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7-dehydrocholesterol Previtamin D3
Solar UVB radiation
Skin
Vitamin D3
Diet
25-hydroxylase
25(OH)-D
1-OHase
1,25(OH)2-D
PTH effects on the kidney
1.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 kidney
Increases Ca resorption in distal
tubule, by upregulating calbindin.
1α-hydroxylation
Stimulated 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 D
Average daily intake 500 iU.
Recommended intake 400 iU.
25(OH)-D
25-hydroxylase activity is essentially
unregulated. 25(OH)-D is the major
circulating metabolite, acting as a store.
PTH effects on bone
Acts on osteoblast cell
membrane to increase
permeability to calcium,
activating a pump which
drives calcium into ECF
PTH production
Main stimulus is low Ca2+.
Inhibited by 1,25(OH)2-D.
Mg required for synthesis,
release and action of PTH.
Response to hypocalcaemia
Rise 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 hypophosphataemia
Stimulates 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 replacement
Ergocalciferol = Vit D2
Cholecalciferol = Vit D3
Alfacalcidol = 1α(OH)-D3
Calcitriol = 1,25(OH)-D3
Calcitonin production
Main 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 gut
Increases Ca2+
and PO4
absorption by upregulating
intracellular calbindin
proteins.
Vit D effects
on bone?
Unsure if direct
effect
Calcitonin
Parathyroid
hormone

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Calcium metabolism handout

  • 1. 7-dehydrocholesterol Previtamin D3 Solar UVB radiation Skin Vitamin D3 Diet 25-hydroxylase 25(OH)-D 1-OHase 1,25(OH)2-D PTH effects on the kidney 1.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 kidney Increases Ca resorption in distal tubule, by upregulating calbindin. 1α-hydroxylation Stimulated 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 D Average daily intake 500 iU. Recommended intake 400 iU. 25(OH)-D 25-hydroxylase activity is essentially unregulated. 25(OH)-D is the major circulating metabolite, acting as a store. PTH effects on bone Acts on osteoblast cell membrane to increase permeability to calcium, activating a pump which drives calcium into ECF PTH production Main stimulus is low Ca2+. Inhibited by 1,25(OH)2-D. Mg required for synthesis, release and action of PTH. Response to hypocalcaemia Rise 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 hypophosphataemia Stimulates 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 replacement Ergocalciferol = Vit D2 Cholecalciferol = Vit D3 Alfacalcidol = 1α(OH)-D3 Calcitriol = 1,25(OH)-D3 Calcitonin production Main 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 gut Increases Ca2+ and PO4 absorption by upregulating intracellular calbindin proteins. Vit D effects on bone? Unsure if direct effect Calcitonin Parathyroid hormone