All done here! Check out our other subjects!
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
- Intracellular signalling pathways
The majority of calcium found in adults is stored in bone as hydroxyapatite crystals. The skeleton is a major reserve of calcium, and acts to buffer serum calcium levels through releasing calcium phosphate into the interstitium when required (serum calcium levels are normally between 2.2-2.6mM). Dairy is the main source of dietary calcium.
In plasma, calcium exists in one of three forms;
- As a free ionised species (biologically active calcium)
- Associated with serum proteins at their anionic sites (particularly albumin)
- Complexed with low-molecular-weight organic anions
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 of the parathyroid glands, which are separate glands usually on the posterior surface of the thyroid. Within chief cells, prepro-PTH is processed to pro-PTH and then 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 distinct from precursor maturation within the gland. PTH increases renal calcium reabsorption, stimulates renal production of calcitriol, and promotes bone resorption, 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. It acts at PTH receptors, increasing bone resorption and renal calcium reabsorption. Hypercalcaemia in cancer can also result from local osteolytic bone disease, including in myeloma; these mechanisms should not be conflated. Hypercalcaemia warrants assessment of the underlying cause.
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 in the kidney. PTH stimulates this renal step. Calcitriol increases intestinal absorption of calcium and phosphate and supports bone mineralisation. It is the precursor vitamin D, rather than calcitriol, that requires activation.
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 causes hyper-excitability of the neuromuscular junction. Symptoms include pins and needles, muscle cramps, tetany, and convulsions.
Hypercalcaemia can lead to renal calculi, kidney damage, constipation, dehydration, tiredness, and depression, remembered by the phrase "stones, moans, and groans"
- Stones - renal calculi (kidney stones)
- Moans - depression and tiredness
- Groans - constipation
Edited by: Dr. Marcus Judge
- 22906
