Calcium metabolism and disorders

Role of calcium , metabolism and its disorders

1. Calcium metabolism Dr.S. Sethupathhy .,M.D., Ph.D ., Professor & Head, Dept. of Biochemistry. RMMC, AU

2. excitability of cell membranes neuromuscular transmission and muscle contraction releasing of transmitters from synapses “second messenger ” stimulates secretory activity of exocrine glands and releasing of hormones contractility of myocardium blood coagulation Calcium Importance

3. Hypocalcemia Muscle tetany , carpopedal spasm Dilatation of heart Increased cell membrane permeability Impaired blood clotting Hypercalcemia Depression of nervous system, reflex activity, Increased heart contractility Formation of calcium phosphate crystals Calcification, renal stones

4. 99% of skeletal calcium forms stable bone (not exchangeable with the Ca in extracellular fluid) 1% is in the form of releasable pool of Ca Balance of deposition and resorption Osteoblasts – bone-forming cells responsible for bone deposition Secrete type I collagen Differentiate into osteo c ytes Osteoclasts – “bone-eating” cells that resorb the previously formed bone Bone- reservoir of calcium

5. Bone cells

6. Bone remodelling

7. Free is physiologically active regulated by the combined actions of parathyroid hormone and calcitriol Changes in plasma [albumin] can alter total [ calcium] ‘ adjusted/corrected [calcium]’ for any abnormality of [albumin adjusted [ calcium] mmol /l= (measured [calcium] + 0.02(40 – [ albumin g/l])) Plasma free and total calcium

8. Stimulation PTH 1,25 Dihydrocholecalciferol IL-1 T3, T4 hGH , IGF-1 ( insuline -like growth factor) PGE 2 ( prostaglandin) TNF (tumor necrosis factor) Estrogens ? Inhibition Corticosteroids Osteoblasts

9. Stimulation PTH (not directly – through stimulation of osteoblasts) 1,25 Dihydrocholecalciferol (not directly – through stimulation of osteoblasts) IL-6, IL-11 Inhibition Calcitonin (directly – receptors) Estrogens (by inhibiting production of certain cytokines) TGF- β ( tranforming growth factor) PGE 2 (prostaglandin) Osteoclasts

10. Parathyroid glands polypeptide of 84 amino acids stimulus for secretion – low plasma calcium function – to INCREASE plasma calcium activation of osteoclasts – stimulates absorption of Ca , P from bones decreases excretion of Ca by kidneys increases excretion of P by kidneys stimulates conversion of vitamin D to calcitriol (vitamin D hormon ) in kidneys Parathormone

11. Parafollicular cells of thyroid gland (C-cells) peptide of 32 amino acids stimulus for secretion – high plasma calcium (food intake – gastrin , CCK, glucagon) function – to DECREASE plasma calcium and phosphates inhibits osteolysis – decreases absorption of Ca , P from bones stimulates incorporation of Ca , P to bones decreases absorption of Ca , P in kidneys decreases the effect of PTH on bones – PTH antagonist Calcitonin

12. Hypovitaminosis RICKETS ( rachitis )– children OSTEOMALACIA - adults ( less calcium) Osteoporosis is decrease of bone mass (matrix and minerals) Hypervitaminosis Tissue and organs calcification Loss of body weight Kidney function failure Vitamin D

13. Ca – Daily Requirements Age/ sex Ca (mg) 1-3 350 4-6 450 7-10 550 11-18 M 1000 11-18 F 800 19 + 700

14. Ca – Dietary Sources Milk – 100 ml =120mg Cheese – 15gm = 110mg Yoghurt pot – 80gm = 160mg Other sources Fish Meat Bread Cereal Broccoli

15. Urine Ca /Cr > 0.56 mmol / mmol <0.56 mmol / mmol Hypocalcaemic hypercalciuria Serum P Low High Vitamin D related causes Serum 25 OH D Serum 1, 25 (OH) 2 D VDDR Type I VDDR Type II Low Normal Low High Serum PTH Low High Vit D Deficiency Hypo- para - thyroidism Pseudo-hypo- para - thyroidism

16. Absorption is taking place from the first and second part of duodenum against concentration gradients Absorption required a carrier protein , helped by Ca -dependent ATPase Increased absorption- - calcitriol , active form of Vit -D - PTH - acidic pH - Lys and Arg Inhibiting absorption - - phytic acid - oxalates - phosphate - Mg caffeine - Calcium absorption

17. Picture quiz

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