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{{Short description|Low calcium levels in one's blood serum}}
{{For|the disorder of high blood calcium|Hypercalcemia}}
{{Infobox medical condition (new)
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| image = Polfa Warszawa Calcium Chloratum 67mg-per-ml 10ml - stack.jpg
| alt = Calcium chloride ampoules
| caption =
| field = [[Endocrinology]]
| symptoms = [[paresthesia|Numbness]], [[muscle spasms]], [[seizures]], confusion<ref name=EU2010/><ref name=Fong2012/>
| complications = [[Cardiac arrest]].<ref name=EU2010/><ref name=Fong2012/>
| onset =
| duration =
| types =
| causes = [[Hypoparathyroidism]], [[vitamin D deficiency]], [[kidney failure]], [[pancreatitis]], [[calcium channel blocker overdose]], [[rhabdomyolysis]], [[tumor lysis syndrome]], [[bisphosphonates]]<ref name=EU2010/><ref name=Fong2012/>
| risks =
| diagnosis = [[Blood serum]] < 2.1&nbsp;mmol/L ([[corrected calcium]] or [[ionized calcium]])<ref name=EU2010/><ref name=Fong2012/><ref name=Pat2006/>
| differential =
| prevention =
| treatment = [[Calcium supplements]], [[vitamin D]], [[magnesium sulfate]].<ref name=EU2010/><ref name=Fong2012/>
| medication =
| prognosis =
| frequency = ~18% of people in hospital<ref name=BMJ2008/>
| deaths =
}}
<!-- Definition and symptoms -->
'''Hypocalcemia''' is a medical condition characterized by low [[calcium]] levels in the [[blood serum]].<ref>{{cite book|last1=LeMone|first1=Priscilla|last2=Burke|first2=Karen|last3=Dwyer|first3=Trudy|last4=Levett-Jones|first4=Tracy|last5=Moxham|first5=Lorna|last6=Reid-Searl|first6=Kerry|title=Medical-Surgical Nursing|date=2015|publisher=Pearson Higher Education AU|isbn=9781486014408|page=237|url=https://books.google.com/books?id=MDXiBAAAQBAJ&pg=PA237|language=en|url-status=live|archive-url=https://web.archive.org/web/20161002044256/https://books.google.ca/books?id=MDXiBAAAQBAJ&pg=PA237|archive-date=2016-10-02}}</ref> The normal range of blood calcium is typically between 2.1–2.6&nbsp;[[mmol/L]] (8.8–10.7&nbsp;mg/dldL, 4.3–5.2 [[mEq/L]]), withwhile levels less than 2.1&nbsp;mmol/lL are defined as hypocalcemiahypocalcemic.<ref name=EU2010/><ref name=Pat2006>{{cite book|last1=Pathy|first1=M.S. John|title=Principles and practice of geriatric medicine|volume=2|date=2006|publisher=Wiley|location=Chichester [u.a.]|isbn=9780470090558|page=Appendix|edition=4.|doi=10.1002/047009057X.app01|chapter=Appendix 1: Conversion of SI Units to Standard Units}}</ref><ref name=BMJ2015>{{cite journal|last1=Minisola|first1=S|last2=Pepe|first2=J|last3=Piemonte|first3=S|last4=Cipriani|first4=C|title=The diagnosis and management of hypercalcaemia|journal=BMJ (Clinical Research Ed.)|date=2 June 2015|volume=350|pages=h2723|pmid=26037642|doi=10.1136/bmj.h2723|s2cid=28462200}}</ref> Mildly low levels that develop slowly often have no symptoms.<ref name="Fong2012">{{cite journal |last1=Fong |first1=J |last2=Khan |first2=A |date=February 2012 |title=Hypocalcemia: updates in diagnosis and management for primary care |journal=Canadian Family Physician |volume=58 |issue=2 |pages=158–62 |pmc=3279267 |pmid=22439169}}</ref><ref name=BMJ2008/> Otherwise symptoms may include [[paresthesia|numbness]], [[muscle spasms]], [[seizures]], confusion, or in extreme cases [[cardiac arrest]].<ref name=EU2010/><ref name=Fong2012/>
 
