removal of Potassium

• Loop or thiazide diuretics to enhance renal potassium excretion.
• Sodium polystyrene sulfonate or newer potassium binders for gastrointestinal potassium removal.
• Hemodialysis in severe or refractory cases, especially in renal failure.

Medication Review

• Discontinue or adjust drugs that contribute to hyperkalemia, including potassium-sparing diuretics, ACE inhibitors, ARBs, and NSAIDs.

Prevention

Dietary Counseling

• Educate high-risk patients on limiting high-potassium foods.
• Provide guidance on safe potassium intake in chronic kidney disease or other predispositions.

Monitoring in High-Risk Patients

• Regular serum potassium measurement in patients with renal impairment or those taking potassium-retaining medications.
• Early detection of rising potassium levels allows timely intervention.

Medication Adjustments

• Use alternatives to potassium-sparing medications when appropriate.
• Adjust doses of ACE inhibitors or ARBs based on renal function and potassium levels.

Prognosis

The prognosis of hyperkalemia depends on the severity, underlying cause, and promptness of treatment. Mild hyperkalemia often resolves with dietary or medication adjustments, whereas severe cases carry a high risk of cardiac complications.

• Early recognition and treatment significantly reduce morbidity and mortality.
• Patients with underlying renal dysfunction or severe comorbidities may have prolonged recovery and increased risk of recurrence.
• Untreated severe hyperkalemia can lead to fatal arrhythmias and sudden cardiac arrest.

References

1. Palmer BF, Clegg DJ. Electrolyte and acid-base disturbances in chronic kidney disease. N Engl J Med. 2015;372(1):79-81.
2. Weiner ID, Wingo CS. Hyperkalemia: evaluation and management. Am J Kidney Dis. 1998;32(3):566-571.
3. Einbinder JS, Rahman M. Hyperkalemia. N Engl J Med. 2017;377(4):395-396.
4. Gennari FJ. Disorders of potassium homeostasis. Hypokalemia and hyperkalemia. Crit Care Clin. 2002;18(2):273-288.
5. Montford JR, Linas S. How dangerous is hyperkalemia? J Am Soc Nephrol. 2017;28(11):3155-3165.
6. Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351(6):585-592.
7. Mahoney BA, Alpern RJ. Hyperkalemia: pathophysiology, diagnosis, and treatment. J Am Soc Nephrol. 1997;8(11):1745-1754.
8. McMahon EJ, Frazer LH. Hyperkalemia: an overview. Intern Med J. 2011;41(1a):6-12.
9. Goldberg A, Kamel KS. The management of hyperkalemia. Kidney Int. 2010;77(4):321-329.
10. Graded, RH, et al. Hyperkalemia: diagnosis and treatment. Am Fam Physician. 2019;99(1):32-39.