Hypocalcaemia

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 ionized 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: Corrected calcium (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level in g/dL; in SI units: Corrected calcium (mmol/L) = measured total Ca (mmol/L) + 0.02 (40 - serum albumin [g/L]), where 40 represents the average albumin level in g/L. 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 hormone [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.


 * Eating disorders
 * Exposure to mercury, including infantile acrodynia
 * Excessive dietary magnesium, as with supplementation.
 * Prolonged use of medications/laxatives containing magnesium
 * Chelation Therapy for metal exposure, particularly EDTA
 * Absent parathyroid hormone (PTH)
 * Hereditary hypoparathyroidism
 * Acquired hypoparathyroidism
 * Hypomagnesaemia
 * Following parathyroidectomy, "Hungry Bone Syndrome"
 * Following thyroidectomy, the parathyroid glands are located very close to the thyroid and are easily injured or even accidentally removed during thyroidectomy
 * In DiGeorge Syndrome, 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.
 * Ineffective PTH
 * Chronic renal failure
 * Absent active vitamin D
 * Decreased dietary intake
 * Decreased sun exposure
 * Defective Vitamin D metabolism
 * Anticonvulsant therapy
 * Vitamin-D dependent rickets, type I
 * Ineffective active vitamin D
 * Intestinal malabsorption
 * Vitamin-D dependent rickets, type II
 * Pseudohypoparathyroidism
 * Deficient PTH
 * Severe acute hyperphosphataemia
 * Tumour lysis syndrome
 * Acute renal failure
 * Rhabdomyolysis (initial stage)
 * Exposure to hydrofluoric acid
 * As a complication of pancreatitis
 * As a result of hyperventilation
 * Alkalosis, often caused by hyperventilation
 * Neonatal hypocalcaemia
 * Very low birth weight (less than 1500 grams)
 * Gestational age less than 32 weeks

Symptoms
Can be recalled by the mnemonic "CATS go numb" (or, perhaps, CATPee!)- Convulsions, Arrythmias, Tetany and numbness/parasthesias in hands, feet, around mouth and lips.
 * Petechiae 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 (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 tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)
 * Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)
 * Tendon reflexes are hyperactive
 * Life threatening complications
 * Laryngospasm
 * Cardiac arrhythmias
 * 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 ampoules of intravenous calcium gluconate 10% is given slowly in a period of 10 minutes, 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.
 * 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.

Animals
Farm animals, mainly cows, can suffer hypocalcaemia, referred to as milk fever, 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.

Alkalosis
As blood plasma 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.