<!-- Cause and diagnosis -->
CommonThe causesmost includecommon cause for hypocalcemia is [[hypoparathyroidismiatrogenic]] and [[vitamin D deficiencyhypoparathyroidism]].<ref name="Fong2012" />{{cite journal|last1=Fong|first1=J|last2=Khan|first2=A|title=Hypocalcemia:Other updatescauses ininclude diagnosisother andforms managementof forhypoparathyroidism, primary[[vitamin care|journal=CanadianD Family Physician |date=February 2012|volume=58|issue=2|pages=158–62|pmid=22439169|pmc=3279267}}</ref> Others causes includedeficiency]], [[kidney failure]], [[pancreatitis]], [[calcium channel blocker overdose]], [[rhabdomyolysis]], [[tumor lysis syndrome]], and medications such as [[bisphosphonates]] or [[denosumab]].<ref name=EU2010/> Diagnosis should generally be confirmed withby adetermining the [[corrected calcium]] or [[ionized calcium]] level.<ref name=Fong2012/> Specific changes may also be seen on an [[electrocardiogram]] (ECG).<ref name=EU2010/>
 
<!-- Treatment and epidemiology -->
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==Causes==
[[Hypoparathyroidism]] is a common cause of hypocalcemia.<ref name="Nussey2013">{{Cite book|title = Endocrinology: An Integrated Approach|url = https://books.google.com/books?id=pjZvmnZpKXsC|publisher = CRC Press|date = 2013-04-08|page=194|isbn = 9780203450437|first1 = S. S.|last1 = Nussey|first2 = S. A.|last2 = Whitehead}}</ref> Calcium is tightly regulated by the [[parathyroid hormone]] (PTH). In response to low calcium levels, PTH levels rise, and conversely if there are high calcium levels then PTH secretion declines.<ref>{{Cite book|title = Understanding Medical Physiology: A Textbook for Medical Students|url = https://books.google.com/books?id=gUoRYgERRZMC|publisher = Jaypee Brothers Publishers|date = 2010-11-26|page = 465|isbn = 9789380704814|first1 = R. L.|last1 = Bijlani|first2 = S.|last2 = Manjunatha}}{{Dead link|date=January 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> However, in the setting of absent, decreased, or ineffective PTH hormone, the body loses this regulatory function, and hypocalcemia ensues. Hypoparathyroidism is commonly due to surgical destruction of the parathyroid glands.<ref name=Nussey2013/> Hypoparathyroidism may also be due to autoimmune problem.<ref>{{Cite web|title = Hypoparathyroidism. Parathyroid symptoms and disease {{!}} Patient|url = http://patient.info/doctor/hypoparathyroidism-pro|website = Patient|access-date = 2015-09-05}}</ref><ref>{{Cite web|url=https://rarediseases.org/rare-diseases/hypoparathyroidism/|title=Hypoparathyroidism|website=NORD (National Organization for Rare Disorders)|language=en-US|access-date=2019-01-09|quote=These cases may be called autoimmune hypoparathyroidism and develop when the body’sbody's own immune system mistakenly attacks parathyroid tissue and leads to the loss of the secretion of parathyroid hormone.}}</ref> Some causes of hypocalcaemia are as follows:{{citation needed|date=March 2020}}
 
{{Columns-list|colwidth=30em|
* [[Hyperphosphatemia]]<ref name=Metheny2012/>
* [[Vitamin D deficiency]]
* [[Cirrhosis|Chronic liver disease]]
* [[Edetate disodium]]<ref name="Metheny2012">{{cite book|last1=Metheny|first1=Norma|title=Fluid and electrolyte balance : nursing considerations|date=2012|publisher=Jones & Bartlett Learning|location=Sudbury, MA|isbn=978-0-7637-8164-4|page=93|edition=5th|url=https://books.google.com/books?id=6UNGDx4ifDcC&q=causes+of+hypocalcemia&pg=PA93|access-date=4 September 2015}}</ref>
* [[Magnesium deficiency]]<ref name="Helms2006">{{cite book|last1=Helms|first1=Richard|title=Textbook of therapeutics : drug and disease management|date=2006|publisher=Lippincott Williams & Wilkins|location=Philadelphia, Pa. [u.a.]|isbn=978-0-7817-5734-8|page=1035|edition=8.|url=https://books.google.com/books?id=aVmRWrknaWgC&q=causes+of+hypocalcemia&pg=PA1035|access-date=4 September 2015}}</ref>
* Prolonged use of medications/laxatives (magnesium)<ref name=Khan2012/>
* [[Osteomalacia]]<ref name=Helms2006/>
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* High level of [[lactic acid]] in the blood
* [[Pseudohypoparathyroidism]]
* [[Major trauma|Trauma]]<ref>{{cite journal|last1=Kronstedt|first1=Shane|last2=Roberts|first2=Nicholas|last3=Ditzel|first3=Ricky|last4=Elder|first4=Justin|last5=Steen|first5=Aimee|last6=Thompson|first6=Kelsey|last7=Anderson |first7=Justin|last8=Siegler|first8=Jeffrey|title=Hypocalcemia as a predictor of mortality and transfusion. A scoping review of hypocalcemia in trauma and hemostatic resuscitation.|journal=Transfusion|volume=62|issue=S1|pages=S158–S166|year=2022|doi=10.1111/trf.16965 |pmid=35748676|pmc=9545337}}</ref>
}}
 
