Upload
gregory-sparks
View
228
Download
5
Embed Size (px)
Citation preview
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.