1. Calcium & Phosphate Metabolism Calcium homeostasis Calcium in blood & cells  or  Ca 2+ — consequences: short term long term Roles of gut, bone, kidney Roles of:parathyroid hormone, vitamin D hormone, calcitonin Integrated responses Phosphate metabolism

2. Calcium 1.1 kg Ca 2+ — most (99%) in bone & teeth Blood Ca 2+ (mmol/L) ECF Ca 2+ (mmol/L) Cell Ca 2+ cytoplasm (  mol/L) Blood Ca 2+ Total 2.3 – 2.5 mmol/L diffusible & also complexed ionised  50% [ Ca 2+ ] protein bound  46%

3.  &  Ca 2+ Consequences depend on: a) severity b) whether a sudden or long term change

4.  Ca 2+ short term  Na + permeability of cells partial depolarisation muscle spasm tetany pins & needles seizures

5.  Ca 2+ short term  Na + permeability of cells hyperpolarisation neurologic dysfunction cardiac arrythmias constipation anorexia nausea Long term: kidney calcification & stones + Ca 2+ induced diuresis (  urine flow) dehydration

6. Serum Inorganic Phosphate PO 4 3- 0.8 – 1.4 mmol/L higher in kids exact regulation: less important than Ca 2+ high PO 4 3- :long term: soft tissue mineral deposition low PO 4 3- :long term: inadequate bone mineralisation

7. diet source GutBloodBone cells Kidney reabsorptionfiltered b) alternative store a) structural requirement for Ca/PO 4 Modulates losses urine Parathyroid hormone Vitamin D hormone = calcitriol = 1,25 dihydroxy vitamin D Calcitonin

8. Parathyroid Hormone PTH Peptide Parathyroid glands Release1.  by low Ca 2+ via calcium sensing receptor 2.  by calcitriol 3.  by high Ca 2+

9. Calcitriol = 1,25(OH) 2 D 7 dehydrocholesterol Vitamin D 25(OH) vitamin D 1, 25(OH) 2 D = calcitriol skin uv liver kidney  byPTH (low Ca 2+ ) low PO 4 3- growth pregnancy regulated

10. Calcitonin peptide parafollicular cells C cells of thyroid gland released bygastric hormones pentagastrin  Ca 2+

11. Gut ingested Ca 2+ & PO 4 3- (dairy foods) absorption: Ca 2+ small fraction passive active absorption:  by calcitriol, also PO 4 3- main function of calcitriol is to acquire Ca 2+ & PO 4 3- from food for bone mineral (PO 4 3- is relatively abundant)

13. Bone Calcium & Phosphate required for bone mineral (hydroxyapatite) compressive strength Acts as store of calcium (& phosphate) bone turnover Cont...

14. coupling Protein matrix + mineral (calcium and phosphate) deposited releasing calcium and phosphate

15. Short term release: Ca 2+ & PO 4 3- from bone  by:PTH Calcitriol* Inhibition of release by calcitonin * but main function is  Ca 2+ & PO 4 3- from diet bone

16. Kidney modulates Ca 2+ & PO 4 3- losses Ca 2+ filtration — depends on blood Ca 2+ conc. If [Ca 2+ ] is high  high filtered load (high loss Ca 2+ loss in urine) reabsorption (> 98%)  Ca 2+ reabsorption by PTH

17. Kidney PO 4 3- filtered reabsorbed to transport maximum PTHreduces PO 4 3- reabsorption causes PO 4 3- dumping in urine  PO 4 3-  PO 4 3- reabsorption PTH  calcitriol production

18.  blood Ca 2+  PTH a)  calcitriol b) conserve Ca 2+ c) dump PO 4 3- Bone  resorption g) release Ca 2+ h) release PO 4 3- blood Gut d)  Ca 2+ absorption e)  PO 4 3- absorption So because of different PTH effects in kidney (b & c) extra Ca 2+ being pumped into blood will be conserved, i.e. blood Ca will rise to normal extra PO 4 3- being pumped into blood will be dumped in urine, i.e. blood PO 4 3- remains unchanged

19. Gut  Ca 2+ & PO 4 3- absorption major effect blood Bone  resorption release of Ca 2+ & PO 4 3- minor effect no PTH, so no conservation of Ca 2+  PO 4 3- kidney  PO 4 3- losses tends to conserve PO 4 3-  calcitriol direct extra Ca 2+ filtered urine blood calcium unchanged extra PO 4 3- into blood tends to be conserved

20. Mineral metabolism cells bloodgutbone kidney PTH maintenance of blood Ca 2+ calcitriol Ca 2+ & PO 4 3- from diet bone