Calcium circulates bound to proteins, complexed with anions, or as unbound, ionized calcium. Ionized calcium is the physiologically active form of calcium, and may provide more useful information than total serum calcium when there are acid-base disorders or abnormalities of serum protein.


The ionized calcium can be estimated from total serum calcium and total protein levels. While the estimates are relatively accurate when calcium levels are normal, they are of little value in patients with hypercalcemia or hypocalcemia.


Patient Preparation: The patient should be lying down for at least 30 minutes prior to sample collection.


Specimens: Serum, heparinized whole blood or heparinized plasma may be used. The specimen should be collected anaerobically. The specimen should be placed on ice and sent to the laboratory for immediate testing.


Testing: Testing is typically done with an ion specific electrode.




ionized calcium (Zeisler) =

= ((6.25 * (total calcium)) - ((total protein) * 3/8)) / ((total protein) + 6.5)


ionized calcium (Zeisler, simplified) =

= ((6 * (total calcium)) - ((total protein) / 3)) / ((total protein) + 6)


ionized calcium (McClean and Hastings) =

= 0.5 * (((total calcium) - (total protein) - K) + (( (4K * (total calcium)) +

(((total protein) - (total calcium) + K) ^2))^0.5))


where for the McClean and Hastings equation:

• (total calcium) = (ionized calcium) + (protein bound calcium) = (ionized calcium) + (((ionized calcium) * (total protein)) / ((ionized calcium) + K))

• this equation when reworked becomes a quadratic equation, giving the equation of McClean and Hastings

• K = 10^(-2.22) = 0.006



• ionized calcium varies with age and sample; in adult serum it ranges from 4.64-5.28 mg/dL (1.16-1.32 mmol/L)

• elevated in: vitamin D ingestion, malignancies, PTH-producing neoplasms, and primary hyperparathyroidism

• decreased in: vitamin D deficiency, hypoparathyroidism, pseudohypoparathyroidism, magnesium deficiency, alkalosis, pancreatitis, trauma, burns, septicemia and many other conditions.


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