Calcium is one of the most abundant minerals in the human body, with over 99% of it stored within the bones and teeth to provide structural strength. The small fraction of calcium circulating in the bloodstream is electrically charged, acting as an electrolyte fundamental to life processes. It is necessary for the proper function of nerve cells, allowing impulse transmission, and plays a direct role in muscle contraction, including the rhythmic beating of the heart. Calcium is also required for blood clotting. The body must maintain serum calcium levels within a very narrow range of approximately 8.8 to 10.4 milligrams per deciliter, as even slight deviations can disrupt these electrical and mechanical functions. Calcium metabolism is the intricate process of hormonal and organ-based signaling that ensures this precise concentration is upheld, and a disorder results when this delicate balance is lost.
How the Body Regulates Calcium
The tight control of calcium balance, known as homeostasis, is overseen primarily by two hormones: parathyroid hormone (PTH) and the active form of Vitamin D, known as calcitriol. Parathyroid hormone is secreted by four small parathyroid glands located in the neck, and its release is triggered immediately when blood calcium levels begin to fall. PTH acts on three target organs—the bone, the kidney, and the intestine—to rapidly raise the calcium concentration back to normal.
In the skeletal system, PTH stimulates specialized cells called osteoclasts to resorb bone tissue, releasing stored calcium directly into the bloodstream. PTH also acts on the kidneys to increase the reabsorption of filtered calcium from the urine, preventing its loss. Furthermore, PTH acts on the kidneys to convert the inactive form of Vitamin D into the active hormone, calcitriol.
Calcitriol primarily targets the small intestine, enhancing the absorption of dietary calcium. This coordinated effort ensures the body quickly responds to fluctuations and maintains calcium stability. A third hormone, calcitonin, produced by the thyroid gland, acts to lower blood calcium levels by inhibiting bone breakdown, but its role in adult calcium homeostasis is less significant than PTH and calcitriol.
Hypercalcemia: Causes and Symptoms of High Calcium Levels
Hypercalcemia is an abnormally elevated level of calcium in the blood, often resulting from a disruption in the body’s regulatory feedback loops. The most frequent cause of high calcium in people living outside of hospitals is primary hyperparathyroidism, typically caused by an adenoma, a non-cancerous tumor, in one of the parathyroid glands. The tumor secretes excessive PTH independent of the body’s needs, forcing the release of calcium from the bones and increasing its reabsorption by the kidneys.
The second most common cause, and the leading cause in hospitalized patients, is malignancy (cancer). In many cancers, tumor cells secrete parathyroid hormone-related peptide (PTHrP), which mimics PTH by causing calcium release from bone. Metastasized cancers may also destroy bone locally, releasing high concentrations of calcium. Less common causes include excessive intake of Vitamin D supplements or certain medications.
The clinical manifestations of hypercalcemia are often subtle and non-specific, but they can affect nearly every organ system. Symptoms are frequently grouped into a classic mnemonic describing the impact on the renal, skeletal, gastrointestinal, and neurological systems. The renal effects, known as “stones,” involve increased urination and thirst, which can lead to dehydration, and the formation of kidney stones from precipitated calcium salts.
The skeletal effects, known as “bones,” result from continuous bone tissue breakdown, causing bone pain, weakening, and an increased risk of fractures. Gastrointestinal symptoms, or “groans,” include nausea, vomiting, constipation, and reduced appetite. The nervous system effects, or “psychiatric overtones,” involve fatigue, muscle weakness, confusion, memory problems, and depression.
Hypocalcemia: Causes and Symptoms of Low Calcium Levels
Hypocalcemia is a below-normal level of calcium in the blood, most commonly linked to issues with the parathyroid glands or Vitamin D metabolism. The most direct cause is hypoparathyroidism, where the parathyroid glands do not produce sufficient PTH. This deficiency often occurs following thyroid or parathyroid surgery due to accidental damage, or it may be caused by autoimmune destruction.
Without adequate PTH, the bone cannot be signaled to release calcium, the kidney cannot effectively conserve it, and Vitamin D activation is impaired. A second frequent cause is Vitamin D deficiency or resistance, which limits the intestinal absorption of dietary calcium. Low Vitamin D levels are common in individuals with limited sun exposure or malabsorption disorders.
Chronic kidney disease is another significant cause, as the damaged kidneys are unable to convert inactive Vitamin D into its active form, calcitriol. Furthermore, chronic kidney failure often leads to the retention of phosphate, which binds tightly to calcium in the blood, lowering the circulating free calcium level. Magnesium deficiency can also contribute to low calcium by impairing the secretion and action of PTH.
The defining characteristic of hypocalcemia is increased neuromuscular excitability, as the low calcium concentration makes nerve and muscle cells more prone to spontaneous firing. Patients commonly experience paresthesias, which are tingling and numbness sensations, particularly around the mouth, fingers, and toes. More severe hypocalcemia leads to tetany, characterized by painful, involuntary muscle spasms and cramps.
Two specific physical signs demonstrate this heightened excitability. Chvostek’s sign is elicited by lightly tapping the facial nerve in front of the ear, resulting in an involuntary twitch of the facial muscles. Trousseau’s sign, a more specific indicator, is demonstrated by inflating a blood pressure cuff on the upper arm above systolic pressure for a few minutes. The resulting lack of blood flow causes a carpopedal spasm, characterized by the wrist and hand flexing distinctly.