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CALCIUM and PHOSPHORUS for medical students
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- 2. •Body distribution: Total Calcium:1-1.5 Kg Bones: 99% ECF: 1% •Dietary sources: Milk: cow = 100mg/dl human = 30 mg/dl Egg, fish , vegetables and cereals (ragi)
- 3. Daily requirement: Adults :500mg/day Children : 1200mg/day Pregnancy and lactation : 1500mg/day >50 years : 1500mg/day
- 4. Metabolism • Absorption: duodenum Mechanism •Transcellular pathway Active transport Calcium-dependent ATPase Requires calcium transporter / pump Saturable, unidirectional • Paracellular pathway passive diffusion non saturable, bidirectional
- 5. Factors affecting absorption absorption VitaminD PTH – on intestinal cells pregnancy lactation hypocalcemia Acidity Amino acids: Lysine and arginine
- 6. Decreased absorption •Phytic acid:Hexaphosphate of inositol is present in cereals. •Oxalates: calcium oxalates. •Malabsorption syndromes: insoluble calcium salt of fatty acid. •Phosphate: calcium phosphate. •calcium to phosphorus- 1:1 to 2:1 as present in milk. Factors affecting absorption
- 7. Excretion stool: 400 mg urine:100 – 200 mg Calcium dependent proteins Calmodulin: regulate enzyme activity Calbindin: calcium storage Calsequestrin: calcium storage Troponin C: modulates muscle contraction
- 8. Biochemical functions Mechanism ofaction Ca ++ + Calmodulin complex kinase (inactive) kinase (active) Enz Enz - P
- 9. Enzyme activation eg: •Adenyl cyclase •Ca++dependent protein kinases •Ca++ -Mg++ -ATPase •Glycerol-3-phosphate dehydrogenase •Glycogen synthase •Phospholipase C •Phosphorylase kinase •Pyruvate carboxylase •Pyruvate dehydrogenase •Pyruvate kinase
- 10. Nerve conduction •Transmission ofnerve impulses from presynaptic to postsynaptic region. Secretion of hormones • insulin, PTH, calcitonin, vasopressin. •Second messengers •Bone Osteoblasts and osteoclasts •Teeth formation
- 11. •Excitation and contractionof muscle fibers.
- 12. •Excitation and contractionof muscle fibers.
- 13. • Blood Coagulation- factor IV Ca binds to gamma-carboxylated residues activate clotting factors
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- 17. Blood level ofcalcium Total serum Ca = 9 – 11 mg/dl Forms: ionized Ca (free Ca) = 5 mg/dl Metabolically active It is diffusible from blood to tissues. protein bound Ca = 4 mg/dl complexed calcium = 1 mg/dl calcium complexed to citrate, HCO3, phosphate
- 19. • Protein boundcalcium calcium bounds with albumin (80%) globulin (20%) 1 gm of albumin binds with 0.8 mg of calcium Acidosis negative charge binding free Ca Alkalosis binding
- 20. Regulation of BloodCalcium Level Hormones Vitamin D increases Ca Parathyroid Hormone Calcitonin: decreases calcium 1. Vitamin D synthesis of calbindin Ca absorption
- 21. 2. Parathyroid hormone Kidney:calcitriol synthesis reabsorption of calcium phosphate excretion Bone: bone resorption causes demineralization increases osteoclasts
- 22. 3. Calcitonin •Increased by: calcium, gastrin Hypercalcitoninemin: Medullary carcinoma of thyroid. •Calcitonin decreases serum calcium level. inhibits bone resorption decreases osteoclasts increases osteoblasts
- 23. Regulation of BloodCalcium Level
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- 26. When to CheckCalcium Level? • Nephrosis • Renal calculi • Ectopic calcification • Suspected malignancies • Polyuria and polydypsia • Chronic renal failure • Prolonged drug treatment, which may cause hypercalcemia (vitamin D, thiazide diuretics)
- 27. Hypercalcemia •Serum calcium >11 mg/dl •Causes: 1) Hyperparathyroidism parathyroid tumor Ectopic PTH secreting tumor 2) Bone tumors Paget’s disease metastatic carcinoma multiple myeloma 3) Vitamin D toxicity
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- 30. •Clinical features bone fracture urinarystones muscle weakness •Lab diagnosis Blood: calcium alkaline phosphatase phosphate Urine: calcium
- 31. Parathyroid Function Tests •Serum calcium, phosphate and alkaline phosphatase. • Urinary calcium and phosphate levels. EDTA test: The normal level is re-established within 6-12 hours. Calcium load test: • Intravenous calcium will lower PTH levels in normal persons. In urine, calcium is excreted, no phosphates are seen. TRP (tubular reabsoption of phosphate) test: 90% of phosphates in glomerular filtrate are reabsorbed.