==Mechanism==
 
Physiologically, blood calcium is tightly regulated within a narrow range for proper cellular processes. Calcium in the blood exists in three primary states: bound to proteins (mainly [[albumin]]), bound to anions such as [[phosphate]] and [[Citric acid|citrate]], and as free (unbound) [[ionized calcium]]; all of these forms are ionised. Only the unbound ionized calcium is physiologically active. Normal blood calcium level is between 8.5 toand 10.5&nbsp;mg/dL (2.12 to 2.62&nbsp;mmol/L) and that of unbound calcium is 4.65 to 5.25&nbsp;mg/dL (1.16 to 1.31&nbsp;mmol/L).<ref>{{Cite journal|last1=Siyam|first1=Fadi F.|last2=Klachko|first2=David M.|date=2013|title=What Is Hypercalcemia? The Importance of Fasting Samples|journal=Cardiorenal Medicine|volume=3|issue=4|pages=232–238|doi=10.1159/000355526|issn=1664-3828|pmc=3901605|pmid=24474951}}</ref>
 
==Diagnosis==
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Because a significant portion of calcium is bound to albumin, any alteration in the level of albumin will affect the measured level of calcium. A corrected calcium level based on the albumin level is: [[Corrected calcium]] (mg/dL) = measured total Ca (mg/dL) + 0.8 * (4.0 - serum albumin [g/dL]).<ref>{{cite book|title=Fluids & Electrolytes: A 2-in-1 Reference for Nurses|date=2006|publisher=Lippincott Williams & Wilkins|isbn=9781582554259|page=122|url=https://books.google.com/books?id=Ap2Gc5U0TPwC&pg=PA122|language=en|url-status=live|archive-url=https://web.archive.org/web/20170319113434/https://books.google.ca/books?id=Ap2Gc5U0TPwC&pg=PA122|archive-date=2017-03-19}}</ref>
Since calcium is also bound to small anions, it may be more useful to correct total calcium for both albumin and the [[anion gap]].<ref name =JALM2020>{{cite journal|last1=Yap|first1=E|last2=Roche-Recinos|first2=A|last3=Goldwasser|first3=P|title=Predicting Ionized Hypocalcemia in Critical Care: An Improved Method Based on the Anion Gap|journal= The Journal of Applied Laboratory Medicine|date=30 December 2019|volume=5|issue=1|pages=4–14|doi= 10.1373/jalm.2019.029314|pmid=32445343|doi-access=free}}</ref><ref name =CCA2022>{{cite journal|last1=Yap|first1=E|last2=Ouyang|first2=J|last3=Puri|first3=I|last4=Melaku|first4=Y|last5=Goldwasser|first5=P|title=Novel methods of predicting ionized calcium status from routine data in critical care: External validation in MIMIC-III|journal=Clinica Chimica Acta|date=1 June 2022|volume=531|pages=375–381|doi=10.1016/j.cca.2022.05.003|pmid=35526587|s2cid=248568849}}</ref>
 
==Management==
Management of this condition includes:{{citation needed|date=October 2017}}
* [[Intravenous]] [[calcium gluconate]] 10% can be administered, or if the hypocalcaemia is severe, [[calcium chloride]] is given instead. This is only appropriate if the hypocalcemia is acute and has occurred over a relatively short time frame. But if the hypocalcemia has been severe and chronic, then this regimen can be fatal, because there is a degree of acclimatization that occurs. The neuromuscular excitability, cardiac electrical instability, and associated symptoms are then not cured or relieved by prompt administration of corrective doses of calcium, but rather exacerbated. Such rapid administration of calcium would result in effective over correction – symptoms of hypercalcemia would follow.{{cn|date=April 2023}}
* However, in either circumstance, maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)<sub>2</sub>-D<sub>3</sub>, i.e. [[calcitriol]]) are often necessary to prevent further decline.{{cn|date=April 2023}}
 
==See also==