Calcium, Ionized

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Subject: Calcium, Ionized

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Definition

  • Ionized calcium is the physiologically active form of calcium. Ionized calcium homeostasis is regulated by the parathyroid glands, bone, kidney, and intestine. It is most frequently used in ICUs and operating rooms.

  • Normal range: 4.6–5.3 mg/dL.

  • Critical range: <4.1 or >5.9 mg/dL.

Use

  • In patients with hypocalcemia or hypercalcemia with borderline serum calcium and altered serum proteins.

  • Approximately 50% of calcium is ionized; 40–45% is bound to albumin; 5–10% is bound to other anions (e.g., sulfate, phosphate, lactate, and citrate); only the ionized fraction is physiologically active. Total calcium values may be deceiving, because they may be unchanged even if ionized calcium values are changed (e.g., increased blood pH increases protein-bound calcium and decreases ionized calcium, and PTH has the opposite effect) (blood pH should always be performed with ionized calcium, which is increased in acidosis and decreased in alkalosis). However, in critically ill patients, elevated total serum calcium usually indicates ionized hypercalcemia, and normal total serum calcium is evidence against ionized hypocalcemia.

  • Ionized calcium is the preferred measurement rather than total calcium, because it is physiologically active and can be rapidly measured, which may be essential in certain situations (e.g., liver transplantation and rapid or large transfusion of citrated blood make interpretation of total calcium nearly impossible).

  • Life-threatening complications are frequent when serum ionized calcium <2 mg/dL.

  • With multiple blood transfusions, ionized calcium <3 mg/dL may be an indication to administer calcium.

Interpretation

Increased In

  • Normal total serum calcium associated with hypoalbuminemia may indicate ionized hypercalcemia.

  • About 25% of patients with hyperparathyroidism have normal total but increased ionized calcium levels.

  • Acidosis

  • Metastatic bone tumor

  • Milk-alkali syndrome

  • Multiple myeloma

  • Paget disease

  • Sarcoidosis

  • Tumors producing a PTH-like substance

  • Vitamin D intoxication

Decreased In

  • Alkalosis (e.g., hyperventilation, to control increased intracranial pressure) (total serum calcium may be normal), administration of bicarbonate to control metabolic acidosis

  • Increased serum free fatty acids (increased calcium binding to albumin) due to

  • Hypoparathyroidism (primary, secondary)

  • Vitamin D deficiency

  • Toxic shock syndrome

  • Fat embolism

  • Hypokalemia protects the patient from hypocalcemic tetany; correction of hypokalemia without correction of hypocalcemia may provoke tetany

  • Malabsorption

  • Osteomalacia

  • Pancreatitis

  • Renal failure

  • Rickets

Limitations

  • Differences in specimen preparation and electrode selectivity are probably responsible for differences in reported reference ranges. Heparin itself causes 0.04 mg/dL decrease for each unit added per milliliter of blood.

  • Adjusting the pH of the specimen to 7.4 at the time of measurement is not necessary if the specimen is collected anaerobically.

  • Various formulas are available for calculating ionized calcium using total calcium, albumin, and total protein. However, these formulas may not apply in some situations; their use is discouraged.

  • Hypomagnesemia or hypermagnesemia; patients respond to serum magnesium that becomes normal but not to calcium therapy. Serum magnesium should always be measured in any patient with hypocalcemia.

  • Increase of ions to which calcium is bound:

    • Phosphate (e.g., phosphorus administration in treatment of DKA, chemotherapy causing tumor lysis syndrome, rhabdomyolysis)

    • Bicarbonate

    • Citrate (e.g., during blood transfusion)

    • Radiographic contrast media containing calcium chelators

 
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