Electrolyte Disorders: Calcium, Phosphorus, Magnesium

Electrolyte Disorders: Calcium, Phosphorus, and Magnesium

• Learning Objectives:
  • Describe the physiological role of calcium, phosphorus, and magnesium in the human body
  • Identify common causes of calcium, phosphorus, and magnesium disorders
  • Recognize these disorders based on clinical presentation
  • Explain the mechanisms of action of therapies used to treat hypercalcemia and hyperphosphatemia
  • Design a patient care plan and treatment regimen for calcium, phosphorus, and magnesium disorders
• Electrolyte Abnormalities: Treatment Indications and Goals
  • Indications: Dependent on severity (how far the electrolyte level is from normal) and the speed of development (acute vs. chronic)
    • Acute: ≤ 48 hours
    • Chronic: > 48 hours
  • Goals:
    • Reverse signs and symptoms
    • Identify and correct/manage the underlying cause
    • Restore electrolytes to normal values

Calcium

• Calcium Homeostasis: Disorders related to calcium content in extracellular fluid (ECF)
  • Ionized Calcium: The physiologically active form of calcium. ~50% of calcium in ECF is bound to protein, primarily albumin.
• Corrected Calcium: -Formula: Measured Calcium + (0.8 x [4 g/dL - Measured Albumin])

Hypercalcemia

• Definition: Serum calcium > 10.5 mg/dL (2.63 mmol/L) or ionized calcium > 5.6 mg/dL
• Severity Scale: Categorized based on total and ionized calcium levels
  • Mild: 10.5-11.9 mg/dL (5.6-8 mg/dL ionized)
  • Moderate: 12-13.9 mg/dL (8-10 mg/dL ionized)
  • Severe: 14-16 mg/dL (10-12 mg/dL ionized)

Hypercalcemia: Treatment Algorithm

• Symptomatic (Ca > 12 mg/dL):

  • eGFR > 30: IV saline rehydration, loop diuretics, calcitonin
  • **eGFR < 30 or HF with EF <25%: ** Calcitonin, Bisphosphonates, Denosumab, Corticosteroids - treat underlying malignancy when suspected

• Asymptomatic (Ca < 12 mg/dL): Observe, Correct volume depletion, stop offending medications

IV Saline Rehydration

• Mechanism: Volume expansion with normal saline (NS) to increase natriuresis (sodium excretion) and urinary calcium excretion
• Treatment: Bolus of 1-2 L of NS, followed by maintenance infusion of 250-300 mL/hr
• Duration: Until fluid resuscitation is complete and serum calcium approaches the upper limit of normal, or response is seen in 24-48 hrs.
• Place in Therapy: First-line for symptomatic hypercalcemia (serum calcium >12 mg/dL)

Loop Diuretics

• Mechanism: Block calcium and sodium reabsorption in the loop of Henle, augmenting the calciuric effect of saline.
• Use: In combination with IV isotonic fluids (NEVER as monotherapy) for patients who have normal to moderately impaired kidney function and serum calcium is >12 mg/dL or symptomatic; to minimize volume overload from high doses of IV fluids.
• Dosing: Monitor IV every 1-4 hours of furosemide or equivalent loop diuretic dose.

Calcitonin

• Mechanism: Inhibits osteoclast activity, reduces renal tubular reabsorption of calcium (and thus promotes calciuresis).
• Use: First-line in cases with contraindications to IV saline rehydration (e.g., heart failure with EF < 25% or eGFR<30) or for symptomatic or moderate-severe hypercalcemia (Ca > 12 mg/dL.
• Dosage: 4 units/kg SQ or IM every 12 hours

Bisphosphonates (IV)

• Mechanism: Block bone resorption and inhibit osteoclasts, lowering blood calcium levels.
• Use: First-line for long-term, chronic treatment of moderate-severe hypercalcemia of malignancy
• When to use: In severe cases or when other therapies aren't working, specifically when hypercalcemia of malignancy is suspected.
• Common types and dosages:
  • Pamidronate: 30-90 mg IV over 2-24 hours
  • Zoledronic Acid: 4-8 mg IV over 15 minutes (Do not give if CrCL <30)

