• Clinical science

Disorders of potassium balance

Summary

Potassium disorders may take the form of hyperkalemia (high serum potassium) or hypokalemia (low serum potassium). The most common cause of hyperkalemia is decreased kidney function. It may also be caused by endocrinological disturbances (e.g., hypoaldosteronism, hypocortisolism) or drugs such as potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), and digoxin. Low serum potassium levels, on the other hand, can be caused by gastrointestinal losses (e.g., due to vomiting, diarrhea) or drugs such as non-potassium-sparing diuretics and laxatives. To determine the cause of a potassium disorder, it is essential to review the patient's medications and test for aldosterone and cortisol disturbances. Acute changes in serum potassium are very dangerous, as they influence the resting membrane potential and thus the electrical excitability of cells. These changes can lead to malignant cardiac arrhythmias. The management of hypokalemia and hyperkalemia includes dietary changes, medications, and, in the case of hyperkalemia, dialysis. The potassium serum concentration should be monitored closely until it is corrected.

Hyperkalemia

Definition

  • Serum potassium level > 5 mEq/L [1]

Etiology

  1. Potassium excess
  2. Extracellular shift
    • Acidosis → ↑ extracellular H+inhibition of the Na+/H+ antiporter↓ intracellular Na+↓ sodium gradient inhibits the Na+/K+-ATPase↑ extracellular K+ concentration
      • Hyperkalemia ↑ extracellular K+ concentration → ↑ potassium gradient stimulates the Na+/K+-ATPase↑ extracellular Na+↑ sodium gradient stimulates the Na+/H+ antiporter↑ extracellular H+acidosis
      • Exception: In renal tubular acidosis, findings include hypokalemia and metabolic acidosis.
    • Insulin deficiency
    • Drugs: succinylcholine; , digoxin
  3. Pseudohyperkalemia: due to the release of potassium from red blood cell lysis
    • Blood drawn from the side of IV infusion or a central line without previous flushing
    • Prolonged use of a tourniquet

K+ acts like H+ → Hyperkalemia leads to acidosis and vice versa! Hypokalemia leads to alkalosis and vice versa!

Errors in blood drawing technique may lead to red blood cell lysis and a falsely elevated serum potassium concentration (pseudohyperkalemia)!

References:[4][1][3][2][5]

Pathophysiology

Potassium is an important factor in maintaining the resting membrane potential

  • ↑ Extracellular K+ concentration → ↓ resting membrane potential (less negative than -90 mV) → ↑ excitability

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

Clinical features

Symptoms usually occur if serum potassium levels are > 7.0 mEq/L or they change rapidly.

Hyperkalemia as well as Hypokalemia can cause cardiac arrhythmia and may lead to ventricular fibrillation!

References:[6][1][7][8]

Diagnostics

References:[6][1]

Treatment

  • Potassium level ≤ 6.5 mEq/L and no signs of cardiotoxicity: decrease intake/absorption (slow-acting option)
    • Discontinue drugs that increase serum potassium
    • Avoid high-potassium foods
    • Cation-exchange resins (e.g., sodium polystyrene sulfonate): bind potassium in the gut via the exchange of Na+ for K+
      • Adverse effect (rare): intestinal necrosis
    • Loop diuretics: promote excretion of potassium and lower total body potassium stores
    • Intravenous, non potassium containing fluids: normal saline, dextrose 5% in water
  • Potassium level > 6.5 mEq/L or cardiotoxicity: IV therapy for cardioprotection and to induce elimination/intracellular shift (rapid-acting option)
    • Calcium gluconate: should be administered first!
    • Insulin and glucose
    • Sodium bicarbonate: in acidemic patients
    • Beta-2-adrenergic agonists
    • Forced diuresis (loop diuretics with normal saline solution)
  • Renal failure or ineffective initial treatment
    • Hemodialysis: most effective and definitive treatment option


References:[9][10]

Hypokalemia

Definition

  • Serum potassium level < 3.5 mEq/L [11]

Etiology

  • Potassium loss
    • Renal loss
      • Endocrine causes: hyperaldosteronism, hypercortisolism
      • Drugs: diuretics, glucocorticoids, licorice (aldosterone-like action)
      • Hypomagnesemia
      • (1) Since magnesium serves as a cofactor in Na+-K+-ATPases, hypomagnesemia disrupts the Na+-K+-ATPase in the basolateral membrane of the cells of the proximal convoluted tubule and loop of Henle, leading to decreased Na+ reabsorption. This causes increased luminal sodium that, distally, leads to increased sodium reabsorption and potassium secretion by the principal cell; and (2) Apical ROMK channels in principal cells are inhibited by intracellular magnesium. With low levels of magnesium available, the ROMK channels are not inhibited, so K+ secretion increases.

