What are the causes and treatments of electrolyte disorders, including potassium (K+), sodium (Na+), calcium (Ca2+), magnesium (Mg2+), chloride (Cl-), and phosphate (PO4) imbalances?

Causes and Treatment of Electrolyte Disorders

Electrolyte disorders require prompt identification and correction to prevent serious complications including cardiac arrhythmias, seizures, coma, and death. Understanding the pathophysiology, causes, and appropriate treatment approaches for each electrolyte imbalance is essential for optimal patient management.

Potassium (K+) Disorders

Hyperkalemia (K+ > 5.5 mEq/L)

Causes:

• Decreased renal excretion: CKD, AKI, adrenal insufficiency, type 4 RTA
• Medication-induced: RAASi (ACE inhibitors, ARBs), potassium-sparing diuretics, NSAIDs, trimethoprim
• Cellular shifts: Acidosis, insulin deficiency, beta-blockers, digoxin toxicity
• Excessive intake: Potassium supplements, salt substitutes, blood transfusions
• Pseudohyperkalemia: Hemolysis, thrombocytosis, leukocytosis

Treatment:

1. Severe (K+ > 6.5 mEq/L or ECG changes):

   • Calcium gluconate 10% (10 mL IV over 2-3 min) for cardiac membrane stabilization
   • Insulin (10 units regular) with glucose (25-50g) IV to shift K+ intracellularly
   • Albuterol nebulization (10-20 mg)
   • Sodium bicarbonate (50 mEq IV) if acidotic
   • Emergency dialysis if life-threatening or refractory

2. Moderate (K+ 6.0-6.5 mEq/L):

   • Sodium polystyrene sulfonate or newer K+ binders (patiromer, sodium zirconium cyclosilicate)
   • Loop diuretics if kidney function adequate
   • Discontinue offending medications

Hypokalemia (K+ < 3.5 mEq/L)

Causes:

• Decreased intake: Malnutrition, anorexia
• Increased losses: Vomiting, diarrhea, diuretics, laxative abuse
• Renal losses: Hyperaldosteronism, RTA, magnesium deficiency, Bartter/Gitelman syndromes
• Cellular shifts: Alkalosis, insulin, beta-agonists, periodic paralysis

Treatment:

• Mild (K+ 3.0-3.5 mEq/L): Oral potassium chloride 40-80 mEq/day in divided doses 1
• Moderate (K+ 2.5-3.0 mEq/L): Oral potassium chloride 80-120 mEq/day in divided doses 1
• Severe (K+ < 2.5 mEq/L): IV potassium at 10-20 mEq/hour (not exceeding 40 mEq/hour in critical situations) with continuous cardiac monitoring 1
• Correct underlying cause and magnesium deficiency if present

Sodium (Na+) Disorders

Hyponatremia (Na+ < 135 mEq/L)

Classification by Volume Status:

1. Hypovolemic hyponatremia:

   • Causes: GI losses, diuretics, adrenal insufficiency, cerebral salt wasting
   • Treatment: Isotonic saline (0.9% NaCl) at 4-14 ml/kg/hour based on severity 1, 2

2. Euvolemic hyponatremia:

   • Causes: SIADH, hypothyroidism, psychogenic polydipsia, medications
   • Treatment: Fluid restriction (<1 L/day), address underlying cause, consider vasopressin receptor antagonists 2, 3

3. Hypervolemic hyponatremia:

   • Causes: Heart failure, cirrhosis, nephrotic syndrome, renal failure
   • Treatment: Fluid restriction, diuretics, treat underlying condition 2

4. Severe symptomatic hyponatremia (Na+ < 120 mEq/L with neurological symptoms):

   • Treatment: 3% hypertonic saline at 1-2 ml/kg/hour
   • Do not exceed correction rate of 8-10 mEq/L in 24 hours or 0.5-1 mEq/L/hour 1

Hypernatremia (Na+ > 145 mEq/L)

Causes:

• Water loss: Diabetes insipidus, excessive sweating, fever, diarrhea
• Inadequate water intake: Altered mental status, lack of access to water
• Sodium gain: Hypertonic saline, sodium bicarbonate, primary hyperaldosteronism

Treatment:

• Replace free water deficit with hypotonic fluids (0.45% NaCl or D5W)
• Correction rate should not exceed 10 mEq/L/24 hours to prevent cerebral edema
• Address underlying cause

Calcium (Ca2+) Disorders

Hypercalcemia (Ca2+ > 10.5 mg/dL)

Causes:

• Primary hyperparathyroidism
• Malignancy (PTHrP, bone metastases)
• Vitamin D toxicity
• Granulomatous diseases (sarcoidosis, TB)
• Medications (thiazides, lithium)

Treatment:

