Hypocalcaemia
Encyclopedia
In medicine
, hypocalcaemia (or hypocalcemia) is the presence of low serum
calcium
levels in the blood
, usually taken as less than 2.1 mmol/L or 9 mg/dl or an ion
ized calcium level of less than 1.1 mmol/L or 4.5 mg/dL. It is a type of electrolyte disturbance
. In the blood, about half of all calcium is bound to proteins such as serum albumin
, but it is the unbound, or ionized, calcium that the body regulates. If a person has abnormal levels of blood proteins, then the plasma calcium may be inaccurate. The ionized calcium level is considered more clinically accurate in this case. In the setting of low serum albumin (frequently seen in patients with chronic diseases, hepatic disease or even long term hospitalization), the formula for corrected calcium is: CorrCa = Measured serum Ca + [(4.0 − measured serum albumin) * 0.8]. Thus, if the albumin is low, the measured calcium may appear low when in fact it is physiologically within normal limits.
[PTH] deficiency/malfunction, a Vitamin D
deficiency, or unusually high magnesium levels hypermagnesaemia, or low magnesium levels hypomagnesaemia.
More specifically, hypocalcaemia may be associated with low PTH levels as seen in hereditary hypoparathyroidism, acquired hypoparathyroidism (surgical removal MCC of hypoparathyroidism), and hypomagnesaemia. Hypocalcaemia may be associated with high PTH levels when the parathyroid hormone is ineffective; in chronic renal failure, the hydroxylation of vitamin D is ineffective, calcium levels in the blood fall, and high PTH levels are produced in response to the low calcium, but fail to return calcium levels to normal.
, after calving
. This is due to a large calcium demand and a slow response from the animal in terms of intestinal absorption or bone resorption. The condition is also linked to low milk production. If a cow or other animal is affected it will collapse and have muscle spasms. It will eventually enter a coma and can die.
The treatment is an injection of calcium gluconate. It can be prevented in part by avoiding excess calcium, or more commonly, by regulating potassium
in the diet before calving.
hydrogen ion concentration decreases, caused by respiratory or metabolic alkalosis
, freely ionized calcium concentration decreases. This freely ionized calcium is the biologically active component of blood calcium. Since a portion of both hydrogen ions and calcium are bound to serum albumin
, when blood becomes alkalotic, bound hydrogen ions dissociate from albumin, freeing up the albumin to bind with more calcium and thereby decreasing the freely ionized portion of total serum calcium. For every 0.1 increase in pH, ionized calcium decreases by about 0.05 mmol/L. This hypocalcaemia related to alkalosis is partially responsible for the cerebral vasoconstriction
that causes the lightheadedness
, fainting, and paraesthesia often seen with hyperventilation
.
Tetany may also be seen with this condition.
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, hypocalcaemia (or hypocalcemia) is the presence of low serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
levels in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, usually taken as less than 2.1 mmol/L or 9 mg/dl or an ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
ized calcium level of less than 1.1 mmol/L or 4.5 mg/dL. It is a type of electrolyte disturbance
Electrolyte disturbance
Electrolytes play a vital role in maintaining homeostasis within the body. They help to regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance and much more. Electrolyte imbalances can develop by the following mechanisms: excessive ingestion; diminished...
. In the blood, about half of all calcium is bound to proteins such as serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
, but it is the unbound, or ionized, calcium that the body regulates. If a person has abnormal levels of blood proteins, then the plasma calcium may be inaccurate. The ionized calcium level is considered more clinically accurate in this case. In the setting of low serum albumin (frequently seen in patients with chronic diseases, hepatic disease or even long term hospitalization), the formula for corrected calcium is: CorrCa = Measured serum Ca + [(4.0 − measured serum albumin) * 0.8]. Thus, if the albumin is low, the measured calcium may appear low when in fact it is physiologically within normal limits.
Cause
It manifests as a symptom of a parathyroid hormoneParathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
[PTH] deficiency/malfunction, a Vitamin D
Vitamin D
Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
deficiency, or unusually high magnesium levels hypermagnesaemia, or low magnesium levels hypomagnesaemia.
More specifically, hypocalcaemia may be associated with low PTH levels as seen in hereditary hypoparathyroidism, acquired hypoparathyroidism (surgical removal MCC of hypoparathyroidism), and hypomagnesaemia. Hypocalcaemia may be associated with high PTH levels when the parathyroid hormone is ineffective; in chronic renal failure, the hydroxylation of vitamin D is ineffective, calcium levels in the blood fall, and high PTH levels are produced in response to the low calcium, but fail to return calcium levels to normal.
- Eating disorders
- Exposure to mercury, including infantile acrodynia
- Excessive dietary magnesium, as with supplementation.
- Prolonged use of medications/laxatives containing magnesium
- Chelation TherapyChelation therapyChelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...
for metal exposure, particularly EDTAEDTAEthylenediaminetetraacetic acid, widely abbreviated as EDTA , is a polyamino carboxylic acid and a colourless, water-soluble solid. Its conjugate base is named ethylenediaminetetraacetate. It is widely used to dissolve limescale. Its usefulness arises because of its role as a hexadentate ligand... - Absent parathyroid hormoneParathyroid hormoneParathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...