      • Type I and II renal tubular acidosis
    • Gastrointestinal loss: vomiting, diarrhea, laxatives (e.g., in bowel preparation prior to medical procedures)
  • Intracellular shift
    • Alkalosis ↓ extracellular H+ → stimulation of the Na+/H+ antiporter (transfers H+ out of the cells in exchange for Na+) → ↑ intracellular Na+↑ sodium gradient stimulates the Na+/K+-ATPase (transfers K+ into the cells in exchange for Na+) → ↓ extracellular K+ concentration
      • Hypokalemia↓ extracellular K+ concentration → ↓ potassium gradient inhibits the Na+/K+-ATPase↓ extracellular Na+↓ sodium gradient inhibits the Na+/H+ antiporter↓ extracellular H+alkalosis
      • Exception: In renal tubular, acidosis findings include hypokalemia and metabolic acidosis!
    • Insulin therapy
    • β2-mediated stimulation of Na+/K+-ATPase

K+ acts like H+ → Hyperkalemia leads to acidosis and vice versa! Hypokalemia leads to alkalosis and vice versa!

"Potassium follows glucose into the cells!": (i)nsulin → (i)ntracellular K+

References:[4][12][13]

Pathophysiology

Potassium is an important factor in maintaining the resting membrane potential

  • ↓ Extracellular K+ concentration → ↑ resting membrane potential (more negative than -90 mV) → ↓ excitability

Particularly acute extracellular changes in concentration influence excitability! Chronic changes lead to intracellular compensation!

Clinical features

Symptoms usually occur if serum potassium levels are < 3.0 mEq/L or they change rapidly.

Hyperkalemia as well as Hypokalemia can cause cardiac arrhythmia and may lead to ventricular fibrillation!

References:[6][14]

Diagnostics

  • Laboratory evaluation
    • Serum potassium levels (always confirm abnormal serum potassium levels with a repeat blood draw)
    • Urinary potassium level
      • > 20 mEq/L: renal loss
      • < 20 mEq/L: extrarenal loss
    • Arterial blood gas (ABG): influence of pH on the potassium homeostasis
  • ECG changes
    • Presence of U waves; possibly TU fusion; premature atrial and ventricular complexes
    • ST depression
    • T-wave flattening

"No pot, no tea!" → A lack of potassium may result in a flattened T wave.

References:[6][11]

Treatment

IV potassium may cause vein damage and lead to cardiac arrhythmias. Therefore, it should always be administered slowly (max. rate of 22 mEq/h)!

References:[6][10]

Periodic paralysis

Definition

Periodic paralyses comprises a group of muscle diseases that are characterized by weakness (proximal, symmetric, flaccid paralysis) with a simultaneous drop or rise in potassium levels.

Etiology

Mode of inheritance: autosomal-dominant inheritance with complete penetrance

Pathophysiology

  • Symptoms are triggered by hypo- or hyperkalemia:
    • Hypokalemia: change in membrane permeability to potassium → extracellular potassium deficiency and intracellular sodium deficiency → refractory muscle tissue
    • Hyperkalemia: defect in sodium channels → sodium channels remain open → membrane repolarization is impaired

Periodic paralysis may be associated with hyperkalemia or hypokalemia.

Hyperkalemic periodic paralysis

Hyperkalemic periodic paralysis is caused by a genetic defect affecting the voltage-gated sodium channel.

Hypokalemic periodic paralysis

Hypokalemic periodic paralysis may be caused by a genetic defect affecting one or all of the following three ion channels:

Clinical features

Hypokalemic periodic paralysis

  • Proximal, symmetric, flaccid paralysis and areflexia; Symptoms appear early in the morning hours and in the evening.
  • Paralysis may last for hours to days and may involve respiratory muscles.
  • Triggers: a carbohydrate-rich meal, a rise in insulin levels , hyperthyroidism

Hyperkalemic periodic paralysis

  • Hyperkalemic periodic paralysis is generally less severe than the hypokalemic form; respiratory muscles are spared while facial and pharyngeal muscles are often involved.
  • Paralysis may last for minutes to hours
  • Triggers: small fluctuations in potassium levels, exposure to cold, physical exertion

Diagnostics

  • Neurological examination: flaccid paralysis, areflexia
  • EMG: low-amplitude muscle potentials
  • EKG: U-wave in the case of hypokalemia, peaked T-wave in the case of hyperkalemia
  • Laboratory findings: serum potassium levels < 3.5 mmol/L (hypokalemia) or > 5.5 mmol/L (hyperkalemia)

Treatment

  • During a spell of periodic paralysis:
    • Hypokalemic periodic paralysis: potassium chloride, acetazolamide (an episode of hypokalemic periodic paralysis can be lethal!)
    • Hyperkalemic periodic paralysis: calcium gluconate