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Calcium, Ionized 

  • Author: Deborah Goldberg, MD; Chief Editor: Eric B Staros, MD  more...
 
Updated: Dec 05, 2014
 

Reference Range

Ionized calcium binds to negatively charged sites on protein molecules, competing with hydrogen ions for the same binding sites on albumin and other calcium-binding proteins. This binding is pH dependent and alters the level of ionized calcium in the blood. An increase in pH, alkalosis, promotes increased protein binding, which decreases free calcium levels. Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels.

The reference range of ionized calcium is 4.4-5.4 mg/dL (1.1-1.35 mmol/L)

Critical values are as follows:[1]

  • Less than 2 mg/dL (< 0.5 mmol/L) may produce tetany or life-threatening complications.
  • In patients with multiple blood transfusions, 2-3 mg/dL (< 0.5-0.75 mmol/L) may require calcium administration.
  • More than 7 mg/dL (>1.75 mmol/L) may cause coma.
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Interpretation

Ionized calcium is interpreted in conjunction with the total serum calcium measurement. An ionized calcium value within the reference range implies adequate calcium homeostasis, as this is a direct measure of calcium in its active form.

Normal ionized calcium level/high total calcium level

This condition is referred to as pseudohypercalcemia. It may result from the following:[2]

  • Hyperalbuminemia induced by extracellular volume depletion or by fluid movement out of the vascular space
  • Increased exogenous vitamin D intake

Normal ionized calcium level/low total calcium level

This condition is referred to as pseudohypocalcemia. It may result from hypoalbuminemia due to hepatic or renal disease.

Low ionized calcium level/normal total calcium level

This may result from the following:

Low ionized calcium level/high total calcium level

This may result from iatrogenic causes.

Low ionized calcium level/low total calcium level

This may result from the following:[2]

High ionized calcium level/normal total calcium level

This may result from the following:

High ionized calcium level/high total calcium level

This may result from the following:[2]

High ionized calcium level/low total calcium level

This may result from iatrogenic causes.

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Collection and Panels

Specifics for collection and panels are as follows:[3, 4]

  • Specimen type: Blood serum
  • Container: Vacutainer, red-black top or red top
  • Collection method: Venipuncture
  • Specimen volume: 5 mL
  • Panels: Serum electrolytes, basic metabolic panel, complete metabolic panel
  • Other instructions: Patients must fast for 6 hours before the blood sample is drawn
  • Measurement of ionized calcium is by ion-selective electrodes.

Related tests are as follows:[2]

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Background

Description

Calcium is the fifth most abundant element and is the most prevalent cation in the human body. Approximately 1-1.3 kg of calcium can be found in a healthy adult, 99% of which is in the form of hydroxyapatite in the skeleton; the remaining 1% is contained in the extracellular fluid (ECF).

Serum (plasma) calcium exists in 3 distinct forms. Approximately 15% is complexed calcium bound to organic and inorganic anions, 40% is bound to albumin, and the remaining 45% circulates as free ionized calcium.

Calcium is essential for bone mineralization, neuromuscular function, and secretion of hormones and enzymes. Because calcium is not made in the body, a diet that contains calcium is essential to maintain normal serum calcium levels. Calcium-rich foods include yogurt, cheese, eggs, milk, spinach, fish, okra, broccoli, almonds, sesame seeds, and peas. Calcitriol, the most active metabolite of vitamin D in calcium homeostasis, increases serum calcium levels by promoting calcium absorption in the intestines and kidney. It also promotes calcium mobilization from bone via resorption.[1]

The plasma concentration of calcium depends directly on the net balance of bone mineral deposition and resorption, intestinal absorption, and renal excretion. The hormones responsible for regulating these processes include PTH, calcitonin, and 1,25-dihydroxyvitamin D.

Ionized calcium binds to negatively charged sites on protein molecules, competing with hydrogen ions for the same binding sites on albumin and other calcium-binding proteins. This binding is pH dependent and alters the level of ionized calcium in the blood. An increase in pH, alkalosis, promotes increased protein binding, which decreases free calcium levels. Acidosis, on the other hand, decreases protein binding, resulting in increased free calcium levels.

Calcium is removed from the body in the form of skin, nails, hair, sweat, urine, and feces.

Indications/Applications

Assessing the total calcium level is part of a routine health screening, included in the comprehensive metabolic panel and basic metabolic panel, and is used to measure both ionized calcium and bound calcium.[1]

Measurement of the total calcium alone may sometimes be misleading, since this measurement can change without alteration in the ionized calcium concentration. In hypoalbuminemia, although ionized calcium levels remain normal, total calcium levels decrease. The equation used to measure corrected calcium in cases of hyperalbuminemia/hypoalbuminemia is as follows:[2]

Corrected (Ca) = Measured total (Ca) + (0.8 x [4.5 - (alb)])

Additionally, in patients who have chronic kidney disease and low serum bicarbonate levels, a low serum albumin level, or both, it is preferable to measure the ionized free calcium rather than the total calcium in order to diagnose hypocalcemia or hypercalcemia.[5]

Indications for testing of ionized calcium are as follows:

  • Neonatal hypocalcemia due to immature parathyroid gland, resulting in a lack of hypocalcemia symptoms
  • Critically illness
  • Chronic liver disease
  • Chronic kidney disease
  • Abnormal total serum calcium levels
  • Hyperparathyroidism/hypoparathyroidism
  • Numbness around the mouth and in the hands and feet
  • Muscle spasms around the mouth and in the hands and feet

Considerations

Drugs that increase ionized calcium levels include the following:[2]

  • Calcium salts
  • Hydralazine
  • Lithium
  • Thiazide diuretics
  • Thyroxine

Drugs that decrease ionized calcium levels include the following:[1]

  • Heparin
  • Citrate
  • Intravenous lipids
  • Epinephrine
  • Norepinephrine
  • Isoproterenol
  • Alcohol
  • Ethylenediaminetetraacetic acid
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Contributor Information and Disclosures
Author

Deborah Goldberg, MD Resident Physician, Departments of Internal Medicine and Pediatrics, St Louis University Hospital and Cardinal Glennon Children’s Hospital

Deborah Goldberg, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

References
  1. Delmar's Guide to Laboratory and Diagnostic Tests. 2nd Edition. 2010.

  2. Jacques Wallach. Interpretation of Diagnostic Tests. 8th Edition. Lippincott Williams & Wilkins;

  3. McPherson RA, Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods: Expert Consult - Online and Print. 22nd ed. Saunders; 2011.

  4. Jafri L, Khan AH, Azeem S. Ionized calcium measurement in serum and plasma by ion selective electrodes: comparison of measured and calculated parameters. Indian J Clin Biochem. 2014 Jul. 29(3):327-32. [Medline]. [Full Text].

  5. Tartaglia F, Giuliani A, Sgueglia M, Patrizi G, Di Rocco G, Blasi S, et al. Is ionized calcium a reliable predictor of hypocalcemia after total thyroidectomy? A before and after study. G Chir. 2014 Jan-Feb. 35(1-2):27-35. [Medline].

  6. Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007. chap 28.

  7. George L. Ackerman. Chapter 194. Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990.

  8. Wysolmerski JJ, Insogna KL. The parathyroid glands, hypercalcemia, and hypocalcemia. Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007. chap 266.

 
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