calcium metabolism handout

7- dehydrocholeste rol Previtamin D 3 Solar UVB radiation Skin Vitamin D 3 Die t 25- hydroxylase 25(OH)- D 1-OHase 1,25(OH) 2 - D PTH effects on the kidney 1.Stimulates 1-OHase. 2.Decreases PO 4 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 PO 4 High PO 4 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 PO 4 excretion; • mobilization of calcium and PO 4 from bone; • increased 1α-hydroxylation, causing: • increased GI absorption of calcium and PO 4 . Response to hypophosphataemia Stimulates 1α-hydroxylation, causing: • increased GI absorption of PO 4 and calcium; • rise in calcium inhibits PTH release, causing: • increased renal PO 4 resorption; • reduced renal calcium resorption. Vitamin D replacement Ergocalciferol = Vit D 2 Cholecalciferol = Vit D 3 Alfacalcidol = 1α(OH)-D 3 Calcitriol = 1,25(OH)-D 3 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 PO 4 • no effect on Mg 1,25(OH) 2 -D effects on gut Increases Ca 2+ and PO 4 absorption by upregulating intracellular calbindin proteins. Vit D effects on bone? Unsure if direct effect Calcitoni n Parathyroi d hormone

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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