( Source, Release & Function ) 1.structure of bone & teeth 2.neurotransmission 3. blood clotting 4. muscle contraction 5. hormonal actions 6. hormone secretion Total Body Calcium 1100 g 1% Body fluids 99% Bone and teeth (skeleton) 9 - 11 mg% 60% Diffusible 50% Ionized active form 10% Non-Ionized 40% Non-Diffusible Bound to protein as albumin Exchangable Ca+2 pool Un-exchangable Ca+2 pool • There are 3 types of bone cells: 1. Osteoblasts are the differentiated bone forming cells and secrete bone matrix on which Ca++ and PO precipitate. 2. Osteocytes, the mature bone cells are enclosed in bone matrix. 3. Osteoclasts is a large multinucleated cell derived from monocytes whose function is to resorb bone. • These cells are responsible for Bone remodeling which is a process which continues throughout life, long after epiphyseal fusion and cessation of linear growth of bone. • Remodeling consists of bone formation and bone resorption. They are 4 in number and each gland is 3-5 mm in diameter. Polypeptide hormone 84 aa. PTH controls calcium within the blood in a very tight range between 9.0 and 11 mg/dl. It also maintains a constant ratio ( ) Ca and inorganic phosphate PO4-, so that; Solubility product = Ca x PO4 = K (constant). Ca and PO4 are, thus, inversely related. PTH tends to raise the lowered Ca level by acting on;. Chief cells Serum calcium - Parathormone Ca++ absorption Ca++ reabsorption Ca++ bone resorption a) Kidney: • i) It ↑es the reabsorption of Ca and Mg from the renal tubules. • ii) It ↑es PO4 excretion. • iii) It activates Vit. D by 1 α hydroxylase enzyme. b) Bone: • It ↑es the number and level of activity of osteoclasts (bone destroying cells) in the skeleton → results in bone resorption → release of Ca into the blood stream and hypercalcaemia. a) Small intestine : • a) It ↑es the absorption of Ca (mediated by active vitamin D (1, 25 DOH cholecalciferol)→ activated in the kidney by PTH. • b) It ↑es the absorption of PO4 and Mg. • a) Plasma Ca level: • It the main regulator of PTH secretion. • ↓ Plasma Ca level → ↑ PTH secretion • b) Plasma Mg level: as Ca • c) Plasma PO4 level: opposite to Ca • d) Nervous factors: • β-adrenergic receptors agonists as isoproterenol→↑ PTH secretion Protein hormone (32 a.a) secreted by parafollicular cells or c-cells of the thyroid gland 1- The major stimulus to its secretion is a rise in serum Ca+2 due to increase intracellular cyclic AMP. 2- Ingestion of food stimulates it and this effect is mediated by GIT hormone of which gastrin is the most potent. 1-The major effect of calcitonin administration is a rapid fall in plasma Ca+2. Young growing animals are most affected, whereas in adults, who have more stable skeleton, only minimal response is seen. 2-It produce inhibition of osteolysis by osteocytes and reduce bone resorption by osteoclasts Ca+2 mobilization from bone to blood is also decreased, as calcitonin inhibit Ca+2 permeability of bone cells. 3-It is a physiological antagonist to parathormone with respect to Ca+2 , But has the same effect of parathormone on PO4 i.e. decrease plasma PO4 level, and has no effect on plasma magnesium level. 4-It increase urinary excretion of Ca+2 and PO4. 5-It also decrease Ca+2 absorption from the intestine. 6-can be used therapeutically for the treatment of hypercalcemia or osteoporosis. Vit. D has dietary and endogenous precursors: D2 (ergocalciferol) formed in plants D3(cholecalciferol) formed in skin 1-stimulate Ca+2 and phosphate reabsorption in intestine and kidney. 2-provide Ca+2 and phosphate needed for bone formation. 3-promote differentiation of monocyte precursor to monocytes and macrophage.