Describe the distribution, absorption and hormonal regulation of calcium. Give its functions and the disorders of calcium metabolism.

Distribution and Normal Values

• Corrected calcium — add 0.8 mg/dL for every 1 g/dL that albumin falls below 4 g/dL. Essential in hypoalbuminaemia, or true hypocalcaemia will be over-diagnosed
• Alkalosis lowers ionised calcium by increasing protein binding — the reason hyperventilation causes tetany with a normal total calcium

Absorption

• Absorbed chiefly in the duodenum and jejunum, by an active vitamin D-dependent route and by passive diffusion at high intake
• Only about 20–40% of dietary calcium is absorbed

Hormonal Regulation

↓ Serum ionised calcium → Detected by the calcium-sensing receptor of the parathyroid → ↑ PTH secretion → Bone resorption + renal reabsorption + ↑ calcitriol → ↑ gut absorption → Serum calcium restored

Functions

• Bone and teeth — as hydroxyapatite, Ca10(PO4)6(OH)2
• Blood coagulation — factor IV; needed by the vitamin K-dependent factors to bind phospholipid
• Muscle contraction — binds troponin C; excitation–contraction coupling
• Nerve conduction and neurotransmitter release
• Second messenger — with calmodulin; the IP3 pathway
• Enzyme activation — phosphorylase kinase, PDH phosphatase, lipase
• Secretion of hormones, and cell adhesion and division

Phosphorus

• 85% in bone; the rest intracellular
• Functions — ATP and all high-energy compounds, nucleic acids, phospholipids, 2,3-BPG, phosphorylation of proteins, and the urinary buffer
• Absorbed readily; excretion is controlled by PTH and FGF-23
• Hypophosphataemia — refeeding syndrome, alcoholism, DKA treatment; causes muscle weakness, haemolysis and respiratory failure

Disorders of Calcium

Excretion and Balance

• Urinary calcium 100–300 mg/day; the kidney reabsorbs about 98% of the filtered load
• PTH increases renal calcium reabsorption in the distal tubule, while increasing phosphate excretion in the proximal tubule
• Thiazides reduce urinary calcium (used in hypercalciuric stone formers); loop diuretics increase it (used in hypercalcaemia)
• Faecal calcium exceeds urinary, since most dietary calcium is never absorbed
• Bone acts as the buffer — it releases calcium when intake fails, which is why serum calcium stays normal long after the diet has become inadequate

Applied Aspects

• Rickets and osteomalacia — defective mineralisation from vitamin D deficiency; alkaline phosphatase is markedly raised
• Osteoporosis — loss of both mineral and matrix, with normal biochemistry; diagnosed by bone density, not by blood tests
• Renal osteodystrophy — failure of 1α-hydroxylation with phosphate retention → secondary hyperparathyroidism. Needs calcitriol, not plain vitamin D
• Tetany after thyroidectomy follows inadvertent removal of the parathyroids — check calcium in the first 24–48 hours
• Hypocalcaemia resistant to calcium is usually due to hypomagnesaemia, which impairs both PTH release and its action; correct the magnesium first