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

The neuromuscular symptoms of hypocalcemia are caused by a positive bathmotropic effect due to the decreased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, diminished calcium lowers the threshold for depolarization. The symptoms can be recalled by the mnemonic "CATS go numb"- Convulsions, Arrhythmias, 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 tachycardia, 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

Hypocalcaemia within a few days of parturition is of particular concern for dairy animals. A dairy cow might have about 3 g calcium circulating in the bloodstream, and with the onset of lactation, she may translocate more than 20 g of calcium to colostrum within a few hours, imposing sudden high demand for mobile calcium during a period when she may be eating very little. Hypocalcaemia may result within 48 to 72 hours after calving; in such circumstances, the condition is commonly referred to as parturient paresis or milk fever. In cattle, hypocalcaemia is most prevalent in older dairy cows, e.g. at the third or later calving; this tendency has been attributed to reduced production or utilization of 1,25-dihydroxycholecalciferol, rather than failure to release PTH.

In sheep, hypocalcaemia most commonly occurs 2 to 4 weeks before lambing, but may occur from about 2 months before to 1.5 months after lambing. It is most likely to occur in ewes carrying more than one fetus. Even with dietary calcium supplementation, a ewe may lose as much as 20 percent of skeletal calcium during late pregnancy and early lactation. Such considerations underline the importance of bone resorption mechanisms to help meet the sudden increase of calcium demand during late pregnancy and early lactation, rather than attempting to rely only on dietary calcium.

As in sheep, hypocalcaemia in goats may occur before parturition, but in high-producing dairy goats, hypocalcaemia may be more prevalent after lactation has begun. Unless adequately supplemented, vitamin D levels can be quite low in livestock by spring at higher latitudes or in housing, and this can contribute to heightened hypocalcaemia risk where lambing or calving occurs in the spring.

For many years, hypocalcaemia in dairy cattle was often prevented by somewhat reducing calcium intake in late pregnancy, to stimulate PTH formation and consequent 1-hydroxylation of 25-hydroxycholecalciferol, in order to enhance absorption of dietary calcium and resorption of skeletal calcium. In recent years, adjustment of dietary cation and anion balances to raise 1,25-dihydroxycholecalciferol (i.e. 1,25-(OH)₂-D₃) concentration in plasma has been recommended as an alternative for dairy cows and has also proven effective in sheep. This method works by acidification's effect on sensitivity of the kidney to PTH, to increase 1-hydroxylation of 25-hydroxycholecalciferol. In routine management, appropriateness of the cation-anion balance can be inferred by monitoring urine pH.

Symptoms of hypocalcaemia in sheep may include restlessness, apparent blindness, recumbency, convulsions, and tetany. Death occurs in about 55 percent of cases. Symptoms closely resemble those of pregnancy toxaemia, and both conditions may be present in the same animal. Because the condition of a hypocalcaemic animal may deteriorate quickly, prompt administration of calcium is commonly done as a precaution for individuals presenting with such symptoms, rather than waiting for blood calcium analysis to provide differential diagnosis.

Common treatment for acute hypocalcemia in cows and sheep is intravenous injection of calcium gluconate (or calcium borogluconate) at a dose of 1 g calcium per 45 kg body mass), over a 10- to 20-minute period while performing cardiac auscultation. In mild cases, a calcium propionate oral drench may be administered, avoiding the risk of cardiotoxic effects that may be associated with intravenous administration.

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.

See also

• Calcium metabolism
• Hypercalcaemia
• Calcium deficiency (plant disorder)
• Hypomagnesemia with secondary hypocalcemia
• 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