• Mild to moderate: Oral hydration, discontinue offending medications
• Severe (Ca2+ > 14 mg/dL or symptomatic):
  • IV normal saline (200-300 mL/hour)
  • Bisphosphonates (zoledronic acid 4 mg IV or pamidronate 60-90 mg IV)
  • Calcitonin 4-8 IU/kg SC/IM q12h
  • Consider hemodialysis in refractory cases

Hypocalcemia (Ca2+ < 8.5 mg/dL)

Causes:

• Hypoparathyroidism (surgical, autoimmune)
• Vitamin D deficiency
• Chronic kidney disease
• Pancreatitis
• Medications (bisphosphonates, anticonvulsants)
• Hypomagnesemia

Treatment:

• Symptomatic or severe: Calcium gluconate 10% (1-2 ampules IV over 10-20 min)
• Chronic management: Oral calcium supplements (1-3 g/day) and vitamin D
• Correct hypomagnesemia if present

Magnesium (Mg2+) Disorders

Hypermagnesemia (Mg2+ > 2.5 mg/dL)

Causes:

• Renal failure
• Excessive intake (antacids, laxatives)
• Adrenal insufficiency

Treatment:

• Discontinue magnesium-containing medications
• IV calcium gluconate for cardiac protection
• Hemodialysis in severe cases

Hypomagnesemia (Mg2+ < 1.8 mg/dL)

Causes:

• GI losses (diarrhea, malabsorption)
• Alcoholism
• Medications (diuretics, proton pump inhibitors, aminoglycosides)
• Refeeding syndrome

Treatment:

• Mild (1.2-1.7 mg/dL): Oral magnesium oxide/citrate 400-800 mg/day in divided doses 1
• Moderate (0.8-1.2 mg/dL): Oral magnesium 800-1600 mg/day in divided doses 1
• Severe (<0.8 mg/dL): IV magnesium sulfate 1-2 g over 1 hour, followed by 0.5-1 g every 6 hours 1

Phosphate (PO4) Disorders

Hyperphosphatemia (PO4 > 4.5 mg/dL)

Causes:

• Renal failure
• Tumor lysis syndrome
• Rhabdomyolysis
• Excessive intake (laxatives, enemas)
• Hypoparathyroidism

Treatment:

• Dietary phosphate restriction
• Phosphate binders (calcium acetate, sevelamer, lanthanum)
• Dialysis in severe cases

Hypophosphatemia (PO4 < 2.5 mg/dL)

Causes:

• Refeeding syndrome
• Alcoholism
• Diabetic ketoacidosis
• Respiratory alkalosis
• Malnutrition
• Intensive/prolonged KRT 4

Treatment:

• Mild (2.0-2.5 mg/dL): Oral phosphate 1000-2000 mg/day in divided doses 1
• Moderate (1.0-2.0 mg/dL): Oral phosphate 2000-3000 mg/day in divided doses 1
• Severe (<1.0 mg/dL): IV phosphate 0.08-0.16 mmol/kg over 4-6 hours 1

Chloride (Cl-) Disorders

Hyperchloremia (Cl- > 107 mEq/L)

Causes:

• Dehydration
• Renal tubular acidosis
• Excessive normal saline administration
• Diarrhea

Treatment:

• Address underlying cause
• Switch from normal saline to balanced crystalloids if iatrogenic

Hypochloremia (Cl- < 98 mEq/L)

Causes:

• Vomiting, nasogastric suction
• Diuretics
• Metabolic alkalosis
• SIADH

Treatment:

• Correct underlying cause
• Normal saline administration if symptomatic

Special Considerations

Refeeding Syndrome

• High risk in malnourished patients when nutrition is reintroduced
• Can cause severe hypophosphatemia, hypokalemia, hypomagnesemia
• Prevention: Start feeding at low levels (10 kcal/kg/day) while providing generous electrolyte supplementation 4

Electrolyte Management in Kidney Replacement Therapy

• Close monitoring of electrolytes is essential in patients receiving KRT 4
• Common abnormalities: hypophosphatemia, hypokalemia, hypomagnesemia
• Electrolyte supplementation should be individualized based on KRT modality and intensity

Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State

• Requires careful monitoring and replacement of potassium, phosphate, and magnesium
• Initial fluid therapy with isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour 4
• Once renal function is assured, include 20-30 mEq/L potassium in maintenance fluids 4

Pitfalls and Caveats

1. Rapid correction of sodium disorders can lead to osmotic demyelination syndrome (too fast correction of hyponatremia) or cerebral edema (too fast correction of hypernatremia)

2. Refeeding syndrome can be fatal if not anticipated and managed properly in malnourished patients

3. Pseudohyponatremia can occur with hyperglycemia, hyperlipidemia, or hyperproteinemia and requires appropriate correction

4. Transcellular shifts of electrolytes can cause acute changes without actual total body deficit or excess

5. Medication review is essential as many common medications can cause or worsen electrolyte disorders

6. Multiple concurrent electrolyte abnormalities are common and may require prioritized correction (e.g., correct hypomagnesemia before hypokalemia)