4 Structure of Bone Bone cells Matrix Bone Osteoblasts Osteoclasts OsteocytesMatrixOrganic e.g. CollagenInorganic e.g. CaPO4Bone
5 Bone Cells Osteoblast Osteoclast Osteocyte Bone forming cells Secrete bone matrix or collagenContain alkaline phosphatase (help CaPO4 deposition)OsteoclastBone eating cells (Large multinucleated cells derived from monocytes)Help bone resorption and destructionContain acid phosphatase which produce lactic and hyaluronic acidOsteocyteMature bone cellsMost numerous cellsCannot form collagen
7 Body fluids (ICF and ECF) Total Body Ca+21000 – 1200 gm (70 Kg adult man)Bone and Teeth(99%) (1000 g)Body fluids (ICF and ECF)(1%) (1 g)
8 Plasma Ca+2 concentration 9 – 11 mg/dlNon-diffusible(45%)(bound with albumin)Diffusible(55%)Complexed with PO4(10%)Ionized(45%)Active part
9 Un-exchangeable Ca+2 pool Calcium HomeostasisCa+2 intakeUn-exchangeable Ca+2 poolExchangeable Ca+2 poolCa+2 loss
10 Physiological importance of Ca+2 Ca+2 has fundamental importance to all biological systems.Participates in numerous enzymatic reactions.Important for hormone secretion.Acts as a mediator of hormonal effects.
11 Physiological importance of Ca+2 4. Essential for neurotransmission5. Essential for ms contraction6. Essential for blood clotting.7. Essential for formation of bone and teeth.
12 Hormonal Control of Plasma Ca+2 PTHVitamin DCalcitoninOther hormones
15 Functions of PTHThe prime function of PTH is to keep a normal Ca+2 level in plasma (9-11 mg %).It also maintains a constant ratio between Ca+2 and inorganic phosphate PO4-, so that;Solubility product = Ca x PO4 = K (constant).
17 Functions of PTH a) Kidney: Increases reabsorption of Ca+2 and Mg+2 from DCTInhibits PO4 reabsorption from PCT.Activates Vit. D by 1 α hydroxylase enzyme in PCTb) Bone:Increases number and level of activity of osteoclasts (bone destroying cells) in the skeleton →bone resorptionIncreases pump of Ca+2 from bone matrix to ECF by osteoblasta) Small intestine :Increases absorption of Ca+2 (mediated by active vitamin D (1, 25 DOH cholecalciferol)→ activated in the kidney by PTH.Increases absorption of PO4 and Mg+2.
18 Control of PTH secretion 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
22 Functions of calcitonin Is the physiological antagonist to PTH with respect to Ca+2 i.e. lowers blood Ca+2Has the same effect of PTH on PO4 i.e. ↓es PO4 levelHas no effect on plasma Mg level.
23 Functions of calcitonin a) Bones:Inhibits osteolysis by osteocytes and reduces resorption by osteoclasts.Decreases Ca+2 mobilization from bone to blood as it inhibits Ca+2 permeability of bone cells.b) Kidneys:Increases urinary excretion of Ca+2 and PO4.Inhibits Vit. D activation in the kidney.c) Intestine:Decreases Ca+2 absorption from the intestine.Inhibits the gastric motility and gastrin secretion.
24 Control of Calcitonin secretion i)Plasma Ca+2:The major stimulus to its secretion is a rise in serum Ca+2e.g. its plasma concentration ↑es 2-10 times after acute rise of serum Ca+2 of as little as 1 mg%.ii) GIT hormones:Several GIT hormones (gastrin is the most potent) stimulate calcitonin secretion during ingestion of food.
26 Vitamin D3 Biosynthesis: Formed in skin by UVR Activated at liver and kidney to form 1,25 DOCC
27 Action of Vitamin D The intestine is the principal target of vitamin D a)On intestine:Stimulates the absorption of both Ca+2 and PO4-.b)On bone:Bone is the 2nd major target of vitamin D.Provides Ca+2 and PO4- to initiate the crystallization of bone osteoid at bone surfaces.c)On kidney:Increases renal tubular reabsorption of both Ca+2 and PO4-.
29 Sex HormonesSex hormones are involved in the pubertal growth spurt and closure of the epiphysesa)Estrogens:Protect female skeleton from the development of osteoporosis:Inhibits PTH mediated bone resorption↓es the amount of bone-resorbing cytokines such as interleukin 1 and 6 in bone.↑es serum PTH due to the hypocalaemic effect of the inhibition of bone resorption.b)Androgens;Protect men from the development of osteoporosis
30 GlucocorticoidsAt physiological levels, glucocorticoids are necessary for skeletal growth.Chronic excess have deleterious effects on Ca+2 homeostasis)Decrease renal tubular Ca+2 absorption.Inhibit intestinal Ca+2 absorption.Inhibit osteoblastic bone formation.
31 Growth hormone Thyroid hormone Stimulate bone growthStimulate Ca+2 and PO4 absorption from intestineThyroid hormoneStimulate bone growth and ossificationHypothyroidism delay bone growth and hyperthyroidism causes bone resorption
33 Disorders of Ca+2 Homeostasis Disturbances of Ca+2 homeostasisHypercalcemiaAs in hyperparathyroidism and bone tumoursHypocalcemiaAs in hypoparathyroidism and lack of vit DRickets, osteomalaciaTetany