Hypocalcemia
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Hypocalcemia is a medical condition characterized by low
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...
levels in the
blood serum Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not ...
. The normal range of blood calcium is typically between 2.1–2.6  mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol/L are defined as hypocalcemic. Mildly low levels that develop slowly often have no symptoms. Otherwise symptoms may include numbness, muscle spasms,
seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...
, confusion, or
cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possi ...
. The most common cause for hypocalcemia is
iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 27 ...
hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...
. Other causes include other forms of hypoparathyroidism, vitamin D deficiency,
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
,
pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic p ...
, calcium channel blocker overdose,
rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of ...
,
tumor lysis syndrome Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off ( lysed) from the treatment, releasing their contents into the blo ...
, and medications such as
bisphosphonates Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
or denosumab. Diagnosis should generally be confirmed with a
corrected calcium Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...
or
ionized calcium Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...
level. Specific changes may be seen on an electrocardiogram (ECG). Initial treatment for severe disease is with intravenous
calcium chloride Calcium chloride is an inorganic compound, a salt with the chemical formula . It is a white crystalline solid at room temperature, and it is highly soluble in water. It can be created by neutralising hydrochloric acid with calcium hydroxide. Ca ...
and possibly
magnesium sulfate Magnesium sulfate or magnesium sulphate (in English-speaking countries other than the US) is a chemical compound, a salt with the formula , consisting of magnesium cations (20.19% by mass) and sulfate anions . It is a white crystalline solid, ...
. Other treatments may include
vitamin D Vitamin D is a group of Lipophilicity, fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group ar ...
,
magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ...
, and calcium supplements. If due to
hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...
,
hydrochlorothiazide Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in ...
,
phosphate binders Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resultin ...
, and a
low salt diet A low sodium diet is a diet that includes no more than 1,500 to 2,400 mg of sodium per day. The human minimum requirement for sodium in the diet is about 500 mg per day, which is typically less than one-sixth as much as many diets "season ...
may also be recommended. About 18% of people who are being treated in hospital have hypocalcemia.


Signs and symptoms

The neuromuscular symptoms of hypocalcemia are caused by a positive
bathmotropic Bathmotropic often refers to modifying the degree of excitability specifically of the heart; in general, it refers to modification of the degree of excitability (threshold of excitation) of musculature in general, including the heart. It especiall ...
effect (i.e. increased responsiveness) due to the decreased interaction of calcium with
sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the chan ...
s. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, reduced calcium lowers the threshold for depolarization. The symptoms can be recalled by the mnemonic "CATs go numb" - convulsions, arrhythmias, tetany, and numbness in the hands and feet and around the mouth.


Causes

Hypoparathyroidism Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary m ...
is a common cause of hypocalcemia. 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. 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. Hypoparathyroidism may also be due to autoimmune problem. Some causes of hypocalcaemia are as follows:


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 Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Album ...
), bound to anions such as
phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phosph ...
and
citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in the ...
, and as free (unbound)
ionized calcium Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...
; all of these forms are ionised. Only the unbound calcium is physiologically active. Normal blood calcium level is between 8.5 and 10.5 mg/dL (2.12 to 2.62 mmol/L) and that of unbound calcium is 4.65 to 5.25 mg/dL (1.16 to 1.31 mmol/L).


Diagnosis

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 Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...
(mg/dL) = measured total Ca (mg/dL) + 0.8 * (4.0 - serum albumin /dL. Since calcium is also bound to small anions, it may be more useful to correct total calcium for both albumin and the anion gap.


Management

Management of this condition includes: *
Intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
calcium gluconate 10% can be administered, or if the hypocalcaemia is severe,
calcium chloride Calcium chloride is an inorganic compound, a salt with the chemical formula . It is a white crystalline solid at room temperature, and it is highly soluble in water. It can be created by neutralising hydrochloric acid with calcium hydroxide. Ca ...
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. * However, in either circumstance, maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)2-D3, i.e. calcitriol) are often necessary to prevent further decline


See also

*
Milk fever Milk fever, postparturient hypocalcemia, or parturient paresis is a disease, primarily in dairy cattle but also seen in beef cattle and non-bovine domesticated animals, characterized by reduced blood calcium levels ( hypocalcemia). It occurs foll ...
(hypocalcemia in animals) * Calcium deficiency (plant disorder) * Hypomagnesemia with secondary hypocalcemia


References


External links

{{Authority control Electrolyte disturbances Calcium Wikipedia medicine articles ready to translate Wikipedia neurology articles ready to translate Medical mnemonics