(PTH)- Hereditary hypoparathyroidismHypoparathyroidismHypoparathyroidism is decreased function of the parathyroid glands with under production of parathyroid hormone. This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany , and several other symptoms...
- Acquired hypoparathyroidism
- Hypomagnesaemia
- Following parathyroidectomyParathyroidectomyAlso known as "Parathyroid gland removal", Parathyroidectomy is the surgical removal of one or more parathyroid glands. This procedure is used to remove primary tumors or hyperplasia of the glands, especially when they produce excessive parathyroid hormone. As drugs such as Fosamax do not treat the...
, "Hungry Bone Syndrome" - Following thyroidectomyThyroidectomyA thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. Surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland...
, the parathyroid glands are located very close to the thyroid and are easily injured or even accidentally removed during thyroidectomy - In DiGeorge SyndromeDiGeorge syndrome22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a...
, a disease characterized by the failure of the third and fourth pharyngeal pouches to develop, the parathyroid glands do not form and there is thus a lack of PTH.
- Hereditary hypoparathyroidism
- Ineffective PTH
- Chronic renal failureChronic renal failureChronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
- Absent active vitamin DVitamin DVitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
- Decreased dietary intake
- Decreased sun exposure
- Defective Vitamin D metabolism
- AnticonvulsantAnticonvulsantThe anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
therapy - Vitamin-D dependent ricketsRicketsRickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
, type I
- Anticonvulsant
- Ineffective active vitamin D
- Intestinal malabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
- Vitamin-D dependent rickets, type II
- Intestinal malabsorption
- PseudohypoparathyroidismPseudohypoparathyroidismPseudohypoparathyroidism is a condition associated primarily with resistance to the parathyroid hormone. Patients have a low serum calcium and high phosphate, but the parathyroid hormone level is actually appropriately high...
- Chronic renal failure
- Deficient PTH
- Severe acute hyperphosphataemia
- Tumour lysis syndrome
- Acute renal failureAcute renal failureAcute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
- RhabdomyolysisRhabdomyolysisRhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
(initial stage)
- Severe acute hyperphosphataemia
- Exposure to hydrofluoric acidHydrofluoric acidHydrofluoric acid is a solution of hydrogen fluoride in water. It is a valued source of fluorine and is the precursor to numerous pharmaceuticals such as fluoxetine and diverse materials such as PTFE ....
- As a complication of pancreatitisPancreatitisPancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
- As a result of hyperventilation
- AlkalosisAlkalosisAlkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
, often caused by hyperventilation - Chelation TherapyChelation therapyChelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...
- Neonatal hypocalcaemia
- Very low birth weight (less than 1500 grams)
- Gestational age less than 32 weeks
Symptoms
- PetechiaPetechiaA petechia is a small red or purple spot on the body, caused by a minor hemorrhage ."Petechiae" refers to one of the three major classes of purpuric skin conditions. Purpuric eruptions are classified by size into three broad categories...
which appear as on-off spots, then later become confluent, and appear as purpura (larger bruised areas, usually in dependent regions of the body). - Oral, perioral and acral paresthesias, tingling or 'pins and needles' sensation in and around the mouth and lips, and in the extremities of the hands and feet. This is often the earliest symptom of hypocalcaemia.
- Carpopedal and generalized tetany (medical sign), (unrelieved and strong contractions of the hands, and in the large muscles of the rest of the body) are seen.
- Latent tetany
- Trousseau sign of latent tetanyTrousseau sign of latent tetanyTrousseau sign of latent tetany is a medical sign observed in patients with low calcium. This sign may become positive before other gross manifestations of hypocalcemia such as hyperreflexia and tetany, but is generally believed to be more sensitive than the Chvostek sign for hypocalcemia.To...
(eliciting carpal spasm by inflating the blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
cuff and maintaining the cuff pressure above systolicSystole (medicine)Systole is the contraction of the heart. Used alone, it usually means the contraction of the left ventricle.In all mammals, the heart has 4 chambers. The left and right ventricles pump together. The atria and ventricles pump in sequence...
) - Chvostek's sign (tapping of the inferior portion of the zygomaZygomaThe term zygoma generally refers to the zygomatic bone, a bone of the human skull commonly referred to as the cheekbone or malar bone, but it may also refer to:...
will produce facial spasms)
- Trousseau sign of latent tetany
- Tendon reflexes are hyperactive
- Life threatening complications
- LaryngospasmLaryngospasmIn medicine, laryngospasm is an uncontrolled/involuntary muscular contraction of the laryngeal cords. The condition typically lasts less than 60 seconds, and causes a partial blocking of breathing in, while breathing out remains easier. It may be triggered when the vocal cords or the area of the...
