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Calcium metabolism by Dr Anurag Yadav
- 1. CALCIUM METABOLISM Dr Anurag Yadav Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 Email: dranurag.y.m@gmail.com
- 2. A naturally occurring, homogeneous inorganic solid substance having a definite chemical composition and characteristic crystalline structure, color, and hardness. Dr Anurag Yadav
- 3. FUNCTIONS Medium for cell activity – muscle & nerve cell excitability, permeability of cell membrane. Involved in maintenance of body fluid They are structural elements in body – bone & teeth Minerals are part of physiological compounds --- Iron of Hb, Iodine of Thyroxine Cofactors of enzymes --- Dr Anurag Yadav
- 4. Cu- ceruloplasmin, tyrosinse Zn –DNA RNA Polymerase, Alc DH Iron – Cyt oxidase, catalase, peroxidase Mg –hexoKinase Se – Glu peroxidase Mo – xanthine oxidase Ni – urease Dr Anurag Yadav
- 5. Macrominerals Daily requirment > 100mg Microminerals / Trace elements Daily requirment < 100mg Dr Anurag Yadav
- 8. Total body calcium 1-1.5 Kg 99%-bone 1% ECF Source Milk – 100mg in 100mL Egg, Fish, Vegetables, Cereals Requirment Adult – 500mg/day Children – 1200mg/day Pregnancy Lactation – 1500mg/day Elderly – 1500mg/day + Vit D – 20microgm/day Dr Anurag Yadav
- 9. ABSORPTION Duodenum Active transport Requires calcium binding protein Factors affecting absorption Soluble calcium present pH Calcium – phosphorus ratio Fat digestion & absorption PTH & Vit D Dr Anurag Yadav
- 10. Increased absorption Vit D – synthesis of Calbindin PTH – activate Vit D Acidity Amino acids – arginine and lysine Inhibit absorption Phytic acid - cereals Oxalates – leafy vegetables Malabsorption syndrome High phosphates = calcium- phosphate Chronic renal failure, Coeliac disease Dr Anurag Yadav
- 11. FUNCTIONS OF CALCIUM Intracellular Calcium Muscle contraction Initiated by binding of calcium to Troponine Release of hormones, neurotransmitter Influx of calcium from extracellular space into the neurons causes release of neurotransmitter into synaptic cleft by exocytosis Action of enzymes Calcium ions stabilize the active conformation of the enzyme Cell division Involved in Mitosis Dr Anurag Yadav
- 12. Extracellular Calcium Maintenance of intracellular calcium Calcium in bone acts as reservoir helps to maintain extracellular fluid calcium concentration Bone mineralization 99% is deposited as Hydroxyapatite crystal Blood coagulation Inactive prothrombin to active thrombin Membrane excitability Ca++ ions activate Na channels decreased Ca decreased Na channel activity – Tetany Membrane potential Dr Anurag Yadav
- 13. Calcium levels 9-11mg/dL 3 forms Free/ Ionic/Unbound calcium 50% ---- 5mg/dL metabolically active Bound 40% ---- 4mg/dL bound to albumin Complexed calcium 10% complexed with anions Bicarbonate, Phosphate, Citrate Dr Anurag Yadav
- 14. Regulation of Calcium levels 3 organs Bone Kidney Intestine 3 Hormones Parathyroid Vit D Calcitonin Dr Anurag Yadav
- 15. 3 processes Absorption of Calcium from the intestine – Vit D Reabsorption of Calcium from the Kidney – PTH & Vit D Demineralization of the bone --- PTH Dr Anurag Yadav
- 16. 1) Vitamin D Active form – 1, 25 dihydroxy cholecalciferol / Calcitriol In Intestine Absorption of Calcium from intestine Dr Anurag Yadav
- 17. In BONE Calcitriol stimulates osteoblasts Osteoblasts secrete Alkaline phosphatase Local concentration of phosphates is increased When ionic product of Calcium & Phosphorus increases MINERALIZATION takes place In RENAL TUBULES Increases the reabsorption of Calcium & Phosphorus Dr Anurag Yadav
- 18. 2) Parathyroid hormone PTH Secreted by parathyroid glands PTH secretion is controled by negative feed back by the ionized calcium in the serum Acts via cAMP Dr Anurag Yadav
- 19. PTH action on bones Demineralization Induces phosphatases in osteoclasts Osteoclasts release lactate in the surroundin– solubilizes calcium Increases secretion of Collagenase from osteoclast --- loss of matrix Dr Anurag Yadav
- 20. PTH action on Kidney Decrease renal excretion of calcium by increasing the reabsorption Increased renal excretion of Phosphates PTH action on Intestine Increases Calcium absorption via Vit D by activating Vit D Stimulates 1 hydroxylation in the Kidney Dr Anurag Yadav
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- 22. 3) Calcitonin Secreted by thyroid parafollicular cells Decrease Calcium levels Inhibits resorption of bone Decreases activity of osteoclasts & increases activity of osteoblasts Increases Excretion of Ca & Phosphorus Dr Anurag Yadav
