calcium metabolism handout

7-dehydrocholesterol Previtamin D3

Solar UVB radiation

Skin

Vitamin D3Diet

25-hydroxylase

25(OH)-D

1-OHase

1,25(OH)2-D

PTH effects on the kidney1.Stimulates 1-OHase.2.Decreases PO4 resorption in proximal tubule via

increase in intracellular (and urinary) cAMP.3.Increases Ca resorption in distal tubule.

1,25(OH)2-D effects on kidneyIncreases Ca resorption in distal tubule, by upregulating calbindin.

1α-hydroxylationStimulated by Inhibited by PTH 1,25(OH)2-D Low PO4 High PO4

Possibly GH and insulin

Extra-renal 1α-hydroxylation in macrophages, e.g. in sarcoidosis.

Dietary Vit DAverage daily intake 500 iU.Recommended intake 400 iU.

25(OH)-D25-hydroxylase activity is essentially unregulated. 25(OH)-D is the major circulating metabolite, acting as a store.

PTH effects on boneActs on osteoblast cell membrane to increase permeability to calcium, activating a pump which drives calcium into ECF

PTH productionMain stimulus is low Ca2+.Inhibited by 1,25(OH)2-D.Mg required for synthesis, release and action of PTH.

Response to hypocalcaemiaRise in PTH, causing:• increased renal Ca absorption;• increased renal PO4 excretion;• mobilization of calcium and PO4 from bone;• increased 1α-hydroxylation, causing:

• increased GI absorption of calcium and PO4.

Response to hypophosphataemiaStimulates 1α-hydroxylation, causing:• increased GI absorption of PO4 and calcium;• rise in calcium inhibits PTH release, causing:

• increased renal PO4 resorption;• reduced renal calcium resorption.

Vitamin D replacementErgocalciferol = Vit D2

Cholecalciferol = Vit D3

Alfacalcidol = 1α(OH)-D3

Calcitriol = 1,25(OH)-D3

Calcitonin productionMain stimulus is high Ca2+ (ionized>1.15) – also glucagon, gastrin, ß-adrenergic agonists (?reason for low Ca in acute illness)

Calcitonin effects on bone• inhibits osteoclast resorption• thereby lowers Ca and PO4

• no effect on Mg

1,25(OH)2-D effects on gutIncreases Ca2+ and PO4

absorption by upregulating intracellular calbindin proteins.

Vit D effects on bone?Unsure if direct effect

Calcitonin

Parathyroid hormone