Calcium regulation and hypocalcaemia
Calcium homeostasis
The amount of calcium present in the extracellular fluid is very small in comparison to that stored in bone. Even in the adult, calcium in bone is not static; some bone is resorbed each day and the calcium returned to the ECF. To maintain calcium balance, an equal amount of bone formation must take place. Figure 35.1 shows how much calcium is exchanged between one compartment and another daily.
Fig 35.1 Normal calcium balance. Calcium is exchanged each day, in the amounts shown, between the extracellular fluid and the gut, bone and kidney.
Calcium homeostasis is modulated by hormones (Fig 35.2). Parathyroid hormone (PTH), which consists of 84 amino acids, is secreted from the parathyroid glands in response to a low unbound plasma calcium. PTH causes bone resorption and promotes calcium reabsorption in the renal tubules, preventing loss in the urine. 1,25-dihydroxycholecalciferol (1,25 DHCC) maintains intestinal calcium absorption. This sterol hormone is formed from vitamin D (cholecalciferol), following hydroxylation in the liver (at carbon-25) and kidney (at carbon-1). However, hydroxylation in the kidney is PTH dependent, and so even the absorption of calcium from the gut relies (albeit indirectly) on PTH.
Serum calcium
A healthy person has a total serum calcium of around 2.4 mmol/L. About half is bound to protein, mostly to albumin. Binding is pH dependent and is decreased in acidosis, because the amino acid side chains on albumin become more positively charged. Conversely, binding is increased if an alkalosis is present. Hence, the percentage of unbound calcium increases in acidosis and decreases if there is an alkalosis.
Unbound calcium is the biologically active fraction of the total calcium in plasma and maintenance of its concentration within tight limits is required for nerve function, membrane permeability, muscle contraction and glandular secretion. It is the unbound calcium concentration that is recognized by the parathyroid glands, and PTH acts to keep this concentration constant.
Laboratories routinely measure total calcium concentration (that is both the bound and unbound fractions) in a serum sample. However, this may give rise to problems in the interpretation of results because changes in serum albumin concentration cause changes in total calcium concentration. If albumin concentration falls, total serum calcium is low because the bound fraction is decreased (Fig 35.3