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- 24. 4) Phosphorus Reciprocal relationship Ionic product of calcium & phosphorus is kept constant --- 40 Renal failure phosphorus excretion decreased --- increase in phosphorus & Ca level decreased 5) Children Upper limit Ionic product 50 Dr Anurag Yadav
- 25. 6) Serum proteins Hypoalbuminemia – decreased total calcium 0.8mg of Ca reduced per gm/dL decrease in albumin Metabolically active form normal 7) Alkalosis & Acidosis Alkalosis favours binding of Ca to proteins --- decrease in ionic Ca Acidosis favours ionization Dr Anurag Yadav
- 26. Hypercalcemia Ca >11mg/dL Causes Hyperparathyroidism Multiple myeloma Pagets disease Metastatic carcinoma of the bone Prolonged immobilization Drugs – thiazide diuretics – reabsorpion of Ca Excess Vit D , IV Ca Dr Anurag Yadav
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- 30. Symptoms Nausea, Vomiting Confusion, depression Osteoporosis Renal stones Ectopic calcification & pancreatitis Blood alkaline phosphatase is elevated Dr Anurag Yadav
- 31. Hypocalcimea Ca < 8.8mg/dL Ca levels <7.5 Tetany Causes Deficiency of Vit D Hypoparathyroidism Medullary carcinoma of thyroid – increased Calcitonin Decreased absorption Renal failure – increased phosphorus levels Hypoalbuminemia Dr Anurag Yadav
- 32. Symptoms Neuromascular irritability Muscle cramps Seizures Bradycardia Prolonged QT Interval Tetany Carpopedal spasm Laryngismus & stridor Chvostek’s sign +ve Trousseu’s sign +ve Dr Anurag Yadav
- 34. Hypocalcemia can be treated by Oral calcium with vitamin D supplementation Underlying cause should be treated. Tetany needs IV calcium (usually 10 mL 10% calcium gluconate over 10 minutes, followed by slow IV infusion. IV calcium should be given only very slowly. Dr Anurag Yadav
- 35. DISORDERS RELATED Osteoporosis Osteopetrosis Pagets disease Renal osteodystrophy Dr Anurag Yadav
- 36. OSTEOPOROSIS After the age of 40–45, calcium absorption is reduced and calcium excretion is increased there is a net negative balance for calcium. This is reflected in demineralization. After the age of 60, osteoporosis is seen. reduced bone strength and an increased risk of Fractures is seen in patients. Decreased absorption of vitamin D and reduced levels of androgens/estrogens in old age are the causative factors. Dr Anurag Yadav
- 37. Osteopetrosis It is otherwise called marble bone disease. There is increased bone density. It is due to mutation in gene encoding carbonic anhydrase type II. The deficiency of the enzyme in osteoclasts leads to inability of bone resorption. Paget’s Disease Localized disease of bone characterized by osteoclastic bone resorption followed by disordered replacement of bone. It is common in people above 40 and may affect one or several bones. Familial incidence is also reported. Bone markers are useful in monitoring response to treatment using bisphosphonates. Dr Anurag Yadav
- 38. Renal Osteodystrophy Secondary hyperparathyroidism as a consequence of persistent hypocalcemia causes high turnover bone disease, osteitis fibrosa. Osteomalacia may result (low bone turnover) due to defective synthesis of 1,25 DHCC Dr Anurag Yadav
- 39. MARKERS OF BONE DISEASE Metabolic bone diseases result from an imbalance between bone resorption and bone formation. Osteopenia is more common than excess bone formation. Dr Anurag Yadav
- 40. GENERAL MARKERS OF BONE DISEASE Serum Calcium, Serum Inorganic Phosphorus, Serum Magnesium And Urinary Excretion Of Calcium And Phosphorus, Total Alkaline Phosphatase And Total Acid Phosphatase Levels. These are the routine tests of bone metabolism. Vitamin D nutrition should be determined by measuring serum 25-hydroxy vitamin D. PTH measurement would be required if serum calcium is abnormal. Dr Anurag Yadav
- 41. Markers of bone resorption Markers of bone formation Telopeptide •Serum carboxy terminal telopeptide of type I collagen •N-telopeptide of type I collagen Serum bone specific isoenzyme of alkaline phosphatase (sBAP) Pyridinium cross links derived from collagen Serum osteocalcin (s-OC) Tartrate resistant acid phosphatase (TRAP) Serum midportion of osteocalcin (sm-OC) Urinary hydroxyproline excretion Procollagen type 1 peptidase Serum intact osteocalcin (s-OC) Serum amino-terminal propeptide of type I collagen (PINP) Dr Anurag Yadav
- 42. Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 Email: dranurag.y.m@gmail.com