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Core
Calcium is one of the most important ions in the body, having many functions:
- Regulation of heart rhythm
- Maintaining muscle function
- Maintaining kidney function
- Maintaining nerve function
- Maintaining bones and teeth
- Influences blood clotting, blood pressure, and cholesterol
- Hormone and enzyme activity
- Signalling pathways inside cells (intracellular signalling)
The majority of calcium found in adults is stored in bone as hydroxyapatite crystals (a hard calcium phosphate mineral). The skeleton is a major reserve of calcium. It acts to buffer serum calcium levels through releasing calcium phosphate into the interstitium (the fluid-filled space between cells) when required. Total serum calcium is normally about 2.2 to 2.6 mmol/L (millimoles per litre, also written mM). Dairy foods are a common source of dietary calcium. Others include green leafy vegetables, bread and other foods made with fortified flour, soya drinks with added calcium, and fish eaten with the bones.
In plasma (the liquid part of blood), calcium exists in three forms at the same time. Only the free ionised form is biologically active. The other two forms still count towards the total calcium reading, which is why low albumin lowers total calcium:
- As a free ionised species (calcium carrying its electrical charge and not bound to anything; this is the biologically active calcium)
- Associated with serum proteins at their anionic (negatively charged) sites (particularly albumin)
- Complexed with low-molecular-weight organic anions (small negatively charged molecules, for example citrate and phosphate)
Three hormones are involved in the regulation of calcium: parathyroid hormone, calcitriol, and calcitonin.
Parathyroid hormone (PTH) raises serum calcium. It is synthesised in the chief cells (the hormone-making cells) of the parathyroid glands, which are four small, separate glands usually on the posterior surface of the thyroid. Within chief cells, PTH is first made as a larger earlier form (prepro-PTH), which is trimmed to pro-PTH and then to mature PTH before secretion. Low ionised calcium stimulates PTH release; higher calcium suppresses it. Circulating PTH is short-lived and is broken down mainly in the liver and kidneys. This breakdown is separate from the trimming of the earlier forms inside the gland. PTH increases renal calcium reabsorption, stimulates renal production of calcitriol, and promotes bone resorption (breakdown of bone by osteoclasts), releasing calcium from bone into the blood. Its effect on intestinal calcium absorption is indirect, through calcitriol.
Parathyroid hormone-related peptide (PTHrP) can be secreted by some tumours and cause humoral hypercalcaemia of malignancy (humoral means carried in the blood; hypercalcaemia means high blood calcium; malignancy means cancer). It acts at PTH receptors, increasing bone resorption and renal calcium reabsorption. Hypercalcaemia in cancer can also result from local osteolytic bone disease (bone destruction next to the tumour), including in myeloma (a cancer of the plasma cells in bone marrow); these mechanisms should not be conflated. Hypercalcaemia needs its cause found. The two most common causes are primary hyperparathyroidism (overactive parathyroid glands) and malignancy (cancer). Severe hypercalcaemia (adjusted serum calcium above 3.5 mmol/L) needs emergency referral to hospital.
Calcitriol (1,25-dihydroxyvitamin D) is the active form of vitamin D. Vitamin D obtained from skin synthesis, food or supplements is converted first to 25-hydroxyvitamin D in the liver, then to calcitriol by 1-alpha-hydroxylation (adding a hydroxyl group, which is an oxygen and hydrogen pair) in the kidney. PTH stimulates this renal step. Calcitriol increases intestinal absorption of calcium and phosphate and supports bone mineralisation (laying down calcium and phosphate in bone). Vitamin D itself is inactive and needs these two conversions, whereas calcitriol is already the active form.
Calcitonin is secreted by the parafollicular (C) cells of the thyroid. It inhibits osteoclast-mediated bone resorption and can lower serum calcium, but it has a relatively minor role in normal adult calcium homeostasis compared with PTH and calcitriol.
Diagram: Simplified calcium regulation by parathyroid PTH and thyroid calcitonin. The parathyroid glands are separate glands usually on the posterior surface of the thyroid. PTH and calcitriol are the main regulators; calcitonin has a minor role in normal adults.
SimpleMed Original by Dr. Marcus Judge
Hypocalcaemia (low blood calcium) causes hyper-excitability of the neuromuscular junction (where a nerve meets a muscle). Symptoms include pins and needles, muscle cramps, tetany (painful, sustained muscle spasm), and convulsions.
Hypercalcaemia can lead to renal calculi (kidney stones), kidney damage, bone pain, tummy pain, constipation, dehydration, tiredness, and depression, remembered by the phrase "stones, bones, groans, and moans".
- Stones - renal calculi (kidney stones)
- Bones - bone pain
- Groans - constipation and tummy pain
- Moans - depression and tiredness
Edited by: Dr. Marcus Judge
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