Regulation of calcium

Calcium in the human body is 99% hydroxyapatite in bone. The remaining 1% is a readily exchangeable pool in equilibrium with the ECF, comprising

1. 45% free calcium ("ionized calcium, iCa"), ~1.15mM - biologically active
2. 35% bound to albumin
3. 10% bound to globulin
4. 10% complexed with anions

Two hormones regulate iCa,

1. PTH (from parathyroid, released with \(\downarrow iCa \to\) decreased binding to CSR)
2. Calcitonin (from thyroid, released when \(\uparrow iCa\)

They do so by modulating

1. Absorption and excretion, partly by the vitamin D system
2. The bone reabsorption/formation balance

Hypocalcaemia \(\to\ \ \uparrow\) Ca absorption, \(\downarrow\) Ca excretion, \(\uparrow\) PO4 excretion, net bone formation, and vice versa for hypercalcaemia. Mechanistically,

$$\require{AMScd}$$

$$\begin{CD} @. {\uparrow \uparrow \substack{\text{Renal PO4} \\ \text{excretion}}} @. @. @. @. @. \\ @. @AAA @. @. \\ \text{Parathyroid} @>>> {\uparrow PTH} @>>> {\downarrow \downarrow \substack{\text{Renal Ca} \\ \text{excretion}}} @. @. \\ @A{stimulates}AA @VVV @AAA @. \\ \mathbf{\downarrow iCa} @. {\uparrow \substack{\text{25OH-D} \\ \text{hydroxylation}}} @>>> {1,25OH\text{-vitD}} @>>> {\uparrow \substack{\text{GI Ca} \\ \text{reabsorption}}} \\ @V{inhibits}VV @AAA @VVV @. \\ \text{Thyroid} @>>> {\downarrow \text{Calcitriol}} @. {\downarrow \substack{\text{Renal PO4} \\ \text{excretion}}} @. @. \end{CD}$$ and,

$$\begin{CD} \text{Parathyroid} @>>> {\uparrow PTH} @>{inhibits}>> \text{Osteoblasts} @. @. \\ @A{stimulates}AA @V{stimulates}VV @VVV @. \\ \mathbf{\downarrow iCa} @. \text{Osteoclasts} @>>> {\substack{\text{Net bone} \\ \text{reabsorption}}} @>>> {\uparrow PO4^-} \\ @V{inhibits}VV @A{disinhibits}AA @VVV @. \\ \text{Thyroid} @>>> {\downarrow \text{Calcitriol}} @. {\uparrow iCa} @. @. \end{CD}$$