Calcium and Phosphorus Metabolism Dr. Rajeev Sharma

Functions of Calcium 1. Acts as an external guard of Na+ channels. 2. Necessary for normal neuronal function. 3. An important intracellular second messenger. 4. Necessary for muscle contraction. 5. Necessary for blood coagulation. So a very important cat ion for normal tissue function .

Functions of Phosphorus 1.Found in ATP,ADP,cAMP, 2,3-DPG, many proteins & vital compounds in the body. 2.Phosphorylation & dephosphorylation of proteins – involved in regulation of cell function. 3.Gives rigidity to bones & teeth. So an important anion for normal tissue function.

MAIN ORGANS INVOLVED They are : 1. G.I.T. 2. Kidneys. 3. Bones.

MECHANISM A triangle : G.I.T. E.C.F. BONES KIDNEYS

Distribution of calcium in human body Total body calcium – 1100g Plasma calcium –9.4 to10mg/dl (4.8 to 5.0 meq./ L or 2.4 to 2.5 mmol./L). 98.9% of body calcium is in bones 1% intracellular 0.1% extracellular fluid

Distribution of calcium in plasma 41% 1.0 mmol/L (Inactive) Diffusible 50% (1.2 mmol/L) (Active form) 9%(Di.) (0.2 mmol/L) (Citrates,Po4)(Inactive) Non Diffusible

ABSORPTION FROM G.I.T. 1.Occurs actively, mainly from duodenum. 2. Amount absorbed is exactly as much as is needed by the body. 3. Divalent cations on their own are poorly absorbed. 4. Under the influence of vit. D about 35%

Renal Handling of Calcium A. : CALCIUM – a. 59% of the plasma ca. is filtered. b. 99% of the filtered amount is reabsorbed. I.90% obligatory in :P.T.,L.H.,Early D.T. II.10% Selective in :Late D.T.,C.T.,C.D. ( Increased by P.T.H.)

Calcium Metabolism Diet Bones 1,000gms Exchangable 20gms GI Tract ECF (1000mg/day) Calcium Metabolism Bones 1,000gms GI Tract 1000 + 600 mg Vitamin D+ Absorption 700mg/day Exchangable 20gms ECF 1000 mg Calcitonin,+Vit.D Secretion 600mg/day 300mg Resorption (PTH,Vit.D +) Stable 980 gms 9900 mg PTH,Vit.D +(Cal- ), Glomerular Filtrate 10,000mg/ day Feces 900 mg/day Urine 100 mg/day

Distribution of BodyPhosphorus Total body phosphorus,500-800gm. 85% in skeleton,14-15% in I.C.F.,<1% in E.C.F. Total plasma phosphate 3 to 4mg/dl.

Intestinal absorption of phosphorus. 1. Some of it is lost in feces combined with non absorbed Ca. 2. Rest is easily absorbed.

Renal handling of phosphorus 1.Above renal threshold of 1 m.mol./ L, it is lost in urine. 2. It is strongly stimulated by P.T.H.

Phosphorus Metabolism Diet 900mg/day Phosphorus Metabolism Duodenum & SI Active Transport/ Passive Diffusion 3mg /Kg/day ECF Bone 3mg /Kg/day 90% PT Glomerular Filtrate 6oo mg./ day

BONES STRUCTURE

A. Matrix : Type-1 Collagen Fibers. (90-95%,give tensile strength.) COMPOSED OF : A. Organic matrix ( 30%) B. Deposits of calcium salts ( 70%) A. Matrix : Type-1 Collagen Fibers. (90-95%,give tensile strength.) Ground substance (5-10%) B : Salts : Made of ECF and Proteoglycans, (Chondroitin sulphate & hyaluronicacid) Salts –Mainly Calcium & Phosphate, (hydroxyapatite crystals ) also, Mg, Na, K, &.carbonate ions form bone salts. Uranium, Plutonium, Lead, Gold. Give compressional strength.

BONE CELLS

TYPES 1. OSTEOBLASTS- Found on outer surface and cavities,forms new bone & brings about Ca and PO4 exchange 2. OSTEOCYTES-a.Found within osteoid. b. Formed from osteoblasts. c. Responsible for Ca & PO4 exchange. 3. OSTEOCLASTS- Found near osteoblasts, reabsorb bone.

Hormones which increase osteoblast activity: Growth hormone Estrogen Growth factors Calcitonin Hormones which increase osteoclast activity: Parathyroid Hormone. Vit. D.in very high conc.

DEVELOPMENT OF BONE CELLS

BONE PHYSIOLOGY

BONE REMODELLING 1. Bone deposition and absorption occurs continuously. 2. Normally in adults, deposition and absorption are equal. 3. In youngs,deposition> absorption. 4. In olds,absorption > deposition.

ADVANTAGES OF BONE REMODELLING 1.It adjusts the bone strength and shape with the stress put on it. 2. Old matrix degenerates gradually and has to be replaced with a new one. This maintains it’s strength.

Bone formation Osteoblasts secrete collagen & ground substance Collagen monomers polymerize to form collagen fibers Resulting cartilage like material that precipitates calcium salts is called Osteoid Entrapped osteoblasts become quiescent osteocytes

Bone Growth

CALCIFICATION OF BONES 1. Ca.& Po4, do not precipitate elsewhere due to inhibition by ? Pyrophosphates. 2. In bones : PrecipitationofCa.&PO4,(?neutralization of Pyrophosphate) ( Some Amorphous, + Most to Hydroxyapatite crystals)

3. Amorphous part remains as such, which is readily exchangeable with E.C.F. Ca & PO4. 4. Abnormalities : Precipitation in, a.Arteriosclerosis. b.Degenerating tissues. c.Old blood clots.

Calcium exchange between E.C.F and Bones. 1. Occurs within 30 min. to 1 hr.of a change in Ca++ conc. in E.C.F. 2. Buffering occurs between amorphous Ca.&PO4 in bones on one side and ECF on the other.

MECHANISM 1. Osteocytes and Osteoblasts in bone are in contact with each other, through cell processes running in canaliculi. 2. Functionally they form one continuous membrane called Osteocytic Membrane system (OSM).

3. This separates three different fluid compartments, general ECF towards the capillary, ICF within cells and the bone fluid (B. F.) towards osteoid. 4. There is a Ca++ pump pr. in the membrane towards the ECF side, which pumps Ca from ICF to ECF.

5.O.M.S. is permeable to Ca. & PO4 on the bone fluid side.

Bone resorption Brought about by osteoclasts by : a. Secretion of proteolytic enzymes, which will dissolve collagen. b. Secrete acids, like lactic and citric, which dissolve minerals.

Osteoclast resorbing bone Integrins Bone resorbing compartment

Bone Diseases A. Osteopetrosis : Defective osteoclasts – unable to resorb bone. Steady increase in bone density, narrowing / distortion of foramina Compression of nerves. Hematologic abnormalities – crowding of bone marrow cavities.

Osteoporosis 1.Aetiology:relative excess of osteoclastic function. 2. Loss of bone matrix is marked. 3. Incidence of fracture increases in bones like distal forearm, vertebral body, hips. 4. Commonly seen in old age, post menopausal women, patients immobilized for any reason 5. Prevention: increase calcium intake,exercise. 6. Hormone Replacement Therapy (H.R.T.)

FRCTURE HEALING 1. Activation of Osteoblasts. 2. Conversion of Osteoprogenitor cells to Osteoblasts. 3. Formation of new bone called callus. 4. Increases due to mechanical pressure.