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Calcium and Vitamin D Metabolism and Related Diseases

Calcium and Vitamin D Metabolism and Related Diseases. Objectives. Calcium functions and metabolism Vitamin D functions and metabolism Vitamin D and calcium homeostasis Regulation of vitamin D synthesis Hypocalcaemia and hypercalcaemia Biochemistry, types and diagnosis of:

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Calcium and Vitamin D Metabolism and Related Diseases

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  1. Calcium and Vitamin D Metabolism and Related Diseases

  2. Objectives • Calcium functions and metabolism • Vitamin D functions and metabolism • Vitamin D and calcium homeostasis • Regulation of vitamin D synthesis • Hypocalcaemia and hypercalcaemia • Biochemistry, types and diagnosis of: • Rickets and osteoporosis

  3. Introduction • Bone is a specialized mineralized connective tissue • osteoclasts mobilize minerals • osteoblasts control mineralization of the newly synthesized matrix • calcium and phosphate in the form of hydroxyapatite and small amount of hydroxide and carbonate)

  4. CALCIUM • Calcium is the most abundant mineral in the body: • (1 kg) in a 70 kg man. • ~99% of the body’s calcium is present in the bone, where it is combined with phosphate .

  5. Biological function of calcium • Bone formation • Reservoir for ECF [Ca2+] •  99 % in bone • Clotting Total Calcium • ECF • Excitability of nerve & muscle • 1 % • Metabolic regulation for action of hormones & enzyme activation • ICF

  6. Calcium homeostasis

  7. Calcium balance: • In adults: normally, calcium intake = output . • In infancy and childhood:input > outputpositive balance , due to active skeletal growth. • In old age: calcium output > inputnegative balance; marked in women after menopause, postmenopausal osteoporosis.

  8. Sources of calcium: • Excellent: milk, cheese, yoghurt; • Fair (legumes, vegetables)

  9. Regulation of Calcium • PTH • 1,25 DHCC • Calcitonin Plasma [Ca2+] is regulated by:

  10. Parathyroid hormone (PTH) • PTH is the principal acute regulator of plasma [Ca2+].

  11. VitaminD A group of sterols with a hormone-like function. Calcitriol (1, 25 diOH cholecalciferol = 1, 25 diOH D3) is the biologically active molecule. Vitamins D2 & D3 Preformed Vitamin D in the diet: they are needed only in exposure to sunlight is limited. They are also available as supplement They are NOT biologically active They are activated in vivo to the biologically active form Recommended dietary allowance (RDA): 5 mg cholecalciferol = 200 IU of vit D3 (or more)

  12. D2, plant source D3, animal source: fatty fish, liver, egg yolk Lippincott’s Illustrated Reviews, Biochemistry, 4th Edition, Champe, Harvey and Ferrier

  13. Vitamin D metabolism • Cholecalciferol is derived from 7-dehydrocholesterol in the skin by sunlight In liver: • Cholecalciferol is converted to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase In kidneys: • The 1-alpha-hydroxylase enzyme converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (biologically active) • Active vitamin D is transported in blood by gc-globulin protein

  14. VITAMIN D SYNTHESIS SKIN LIVER KIDNEY 7-DEHYDROCHOLESTEROL VITAMIN D3 25(OH)VITAMIN D 25-HYDROXYLASE 1a-HYDROXYLASE UV VITAMIND3 25(OH)VITAMIN D 1,25(OH)2 VITAMIN D Predominant form in plasma ACTIVE METABOLITE Active vitamin D is transported in blood by vitamin D-binding protein

  15. Vitamin D functions • Regulates calcium and phosphorus levels in the body (calcium homeostasis) • Through: • Increasing uptake of calcium by the intestine • Minimizing loss of calcium by kidney • Stimulating resorption of bone when necessary Deficiency of 1: 25-DHCC  defective bone mineralization.

  16. Calcitonin • Calcitonin is • a peptide hormone • secreted by the parafollicular or “C” cells of the thyroid gland • released in response to high plasma calcium • Net result of its action  plasma calcium & phosphate

  17. Calcitonin : The only Hypocalcemic hormone • Calcitonin  plasma [Ca2+] by: •  osteoclast activity •  renal reabsorption of calcium and phosphate.

  18. Hypocalcaemia • Causes of hypocalcaemia: • Hypoprotenemia • Hypoparathyroidism • Vit D deficiency • Acute pancreatitis • Renal disease • Drugs as phenytoin and diphosphonates

  19. Symptoms: • Numbness around the mouth • Cramps and tetany • Laryngospasm • Cataract

  20. Hypercalcaemia • Causes of hypercalcaemia: • Artifact • Parathyroid disease, ( primary , tertiary hyperparathyroidism) • Malignant disease ( bone metastasis , multiple myeloma) • Drugs as lithium • Thyrotoxicosis

  21. Biochemical bone diseases • Generalized defects in bone mineralization, frequently associated with abnormal calcium or phosphate metabolism, "biochemical or metabolic bone diseases". Osteoporosis Rickets Osteomalacia The most common

  22. Osteomalacia and Rickets • Osteomalacia: • Defective bone mineralization in adults • Rickets: • Defective bone and cartilage mineralization in children • Before introduction of vitamin D-supplemented milk, children with insufficient exposure to sunlight developed Vit D deficiency • Not common these days as foods (milk, oils) are now supplemented with vitamin D

  23. Osteomalacia and Rickets, continued.. • These conditions are due to: • Vitamin D deficiency • Impaired vitamin D metabolism • Calcium deficiency • Imbalance in calcium homeostasis

  24. Osteomalacia and Rickets, continued.. • Vitamin-D-dependent rickets types 1 and 2 (genetic disorders) • Rare bone diseases • Due to: • Defects in vitamin D synthesis: type 1 (can be overcome by high doses of Vit D) • Defects in vitamin D receptor: type 2 (cannot be overcome by high doses of Vit D, as the hormone is unable to act)

  25. Osteomalacia and Rickets, continued.. Clinical features Rickets • Soft bones • Bone pain • Increased tendency of bone fractures • Skeletal deformity (bowed legs) • Muscle weakness • Dental problems • Growth disturbance Osteomalacia • Soft bones • Bone pain • Bone fractures • Compressed vertebrae • Muscle weakness

  26. Osteomalacia and Rickets, continued.. • Diagnosis • Serum calcium (hypocalcemia) • PTH secretion •  Alkaline phosphatase •  Serum levels of 25-hydroxycholecalciferol

  27. Osteoporosis • Reduction in bone mass per unit volume • Bone matrix composition is normal but it is reduced • Post-menopausal women lose more bone mass than men (primary osteoporosis)

  28. Osteoporosis • Secondary osteoporosis may be caused by: • Drugs • Immobilization • Smoking • Alcohol • Cushing’s syndrome • Gonadal failure • Hyperthyroidism • GI disease

  29. Osteoporosis, continued.. Diagnosis • Serial measurement of bone density • No specific biochemical tests to diagnose or monitor primary osteoporosis • Secondary osteoporosis (due to other causes) can be diagnosed by biochemical tests • The test results overlap in healthy subjects and patients with osteoporosis • Common biochemical tests: • Urinary Hydroxyproline (bone resorption) • Alkaline phosphatase (bone formation) • Osteocalcin (bone formation) Biochemistry Diagnosis is Unremarkable in Osteoporosis

  30. THANK YOU

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