Section 12. Disorders of Nutrition and Metabolism

Chapter 155. Minerals and Electrolytes

Topics: Introduction | Calcium | Copper | Fluoride | Iodine | Iron | Magnesium | Phosphate | Potassium | Selenium | Sodium | Zinc

Calcium

Most of the body's calcium is stored in the bones, but calcium is also found in cells (particularly muscle cells) and in the blood. Calcium is essential to muscle contraction and to the normal functioning of many enzymes. It is necessary for the formation of bone and teeth, for blood clotting, and for normal heart rhythm.

The body precisely controls the amount of calcium in the cells and the blood. Maintaining a normal level of calcium in the blood depends on consuming at least 1,000 to 1,500 milligrams of calcium a day and excreting excess calcium in urine. Calcium moves out of the bones into the bloodstream as needed to maintain a steady level of calcium in the blood. However, mobilizing too much calcium from the bones weakens them and can lead to osteoporosis.

The level of calcium in the blood is regulated primarily by two hormones: parathyroid hormone and calcitonin. Parathyroid hormone is produced by the four parathyroid glands, located around the thyroid gland in the neck. When the calcium level in the blood falls, the parathyroid glands produce more parathyroid hormone. When the calcium level in the blood rises, the parathyroid glands produce less hormone. Parathyroid hormone stimulates the digestive tract to absorb more calcium and causes the kidneys to activate vitamin D. Vitamin D further enhances the ability of the digestive tract to absorb calcium. Parathyroid hormone also stimulates the bones to release calcium into the blood and causes the kidneys to excrete less calcium in urine. Calcitonin, a hormone produced by cells of the thyroid gland, lowers the calcium level in the blood by slowing the breakdown of bone.

Hypocalcemia

In hypocalcemia, the level of calcium in the blood is too low. Most of the calcium in the blood is carried by (bound to) the protein albumin. Albumin-bound calcium acts as a reserve but has no active function in the body. By contrast, unbound (ionized) calcium affects the body's functions. Thus, a low level of albumin in the blood usually causes no problems as long as the amount of unbound calcium remains normal. The total calcium level in the blood usually parallels the level of unbound calcium.

Hypocalcemia is most commonly caused by excessive calcium loss in the urine or a failure to move calcium out of the bones into the bloodstream. Hypocalcemia may result when the level of parathyroid hormone is low (for example, if the parathyroid glands are damaged during thyroid gland surgery), when a person is born without parathyroid glands, or when the body responds poorly to a normal level of parathyroid hormone (pseudohypoparathyroidism). A low level of magnesium may cause hypocalcemia by reducing the activity of parathyroid hormone. Other causes of hypocalcemia include vitamin D deficiency (due to poor nutrition or inadequate exposure to sunlight), kidney damage (which increases loss of calcium in urine and reduces the kidneys' ability to activate vitamin D), inadequate intake of calcium in the diet, disorders that affect calcium absorption, and pancreatitis.

The calcium level in the blood can be moderately low without producing any symptoms. Over time, hypocalcemia can affect the brain and cause neurologic or psychologic symptoms, such as confusion, memory loss, delirium, depression, and hallucinations. These symptoms are reversible if the calcium level is restored. An extremely low calcium level may cause tingling (often in the lips, tongue, fingers, and feet), muscle aches, spasms of the muscles in the throat (leading to difficulty breathing), stiffening and spasms of muscles (tetany), and abnormal heart rhythms.

Hypocalcemia is often detected by routine blood tests before symptoms become obvious.

Oral calcium supplements are often all that is needed to treat hypocalcemia. Once symptoms appear, intravenous administration of calcium is usually warranted. Taking vitamin D supplements helps increase the absorption of calcium from the digestive tract.

Hypercalcemia

In hypercalcemia, the level of calcium in the blood is too high. Hypercalcemia is commonly caused by hyperparathyroidism (the excessive secretion of parathyroid hormone by one or more of the four parathyroid glands).

Another cause of hypercalcemia is the ingestion of large amounts of calcium. Occasionally, hypercalcemia develops in people with peptic ulcers if they drink a lot of milk and take calcium-containing antacids for relief. The resulting disorder is called the milk-alkali syndrome. An overdose of vitamin D can also affect the calcium level in the blood by greatly increasing the absorption of calcium from the digestive tract.

Hypercalcemia often occurs in people who have cancer. Cancers of the kidneys, lungs, and ovaries may secrete large amounts of a protein that has effects similar to those of parathyroid hormone. These effects are considered a paraneoplastic syndrome (see Section 15, Chapter 181). Calcium can also be released into the blood when cancer spreads (metastasizes) to bone and destroys bone cells. Such bone destruction occurs most commonly with cancers of the prostate, breast, and lung. Multiple myeloma (a cancer involving bone marrow) can also lead to the destruction of bone and result in hypercalcemia. Other cancers can raise the calcium level in the blood by means not yet fully understood.

See the sidebar What Is Hyperparathyroidism?

Disorders in which bone is broken down (resorbed) or destroyed, causing calcium to be released, may also cause hypercalcemia. In Paget's disease, bone is broken down, but the calcium level in the blood is usually normal. However, the calcium level can become too high if people with the disease become dehydrated or spend too much time sitting or lying down--when the bones are not bearing weight. Rarely, other people who are immobilized, such as paraplegics, quadriplegics, or people who require prolonged bed rest, develop hypercalcemia because calcium in bone is released into the blood when the bones do not bear weight for long periods of time.

Hypercalcemia often produces no symptoms. The earliest symptoms are usually constipation, nausea, vomiting, abdominal pain, loss of appetite, and abnormally large amounts of urine. Very severe hypercalcemia often causes brain dysfunction with confusion, emotional disturbances, delirium, hallucinations, and coma. Muscle weakness may occur, and abnormal heart rhythms and death can follow. Kidney stones containing calcium may form in people with chronic hypercalcemia.

Hypercalcemia is usually discovered during routine blood tests.

If the hypercalcemia is not severe, correcting the cause is often sufficient. People who have normal kidney function and a tendency to develop hypercalcemia are usually advised to drink plenty of fluids, which stimulates the kidneys to excrete calcium and helps prevent dehydration.

If the calcium level is very high or if symptoms of brain dysfunction or muscle weakness appear, fluids and diuretics are given intravenously as long as kidney function is normal. Dialysis is a highly effective, safe, reliable treatment, but it is usually reserved for people with severe hypercalcemia that cannot be treated by other methods.

Several other drugs (including plicamycin, gallium nitrate, calcitonin, bisphosphonates, and corticosteroids) can be used to treat hypercalcemia. These drugs work primarily by slowing the release of calcium from bone.

Hypercalcemia caused by cancer is particularly difficult to treat. If the cancer cannot be controlled, hypercalcemia usually returns despite the best treatment.