Calcium Regulation

Normal Calcium: 25,000 mmol (400 mmol/kg)

Distribution:

• Readily exchangeable pool (1%) (ECF esp plasma)
  • Total plasma [Ca2+] = 2.12-2.65 mmol/L
  • Ionised [Ca2+] = 1.2 mmol/L
    • Only the plasma free Ca is physiologically active and regulated by homeostatic mechanisms
  • Two pools
    • Diffusible (55%)
      • 45% free/ionised
        • Active form (above)
      • 10% complexed
    • Non-diffusible (45%)
      • protein bound (esp to albumin)
      • pH-dependent (↑ binding with ↑ pH)
• Poorly exchangeable pool (99%)
  • Bone/teeth (as hydroxyapatite, phosphates, carbonates)

Calcium balance

ECF and hence plasma Ca is the result of a balance between dietary intake, gastrointestinal absorption and excretion, renal excretion and exchange with bone Ca.

Normal Losses:

• Kidneys (40%) → 2.5-7.5 mmol/day
  • Filtration of 250 mmol/day
  • 95% reabsorbed by tubules
    • PCT 65% with Na
    • TAL of LoH 20%
    • distal nephron 10%
  • 5% excreted
  • ↑ reabsorption at LoH/distal nephron
    • PTH
    • 1,25-dihydroxy-vitamin D
• GIT in faeces (60%) → 6-14 mmol/day

Calcium Regulation

1. Calcitonin
   • 32 AA peptide with 1 disulfide bond it is the hormone of Procalcitonin
   • Released from Parafollicular cells (C-cells) of thyroid
   • Release Stimuli: Hypercalcaemia, gastrin, beta-agonists, dopamine, oestrogen, CCK, glucagon and secretin
   • Effect:
     • Increases osteoblast function/Inhibits osteoclast function
     • ↓intestinal calcium reabsorption
     • inhibition of renal Ca and PO4 reabsorption
2. Vitamin D
   • Fat soluble sercosteroid from either
     • diet or
     • synthesis in skin of cholecalciferol from cholesterol then processed in liver and activated in PCT of the kidney
   • Release stimuli
     • ↑ concentration of PTH causes ↑ 1-alpha-hydroxylase activity in kidney or ↓ Ca or PO4
   • Effect:
     • ↑ bone release of Ca/PO4
     • ↑ intestinal and renal reabsoption of Ca and PO4
     • negative feedback on PTH release
3. Parathyroid hormone
   • Polypeptide hormone secreted from the parathyroid gland
   • Release stimuli:
     • ↓ Ca (primary or due to ↑ PO4) sensed by CaSR (Ca sensing receptor) in PT chief cell
     • ↓ vitamin D levels
   • Effect:
     • ↑ Ca/PO4 reabsorption due to ↑ osteoclast activity
     • ↑ Vit-D production by kidney (effect on 25 alpha hydroxylase)
     • ↑ illeal Ca reabsorption
     • ↑ renal reabsoption of Ca/Mg from DCT and TAL loop of henle
     • ↓ PCT phosphate reabsorption

Gladwin 2016

Answer by Gladwin