• Exists in two states
    • Free ionized form (approx. 50%)
    • Bound to other molecules (primarily albumin)
  • Ionized Ca2+ concentration is inversely proportional to pH

    Calcium Metabolism -

    Calcium Metabolism –

  • Ca2+ Metabolism
    • Vitamin D: aids in intestinal Ca2+ absorption
    • Parathyroid hormone (PTH)
      • Increases renal Ca2+ reabsorption
      • Arbitrates Vit D stimulated intestinal Ca2+ absorption
      • Mobilizes Ca2+ from bone
    •  Calcitonin
      • PTH antagonist
      • Inhibits renal Ca2+ reabsorption
      • Inhibits Ca2+ mobilization from bone
  • Ca2+ plays numerous critical roles including muscle contraction (skeletal and smooth), clotting factor activity and nerve conduction


  • Malignancy (multiple myeloma, metastases to bone)
  • Granulomatous disease (TB, sarcoidosis)
  • Endocrine (hyperthyroidism, hyperparathyroidism, adrenal insufficiency, pheochromocytoma)
  • Pharmacologic agents (thiazide diuretics, milk-alkali syndrome, PTH therapy for osteoporosis, lithium, Vitamin A)
  • Miscellaneous (Dehydration, rhabdomyolysis, prolonged immobilization, dietary, iatrogenic)

Clinical Manifestations

  • “Stones (renal), Bones (bone pain), Groans (abdominal pain) + Moans (Psychiatric overtones)”
  • Cardiac Effects
    • Bradydysrhythmias
    • AV block
    • Sinus Arrest
    • Atrial Fibrillation
    • Ventricular Tachycardia
    • QTc shortening
  • Neuropsychiatric Disorders
    • Major: AMS, seizures, weakness, lethargy, coma
    • Minor: Anxiety, depression, confusion, hallucinations
    • Hyporeflexia


  • Serum calcium > 10.5 mg/dL
    • 5 – 12.0 mg/dL considered moderate
    • > 14 mg/dL considered severe + potentially life-threatening
  • EKG
    • Short QTc interval (also caused by congenital short QT syndrome and digoxin)
    • Prolonged PR
    • Widened QRS complex
    • AV block


  • Supportive Care – ABCs, IV, O2, Monitor
  • Volume Expansion
    • The majority of patients with hypercalcemia have significant dehydration
    • Normal saline administration
      • Mechanism of action: Corrects volume depleted state and inhibits proximal tubule calcium resorption
      • Monitor other electrolytes (potassium, sodium)
      • Dose
        • Bolus to correct hypotension
        • Careful administration while monitoring overall fluid status (patients often have cardiac and/or renal dysfunction making them susceptible to volume overload)
        • Loop diuretics (i.e. furosemide)
          • Mechanism of action: Inhibits reabsorption of Na,K, Cl via the Na+-K+-2Cl cotransporter in the ascending loop of henle, thereby also inhibiting Ca2+ and Mg2+ reabsorption
          • Theoretical benefit of “forced diuresis” not proven in the literature
          • Should NOT be given until volume repletion completed as it can exacerbate hypercalcemia in this situation
        • Bisphosphonates
          • Mechanism of action: inhibit osteoclast-mediated bone resorption
          • Zoledronic acid
            • Preferred in hypercalcemia in the setting of malignancy
            • Dose: 4 mg IV over 15 minutes
          • Other Agents: Pamidronate, Etidronate
        • Calcitonin
          • Mechanism of action: inhibits Ca2+ absorption in the intestines, inhibits osteoclast activity, stimulates osteoblastic activity, inhibits renal tubular cell reabsorption
          • Dose: 4 IU/kg IM Q12
        • Cinacalcet
          • Mechanism of action: increases the sensitivity of Ca2+ receptors on parathyroid cells to reduce PTH levels and, thus Ca2+ levels
          • Indications: Hypercalcemia in patients with secondary hyperparathyroidism (i.e. CKD on dialysis, parathyroid carcinoma)
        • Other
          • Hemodialysis
          • Parathyroidectomy may be considered in patients with hypercalcemia caused by hyperparathyroidism

Take Home Points

  • Patients with severe hypercalcemia (> 14 mg/dL) are at risk for severe cardiac dysrhythmias and cardiac collapse
  • Treatment centers on volume repletion with normal saline with consideration for the addition of loop diuretics AFTER volume reexpansion is complete
  • As the patient begins to diurese, continually monitor electrolytes


Pfenning CL, Slovis CM: Electrolyte Disorders; in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2014, (Ch) 125: p 1636-53.

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