Describe the regulation of plasma calcium. Explain the actions of parathyroid hormone, vitamin D and calcitonin.

Normal Values and Distribution

• Total body calcium 1–1.5 kg; 99% in bone
• Daily requirement 0.5–1 g (1.5 g in pregnancy and lactation)
• Acidosis → ↑ ionised calcium; alkalosis → ↓ ionised calcium → tetany, even with a normal total calcium

Functions of Calcium

• Bone and teeth — structural
• Muscle contraction — binds troponin C / calmodulin
• Neurotransmitter and hormone release — exocytosis is Ca2+-dependent
• Blood coagulation — factor IV
• Second messenger — with calmodulin
• Membrane excitability — stabilises the membrane; a fall causes hyperexcitability

Parathyroid Hormone

• Net effect — ↑ plasma calcium, ↓ plasma phosphate
• Secretion is controlled by ionised calcium acting on a calcium-sensing receptor; a fall stimulates PTH within minutes
• Bone effect is biphasic — intermittent low-dose PTH is actually anabolic, which is why teriparatide treats osteoporosis

Vitamin D

7-dehydrocholesterol in skin → UV light → Cholecalciferol (vitamin D3) → liver — 25-hydroxylase → 25(OH)D3 → kidney — 1α-hydroxylase (stimulated by PTH, ↓ phosphate) → 1,25(OH)2D3 — calcitriol

• Actions — ↑ calcium and phosphate absorption from the gut (via calbindin); ↑ renal reabsorption; permits bone mineralisation
• 25(OH)D3 is measured to assess vitamin D status — it has the longest half-life
• The kidney step is rate-limiting, which is why renal failure causes hypocalcaemia

Calcitonin

• From parafollicular (C) cells of the thyroid
• Secreted in response to hypercalcaemia
• Action — inhibits osteoclasts → ↓ plasma calcium and phosphate. Opposes PTH
• Of minor importance in the adult — neither thyroidectomy nor medullary carcinoma disturbs calcium appreciably. More important in growth and in pregnancy

Summary of the Three Hormones

Bone Remodelling

• PTH acts on the osteoblast, not the osteoclast — it induces RANKL, which activates osteoclast precursors. Osteoprotegerin is the natural decoy that blocks this
• About 10% of the skeleton is remodelled each year

Applied Aspects

• Hypocalcaemia → tetany — carpopedal spasm, Trousseau sign (cuff inflation), Chvostek sign (tapping the facial nerve), laryngospasm, convulsions
• Hypoparathyroidism — most often accidental removal during thyroidectomy → ↓ Ca, ↑ phosphate
• Primary hyperparathyroidism — adenoma → "stones, bones, abdominal groans and psychic moans"
• Rickets and osteomalacia — vitamin D deficiency; defective mineralisation with bowing of legs, rickety rosary and widened epiphyses
• Renal osteodystrophy — renal failure → ↓ calcitriol and phosphate retention → hypocalcaemia → secondary hyperparathyroidism
• Osteoporosis — loss of bone mass with normal mineralisation; postmenopausal (oestrogen deficiency) or senile; treated with calcium, vitamin D and bisphosphonates