Evaluation of hypocalcemia

Hypocalcemia is a state of electrolyte imbalance in which the circulating serum calcium level is low. During hypocalcemia, the total calcium level and the ionized calcium level fall below the laboratory reference range.[1]Hannan FM, Thakker RV. Investigating hypocalcaemia. BMJ. 2013 May 9;346:f2213.

Hypocalcemia may occur subsequent to failure of any of the mechanisms by which serum calcium concentration is maintained. But it is usually the result of failure of parathyroid hormone secretion, vitamin D deficiency, or an inability to release calcium from bone.

The clinical features of hypocalcemia largely manifest through neuromuscular excitability.[2]Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335 http://www.ncbi.nlm.nih.gov/pubmed/18535072?tool=bestpractice.com ​ Hypocalaemia can present acutely and be life threatening; early recognition and correction is critical.[3]Turner J, Gittoes N, Selby P, et al. Society for endocrinology endocrine emergency guidance: emergency management of acute hypocalcaemia in adult patients. Endocr Connect. 2016 Sep;5(5):G7-8. https://ec.bioscientifica.com/view/journals/ec/5/5/G7.xml http://www.ncbi.nlm.nih.gov/pubmed/27935815?tool=bestpractice.com ​ Quantitatively severe hypocalcemia can sometimes present with few symptoms, if onset has been protracted and chronic.[2]Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335 http://www.ncbi.nlm.nih.gov/pubmed/18535072?tool=bestpractice.com [4]Pepe J, Colangelo L, Biamonte F, et al. Diagnosis and management of hypocalcemia. Endocrine. 2020 Sep;69(3):485-95. http://www.ncbi.nlm.nih.gov/pubmed/32367335?tool=bestpractice.com ​ 

Pathophysiology

Calcium is one of the most abundant electrolytes in the body, and is essential for cell function, cell membrane stability, neuronal transmission, bone physiology, blood homeostasis, and cell signaling.[5]Anderson T, Bowie R, van Niekerk A. Calcium disorders. Prim Care. 2024 Sep;51(3):391-403. http://www.ncbi.nlm.nih.gov/pubmed/39067966?tool=bestpractice.com [6]Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010 Jan;5 Suppl 1:S23-30. https://journals.lww.com/cjasn/fulltext/2010/01001/calcium_metabolism_in_health_and_disease.4.aspx http://www.ncbi.nlm.nih.gov/pubmed/20089499?tool=bestpractice.com ​​​​ 

Approximately 40% of circulating calcium is bound to proteins (mostly albumin), 13% is bound to anions (such as sulfates, phosphates, lactate, citrate, and bicarbonate), and the remaining 47% circulates as biologically active calcium in an ionized form.[7]Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Crit Care Resusc. 2002 Dec;4(4):301-6. https://www.sciencedirect.com/science/article/pii/S1441277223011936 http://www.ncbi.nlm.nih.gov/pubmed/16573443?tool=bestpractice.com

Calcium levels are tightly controlled by parathyroid hormone and vitamin D. When serum calcium levels decrease, secretion of parathyroid hormone increases. As a result, there is increased reabsorption of calcium in the kidneys, bone resorption, and vitamin D secretion. Vitamin D causes increased calcium absorption in the gastrointestinal tract.[2]Cooper MS, Gittoes NJ. Diagnosis and management of hypocalcaemia. BMJ. 2008 Jun 7;336(7656):1298-302. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2413335 http://www.ncbi.nlm.nih.gov/pubmed/18535072?tool=bestpractice.com [6]Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010 Jan;5 Suppl 1:S23-30. https://journals.lww.com/cjasn/fulltext/2010/01001/calcium_metabolism_in_health_and_disease.4.aspx http://www.ncbi.nlm.nih.gov/pubmed/20089499?tool=bestpractice.com

Circulating calcium levels are impaired by several factors, but hypocalcemia is mainly secondary to the imbalance of calcium absorption, excretion, and distribution.[6]Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010 Jan;5 Suppl 1:S23-30. https://journals.lww.com/cjasn/fulltext/2010/01001/calcium_metabolism_in_health_and_disease.4.aspx http://www.ncbi.nlm.nih.gov/pubmed/20089499?tool=bestpractice.com ​