Dietary calcium enters the blood through the small intestine and exits in urine via the
kidneys. In the body, most calcium is located in bones, only about 1% is in the blood and
extracellular fluid. There is a continual exchange of calcium between blood serum and bone tissue.
The amount of calcium in circulation is mainly regulated by 2 hormones: parathyroid hormone, PTH,
and calcitriol. PTH is produced in the parathyroid gland while calcitriol is made in the kidney. When
serum calcium level is low, PTH is upregulated. PTH acts to promote calcium release from bones
and reduce calcium loss from urine. At the same time, it stimulates production of calcitriol,
which promotes absorption of calcium in the small intestine while also increases reabsorption in the
kidney. Together, they bring up calcium levels back to normal. The reverse happens when calcium
level is high. This feedback loop keeps serum calcium concentrations within the normal range.
Hypocalcemia refers to abnormally low levels of calcium in the blood and is generally defined as
serum calcium level lower than 2.1 mmol/L. Because the total serum calcium includes
albumin-bound and free-ionized calcium, of which only the latter is physiologically active,
calcium levels must be corrected to account for albumin changes. For example,
decreased albumin levels, such as in liver diseases, nephrotic syndrome, or malnutrition,
produce lower serum calcium values but the amount of free calcium may still be
normal. On the other hand, in conditions with high blood pH, albumin binds more calcium;
leaving less free-ionized calcium in the serum while the total calcium level may appear normal.
The most common cause of hypocalcemia is PTH deficiency resulting from decreased function of
the parathyroid glands, or hypoparathyroidism. Hypoparathyroidism, in turn, may be caused by
a variety of diseases and factors. These include: - accidental removal or damage of the parathyroid
glands during a surgery - autoimmune disorders
- congenital disorders: mutations that set the “normal calcium levels” to a lower value
- other genetic disorders that produce underdeveloped or non-functional
parathyroid glands - magnesium deficiency
Other causes of hypocalcemia include low vitamin D intake/production, and excessive loss of calcium
from the circulation such as in kidney diseases, tissue injuries or gastrointestinal diseases.
While chronic moderate hypocalcemia may be asymptomatic, acute and severe hypocalcemia
can be life-threatening. Most symptoms of acute hypocalcemia can be attributed to the effect it
has on action potential generation in neurons. Because extracellular calcium inhibits sodium
channels, and consequently depolarization, reduced calcium level makes it easier
for depolarization to occur. Hypocalcemia therefore increases neuronal excitability,
causing neuromuscular irritability and muscle spasms. Early symptoms often include numbness
and tingling sensations around the mouth, in the fingers and toes. As the disease progresses,
muscle spasms may manifest as tetany, wheezing, voice change, and dysphagia.
Seizures may occur in severe cases. Effects of hypocalcemia on cardiac function include long
QT interval due to prolonged ST fragment, congestive heart failure and hypotension.
Acute hypocalcemia should be treated promptly with intravenous calcium. Chronic hypocalcemia
is usually treated with oral calcium and possibly vitamin D supplementation.