- Cardiac arrhythmias
- Laryngospasm
- ECG changes include:
- Intermittent QT prolongation, or intermittent prolongation of the QTc (corrected QT interval) on the EKG (electrocardiogram) is noted. The implications of intermittent QTc prolongation predisposes to life-threatening cardiac electrical instability (and this is therefore a more critical condition than constant QTc prolongation). This type of electrical instability puts the patient at high risk of torsades de pointes, a specific type of ventricular fibrillation which appears on an EKG (or ECG) as something which looks a bit like a sine wave with a regularly increasing and decreasing amplitude. (Torsades de pointes, as with any type of ventricular fibrillation, causes death, unless the patient can be electrically cardioverted, and returned to a normal cardiac rhythm.)
Management
- Two ampouleAmpouleAn ampoule is a small sealed vial which is used to contain and preserve a sample, usually a solid or liquid. Ampoules are commonly made of glass, although plastic ampoules do exist....
s of intravenous calcium gluconateCalcium gluconateCalcium gluconate is a mineral supplement.-Hypocalcemia:10% calcium gluconate solution is the form of calcium most widely used in the treatment of hypocalcemia. This form of calcium is superior to calcium lactate, but it only contains 0.93% calcium ion. Calcium gluconate is a salt of calcium and...
10% is given slowly in a period of 10 minutes, or if the hypocalcaemia is severe, calcium chlorideCalcium chlorideCalcium chloride, CaCl2, is a salt of calcium and chlorine. It behaves as a typical ionic halide, and is solid at room temperature. Common applications include brine for refrigeration plants, ice and dust control on roads, and desiccation...
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. calcitriolCalcitriolCalcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...
) are often necessary to prevent further decline.
Animals
Farm animals, mainly cows, can suffer hypocalcaemia, referred to as milk feverMilk fever
Milk fever, post-parturient hypocalcemia, or parturient paresis is a disease, usually of dairy cows, characterized by reduced blood calcium levels....
, after calving
Calving
Calving may refer to:*Calving, the process of giving birth to a calf*Ice calving, the process by which an iceberg breaks off from an ice shelf or glacier...
. This is due to a large calcium demand and a slow response from the animal in terms of intestinal absorption or bone resorption. The condition is also linked to low milk production. If a cow or other animal is affected it will collapse and have muscle spasms. It will eventually enter a coma and can die.
The treatment is an injection of calcium gluconate. It can be prevented in part by avoiding excess calcium, or more commonly, by regulating potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
in the diet before calving.
Alkalosis
As blood plasmaBlood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
hydrogen ion concentration decreases, caused by respiratory or metabolic alkalosis
Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
, freely ionized calcium concentration decreases. This freely ionized calcium is the biologically active component of blood calcium. Since a portion of both hydrogen ions and calcium are bound to serum albumin
Albumin
Albumin refers generally to any protein that is water soluble, which is moderately soluble in concentrated salt solutions, and experiences heat denaturation. They are commonly found in blood plasma, and are unique to other blood proteins in that they are not glycosylated...
, when blood becomes alkalotic, bound hydrogen ions dissociate from albumin, freeing up the albumin to bind with more calcium and thereby decreasing the freely ionized portion of total serum calcium. For every 0.1 increase in pH, ionized calcium decreases by about 0.05 mmol/L. This hypocalcaemia related to alkalosis is partially responsible for the cerebral vasoconstriction
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
that causes the lightheadedness
Lightheadedness
Light-headedness is a common and often unpleasant sensation of dizziness and/or feeling that one may be about to faint, which may be transient, recurrent, or occasionally chronic. In some cases, the individual may feel as though his or her head is weightless. The individual may also feel as...
, fainting, and paraesthesia often seen with hyperventilation
Hyperventilation
Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, causing excessive expulsion of circulating carbon dioxide. It can result from a psychological state such as a panic attack, from a physiological condition such as metabolic acidosis, can be brought about by...
.
Tetany may also be seen with this condition.
See also
- Calcium metabolismCalcium metabolismCalcium metabolism or calcium homeostasis is the mechanism by which the body maintains adequate calcium levels. Derangements of this mechanism lead to hypercalcemia or hypocalcemia, both of which can have important consequences for health....
- HypercalcaemiaHypercalcaemiaHypercalcaemia is an elevated calcium level in the blood. . It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists...
- Calcium deficiency (plant disorder)Calcium deficiency (plant disorder)Calcium deficiency is a plant disorder that can be caused by insufficient calcium in the growing medium, but is more frequently a product of low transpiration of the whole plant or more commonly the affected tissue. Plants are susceptible to such localized calcium deficiencies in low or non...
- Hypomagnesemia with secondary hypocalcemiaHypomagnesemia with secondary hypocalcemiaHypomagnesemia with secondary hypocalcemia is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone output by the...
- Electrolytes
External links
- Hypocalcemia Cleveland Clinic
- Endotext
- EKG abnormalities associated with hypocalcemia
- Seizures due to hypocalcaemia worsened by shifting towards alkalosis by bicarbonate therapy
- Hypocalcemia eMedicine overview
- Calcium Deficiency Calcium Deficiency Symptoms