﴿و ما أوتيتم من العلم إلا قليلا﴾ بسم الله الرحمن الرحيم ﴿و ما أوتيتم من العلم إلا قليلا﴾ صدق الله العظيم الاسراء اية 85

Assist Prof of Medical Physiology Calcium Homeostasis By Dr. Abdel Aziz M. Hussein Assist Prof of Medical Physiology

Functional histology of bone

Structure of Bone Bone cells Matrix Bone Osteoblasts Osteoclasts Osteocytes Matrix Organic e.g. Collagen Inorganic e.g. CaPO4 Bone

Bone Cells Osteoblast Osteoclast Osteocyte Bone forming cells Secrete bone matrix or collagen Contain alkaline phosphatase (help CaPO4 deposition) Osteoclast Bone eating cells (Large multinucleated cells derived from monocytes) Help bone resorption and destruction Contain acid phosphatase which produce lactic and hyaluronic acid Osteocyte Mature bone cells Most numerous cells Cannot form collagen

Bone Cells Osteoclast

Body fluids (ICF and ECF) Total Body Ca+2 1000 – 1200 gm (70 Kg adult man) Bone and Teeth (99%) (1000 g) Body fluids (ICF and ECF) (1%) (1 g)

Plasma Ca+2 concentration 9 – 11 mg/dl Non-diffusible (45%) (bound with albumin) Diffusible (55%) Complexed with PO4 (10%) Ionized (45%) Active part

Un-exchangeable Ca+2 pool Calcium Homeostasis Ca+2 intake Un-exchangeable Ca+2 pool Exchangeable Ca+2 pool Ca+2 loss

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.

Physiological importance of Ca+2 4. Essential for neurotransmission 5. Essential for ms contraction 6. Essential for blood clotting. 7. Essential for formation of bone and teeth.

Hormonal Control of Plasma Ca+2 PTH Vitamin D Calcitonin Other hormones

Parathyroid Hormone

Parathyroid Hormone (PTH) Source: Chief cells of parathyroid gland Chemistry: Polypeptide hormone (84 aa)

Functions of PTH The 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).

Functions of PTH PCT Osteoblast Osteoclast

Functions of PTH a) Kidney: Increases reabsorption of Ca+2 and Mg+2 from DCT Inhibits PO4 reabsorption from PCT. Activates Vit. D by 1 α hydroxylase enzyme in PCT b) Bone: Increases number and level of activity of osteoclasts (bone destroying cells) in the skeleton →bone resorption Increases pump of Ca+2 from bone matrix to ECF by osteoblast a) 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.

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

Thyrocalcitonin

Thyrocalcitonin Source: Parafollicular cells of thyroid gland Chemistry: Polypeptide hormone (32 aa) Thyrocalcitonin

Thyrocalcitonin Functions: ↓Blood Ca+2

Functions of calcitonin Is the physiological antagonist to PTH with respect to Ca+2 i.e. lowers blood Ca+2 Has the same effect of PTH on PO4 i.e. ↓es PO4 level Has no effect on plasma Mg level.

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.

Control of Calcitonin secretion i)Plasma Ca+2: The major stimulus to its secretion is a rise in serum Ca+2 e.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.

Vitamin d3

Vitamin D3 Biosynthesis: Formed in skin by UVR Activated at liver and kidney to form 1,25 DOCC

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-.

Other hormones

Sex Hormones Sex hormones are involved in the pubertal growth spurt and closure of the epiphyses a)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

Glucocorticoids At 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.

Growth hormone Thyroid hormone Stimulate bone growth Stimulate Ca+2 and PO4 absorption from intestine Thyroid hormone Stimulate bone growth and ossification Hypothyroidism delay bone growth and hyperthyroidism causes bone resorption

Disorders of ca+2 homeostasis

Disorders of Ca+2 Homeostasis Disturbances of Ca+2 homeostasis Hypercalcemia As in hyperparathyroidism and bone tumours Hypocalcemia As in hypoparathyroidism and lack of vit D Rickets, osteomalacia Tetany

Hyperparathyroidism

Signs and symptoms Hypocalcaemia and Tetany

Signs and symptoms Hypocalcaemia and Tetany

Rickets and Osteomalacia

Osteoporosis

Thank You