Denosumab

• Mechanism: Monoclonal antibody that inhibits RANKL, preventing osteoclast formation.
• Use: Chronic treatment in patients with hypercalcemia of malignancy when IV bisphosphonate therapy has failed or is not an option due to severe renal dysfunction (serum calcium >12.5 mg/dL after >7 days of therapy).
• Adverse Effects: Osteonecrosis of the jaw, severe symptomatic hypocalcemia (CKD patients).

Corticosteroids

• Mechanism: Reduce gastrointestinal calcium absorption by inhibiting vitamin D activation
• Use: In hypercalcemia associated with malignancies that overproduce calcitriol (multiple myeloma, leukemia, lymphoma).
• Dosage Prednisone 40-60mg PO or equivalent, for 3-5 days, followed by maintenance dose of 10-30 mg/day

Hypocalcemia

• Definition: Serum calcium < 8.5 mg/dL (2.1 mmol/L) or ionized calcium < 4.4 mg/dL (1.1 mmol/L)

Hypocalcemia: Treatment Algorithm

• Symptomatic (acute): IV calcium chloride or gluconate over 10 minutes; IV bolus or initial 1 g/hr infusion
• Asymptomatic (acute): IV calcium gluconate bolus (1 g/hr)
• Asymptomatic (chronic): Oral calcium supplementation (1-3 g/day) or vitamin D, especially when serum 25(OH) vitamin D levels are very low.

Hypophosphatemia

• Definition: Serum phosphorus <2.5 mg/dL
• Severity Scale: Categorized based on serum phosphorus.
  • Mild: 2-2.4mg/dL
  • Moderate: 1-2 mg/dL
  • Severe: <1 mg/dL

Hypophosphatemia: Treatment

• Mild-Moderate (1-2 mg/dL): Oral phosphate salts (1.5-2 g/day), divided doses.
• Severe (<1 mg/dL): IV phosphate repletion (sodium or potassium phosphate 15-30 mmol/ in 250 mL of D5W or NS over 3 hours).

Phosphorus Replacement Therapy

• Oral Therapy: Various products offering different amounts of phosphorus, tailored to serum potassium (K) levels.
• IV Therapy: IV administration when oral isn't feasible or when severe symptoms are present.

Magnesium

• Magnesium distribution: Predominantly in bone (67%) and muscle (20%)
• Normal Magnesium levels: 1.7-2.4 mg/dL (1.4-1.8 mEq/L)

Hypermagnesemia

• Definition: Serum Magnesium >2.4 mg/dL (2 mEq/L)

Hypermagnesemia: Treatment

• Reduce Magnesium intake
• IV Elemental Calcium - 100-200 mg (Calcium Gluconate 1-2g IV)
• Enhance Magnesium elimination
  • Normal renal function (CKD 1-3): Furosemide (40mg IV) or equivalent diuretic + isotonic fluids
  • ESRD (CKD 4-5 or end stage renal disease): Dialysis

Hypomagnesemia

• Definition: Serum Magnesium < 1.7 mg/dL (1.4 mEq/L)

Hypomagnesemia: Treatment

• Mild-Moderate (1.2-1.7 mg/dL): PO magnesium supplementation (400-800 mg/day magnesium oxide).
• Severe (≤ 1.2 mg/dL) or symptomatic: IV magnesium sulfate (8-12 g over 24 hrs divided doses) or (4-6 g divided doses over 3-5 days).

Common Calcium, Phosphorus, and Magnesium Salts

• Tables provided in the slides summarize different products and their elemental contents.

Take Home Points

• Electrolyte treatment depends on the severity and underlying cause.
• "Hyper-" electrolyte treatment aims to eliminate or redistribute.
• "Hypo-" electrolyte treatment often involves supplementation, IV or PO route depending on the acuity and severity.