- 32. Hypocalcemia Causes • Hypoparathyroidism • Nephroticsyndrome loss of protein bound calcium • Acute pancreatitis deposition of calcium in necrotic tissues • Renal failure vitamin D synthesis
- 33. Deficiency of VitaminD • Decreased exposure to sunlight • Malabsorption, Hepatic diseases Deficiency of Calcium • Intestinal malabsorption • Acute pancreatitis • Infusion of agents complexing calcium • Alkalosis decreasing ionized calcium • Hypoalbuminemia
- 34. Clinical features • Serumcalcium < 8.5 mg/dl: tremors < 7.5 mg/dl: tetany Tetany: Parathyroid glands or autoimmune diseases. neuromuscular irritability carpopedal spasm laryngeal spasm Chovstek’s sign -tapping over facial nerve causes facial contraction
- 35. • Pseudohypoparathyroidism defect: lackof end organ response to PTH Lab diagnosis: PTH levels are normal calcium, phosphorus • Osteomalacia defective bone mineralization vitamin D deficiency
- 36. Bone Mineralization •calcium andphosphate are deposited on the organic matrix- Osteoid. •Osteocalcin, osteonectin, osteopontin and osteoprotegerin.
- 37. Osteoporosis • After theage of 40–45, calcium absorption is reduced and calcium excretion is increased; so, there is a net negative balance for calcium. • This is reflected in demineralization. • After the age of 60, osteoporosis is seen. • Then there is reduced bone strength and an increased risk of fractures. • Decreased absorption of vitamin D and reduced levels of androgens/estrogens in old age are the causative factors.
- 38. • Osteoporosis loss ofbone mass inadequate bone formation increased bone resorption causes: Decreased absorption of vitamin D Reduced levels of androgens/estrogens in old age Cushing’s syndrome Hyperparathyroidism Multiple myeloma
- 39. • High riskgroup: advanced age (> 50 years) females smoking • Clinical features bone fracture: vertebra, hip, forearm • Prevention : calcium intake (1 – 1.5 gm) vitamin D
- 40. Paget’s disease Localized diseaseof bone characterized by osteoclastic bone resorption followed by disordered replacement of bone. • Bone resorption • Bone pain • Secondary osteoarthritis • Bony deformity
- 41. Markers of bonediseases • Serum calcium, phosphorus, magnesium. • alkaline phosphatase and acid phosphatase levels. • urinary excretion of calcium and phosphorus. • Markers of bone resorption • tartrate resistant acid phosphatase (TRAP), urinary hydroxyproline excretion, type I collagen. • Markers of bone formation • Osteocalcin, osteonectin, osteopontin and osteoprotegerin.
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- 43. •Body distribution : Total:1kg 80% - bones and teeth, 10% - muscles. The whole blood phosphate is 40 mg/dl •Daily requirement: 500 mg/dl
- 45. •Sources: Milk (100 mg/dl) Cereals,nuts, meat
- 46. METABOLISM •Absorption : Jejunum Calcitriol:increases absorption Acidity increases absorption •Excretion: urine – 500 mg/day
- 48. Functions 1. Bone andteeth formation. 2. Production of high energy phosphate compounds. 3. Synthesis of nucleoside co-enzymes (NADP). 4. DNA and RNA synthesis 5. Formation of phosphate esters phospholipids phosphoproteins 6. Activation of enzymes phosphorylation of enzymes 7. Acid – base regulation: Phosphate buffer Na2HPO4 : NaH2PO4
- 49. Normal Blood Levels: •In adults : 3 - 4 mg/dl • In children: 5 - 6 mg/dl • Whole blood : 40mg/dl Forms • Ionic form (50%) • Complexed form (40%): Na, Ca, Mg • Protein bound form (10%) Phosphate level is regulated by excretion through urine.
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- 52. Fibroblast Growth Factor23 (FGF-23) •Inhibit the reabsorption of phosphate and the synthesis of 1,25(OH)(2)D. •Manifestations : hypophosphatemia, low 1,25(OH)(2)D levels, rickets
- 54. Hyperphosphatemia • Excess vitaminD • Increased cell lysis: leukemia, hemolysis, lymphoma Chemotherapy for cancer Bone secondaries Rhabdomyolysis Decreased excretion of phosphorus • Renal impairment • Hypoparathyroidism • Hypocalcemia • Blood transfusions Drugs-Chlorothiazide, Nifedipine, Furosemide
- 55. Hypophosphatemia Increased phosphate excretion •Hyperparathyroidism Decreased intestinal absorption • Vitamin D deficiency • Malabsorption Increased intestinal loss • Vomiting • Diarrhea • Insulin therapy, Respiratory alkalosis. • Chronic alcoholism • Drugs-Antacids, Diuretics, Salicylate intoxication
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