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)

9%(Di.)

(0.2 mmol/L)

(Citrates,Po4)(Inactive)

50%

(1.2 mmol/L)

(Active form)

Non Diffusible

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%

absorbed.

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.)

GITract

Exchangable

20gms

Stable

980 gms

ECF

1000 mg

Glomerular Filtrate 10,000mg/ day

Diet(1000mg/day)

Feces

900 mg/day

Vitamin D+ Absorption

700mg/day

Secretion

600mg/day

Urine

100 mg/day

Calcitonin,+Vit.D

Resorption

(PTH,Vit.D +)

Bones

1,000gms

Calcium Metabolism

1000

+

600 mg

9900 mg PTH,Vit.D +(Cal- ),

300mg

• 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.

Distribution of BodyPhosphorus

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.

Duodenum& SI

3mg /Kg/day

BoneECF

Glomerular Filtrate

Diet

900mg/day

6oo mg./ day

Active Transport/ Passive Diffusion

3mg /Kg/day

90% PT

Phosphorus Metabolism

BONES

STRUCTURE

• 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

osteoclast

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.