Hypercalcemia

Hypercalcemia (hypercalcaemia) means elevated calcium level in the blood. It can be a serious condition followed by a number of complications.

 

Calcium is essential for body structure and many biochemical processes. Calcium in the bones ensures their integrity; it is involved in transmission of nerve impulses to the muscles and in the blood clotting process.

 

Blood calcium has normal concentration approximately from 8.5-10.2 mg/dL (2.2-2.6 mmol/L). Half of this amount is free and the other half is bound to blood proteins. However, the largest amount of calcium is not in the blood, but in the bones, which are the main body reservoir of calcium ions.

Calcium metabolism

The blood concentration of calcium and its homeostasis is a complicated issue involving many factors. The calcium blood level is increased by parathyroid hormone and vitamin D and reduces by a hormone known as calcitonin. Parathyroid hormone is produced in the parathyroid glands, which are four small “balls” in the thyroid gland. Parathyroid hormone can increase serum calcium by increased disintegration of bone tissue and by increased production of vitamin D.

 

Vitamin D may be ingested with food, but the majority is produced by our own body. Vitamin D production is a complex process that takes place in kidneys, liver and skin. The whole process needs sunlight to be efficient. Vitamin D increases calcium absorption by the intestinal mucosa and somewhat inhibits its excretion by the kidneys.

 

The hormone calcitonin is also produced by parathyroid glands. It decreases calcium levels in the blood and thus works against the effect of parathyroid hormone.

 

Calcium level also depends on the function of kidneys (excretion of calcium into the urine), and the level of blood phosphate. Calcium and phosphate blood concentrations are in balance and that their product is constant. Elevation of blood phosphate decreases calcium level and vice versa.

Causes

I shall mention only the most common and clinically important causes of hypercalcemia.

Bone metastases

Hypercalcemia is sad complication of malignant diseases with metastatic spread to bones.  It is especially present in the so-called osteolytic tumors, whose metastases break down the bone tissue. Osteolytic behaviour is typical for example for breast cancer.

Immobilization

Long-term immobilization of the patient and inactivity of the musculoskeletal system leads to gradual decalcification of bones.

Multiple myeloma

This is a specific cancer based on white blood cells producing antibodies (B-lymphocytes). The tumor cells spread into the bones such as ribs and skull bones.

Hyperparathyroidism

Hyperparathyroidism is associated with increased production of parathyroid hormone by the parathyroid gland. There condition causes decalcification of bones and increase of calcium level in the blood. This situation is usually due to a benign tumor of the parathyroid gland, and only rarely due to malignant tumor.

Vitamin D overdose

Excessive intake of vitamin D may increase calcium level in the blood with all its negative consequences. Similar problem occurs in some diseases that cause production of vitamin D-like substances. It is for example the sarcoidosis and a number of malignant diseases.

Chronic kidney failure

This case is a little bit more complicated. Failing kidneys are unable to get rid of phosphate and its blood concentration rises. As I wrote above, the product of calcium and phosphate concentrations is constant and that is why the calcium concentration decreases (hypocalcemia). In order to increase the level of calcium, our body begins to produce more parathyroid hormone in parathyroid glands (we call this the secondary hyperparathyroidism). Excessively produced parathyroid hormone causes bone decalcification and increase of blood calcium level (rarely to hypercalcemia).

Symptoms

Symptoms of hypercalcemia may be relatively inconspicuous. The patient may complain of fatigue, muscle weakness and apathy. In the elderly it may even mimic dementia. Hypercalcemia also influences the motility of gastrointestinal tract resulting in constipation, nausea and more frequent vomiting. When there is a bone decalcification present, the patient may complain about bone pain and there is increased risk of pathologic fractures. In kidneys, calcium salts can form urinary stones that can cause renal colic and other complications. Perhaps the most important and serious is the effect of calcium on the heart muscle. The increased concentration of calcium can be followed by arrhythmias and including sudden cardiac arrest. Chronic hypercalcemia increases risk of peptic ulcers and acute pancreatitis.

 

It is appropriate to note that the tolerance of high level of blood calcium is individual. Rapid increase may cause serious symptoms, whereas slow and gradual increase may be quite well-tolerated.

Diagnosis

The diagnosis of hypercalcemia is easily done from a simple blood test. When the diagnosis is confirmed, it is advisable to thoroughly examine other parameters related to calcium metabolism (blood levels of vitamin D, parathyroid hormone, renal parameters, etc.). Parathyroid glands may be examined by ultrasound and bone metastases can be confirmed or excluded by bone scintigraphy. Further diagnostic approach depends on the outcome of previously mentioned examination procedures.

Treatment

In the first place it is necessary to solve the hypercalcemia and then to treat the underlying cause (if possible). Acute hypercalcemia can be treated by hydration (to dilute blood minerals) and by diuretics (especially furosemide). In cases related to strong bone decalcification, it is possible to administer drugs known as bisphosphonates (drugs damping bone degradation) or the calcitonin hormone. When a very high level of calcium is unsolvable by conservative means, it is possible to perform an acute dialysis.