Calcium in body(1100-1200gm)
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Plasma(1%);Bones
range : 9-
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(99%)
11mg/dL
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DiffusibleStable pool(99%) Readily (59%)
Non-diffusible
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(41%): bound
exchangeable
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to albuminpool(1%)
? Facts to keep in mind:-normal plasma level of
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calcium is 9-10.5mg/dl(5mEq/L,2.5mmol/L)
? Free, ionized calcium (Ca2+) is important for blood
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coagulation, muscle contraction and neuronalfunction
? Extent of calcium binding to plasma protein
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levels of plasma proteins
? What is the effects of acid-base disturbances
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on plasma protein-binding of Ca 2+ and theionized Ca 2+ concentration in blood?
Absorption of calcium in GIT
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? TRPV6 channels----> responsible for calciumabsorption in intestine
? Absorbed calcium sequestered by calbindin-D
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? Enters the blood stream via sodium calciumexchanger/ calcium dependent ATPase TRPV6
channels----> responsible for calcium absorption
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in intestine
? Absorbed calcium sequestered by calbindin-D
? Enters the blood stream via sodium calcium
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exchanger/ calcium dependent ATPase
Plasma calcium ?filtered by kidneys
98%-99% are reabsorbed (60% from PCT;
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remaining ?ascending loop of Henle and distal
tubule)
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PTH ---- regulates the re-absorption from distaltubule (regulates the expression of TRPV5
channels)
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PhosphorousTotal : 500-800 gm (plasma level = 2.5-4.5mg%)
80-85% : skeletal
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2/3rd :organic; 1/3rd inorganic (total plasma level = 12mg/dL)
kidney : 85%-90% of filtered Pi reabsorbed (PCT :active
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transport---sodium dependent Pi cotransport )Na- Pi IIa and Na- Pi IIc
Na-Pi II a ----> powerfully inhibited by PTH
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GIT : Pi absorbed in duodenum & other parts ofsmall intestine (Na-Pi IIb)
Excretion : ed : high phosphate diet,
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hyperparathyroidism
ed : low phosphate diet,
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hypoparathyroidismPhysiological effects of altered calcium levels:-
Hypocalcemia :-
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?ed neuronal excitability? tetany (calcium level about 6.4mg/dL)
? seizures
?Features of hypocalcemic tetany
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?Chvostek's sign
?Trousseau's sign
?carpopedal spasm
?laryngospasm
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Hypercalcemia (>12mg/dL)
?Depresses nervous system
?Sluggish reflex
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?Muscle activity depressed?Lack of appetite
?Constipation
List various functions of calcium and phosphate
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Physiology of Bone?Bone is a living tissue
?It is a specialized connective tissue
?Compact bone -30% matrix(framework)
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& 70% salts?Organic matrix :90-95% collagen fibers,mainly type1
&Groundsubstance (ECF+Proteoglycans).
?Bone salts:Hydroxypatites{Ca10(PO4)(OH)2}
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Compact /cortical bone Trabecular/Spongy bone?80%
?20%
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?Forms outer layer of bone. ?Inside the cortical bone?Surface to volume ratio low ?Surface to volume ratio high
?Nutrients provided by
?Nutrients diffuse from ECF
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Haversian canal.
Bone formation
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? During fetal development bone formationoccurs by:
Enchondral bone Intramembranous bone
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formation(majority) formation e.g.; clavicle,mandible, certain bones of
skull.
Bone formation by osteoblasts
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?Osteoid formation (95% collagen+5% proteoglycan) byosteoblasts.
?Osteoid is secreated towards the interior of bone.
?Precipitation of calcium and phosphate on surface of
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collagen (mineralization)
?Formation of hydroxyapatite , Ca10 (PO4)6(OH)2,
crystals (Ca:P:: 1.3-2)
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Magnesium, sodium, potassium, and carbonate ions are also
present among the bone salts
? Collagen :tensile strength;
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? hydroxypatite : compressional strength?Deposition and absorption of bone--remodeling of
bone
?Bone deposition and absorption are normally in
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equilibrium.
?Continual physical stress stimulates osteoblastic
deposition and calcification of bone.
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Bone Remodelling
Bone deposition & Bone resorption.
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Requires 3 types of cells.?Osteoblasts: secrete extracellular organic matrix
within which calcium phosphate crystal precipitate.
?Osteocyte: Retired osteoblast imprisoned within
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bony wall around them.
?Osteoclasts: Resorb bone by secreting acids &
enzymes.They are cells of mononuclear phygocytic
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system.
Mechanism of bone resorbtion
? Osteoclasts attaches to the part of bone
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to be reabsorbed by integrins .
Forms "sealing zone"
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? Proton pump(H+ dependent ATPases)migrateFrom endosomes to the cell membrane.
Ph to 4 in this zone
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Contd.? The acidic pH dissolves hydroxypatite,
And proteases breakdown collagen.
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Ca, P,and collagen breakdown products are
released into the interstitial fluid.
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?Hydroxyproline is an index of bone resorbtion.Factors controlling bone formationand
resorbtion
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? GH, IGF, insulin, estrogen, testosterone, vit D ,
calcitonin, PDGF, Stimulates bone
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formation.? Cortisol inhibits bone formation.
? Parathormone, cortisol,thyroxine,PGs,IL-1&6,
TNF, Stimulates bone resorbtion.
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?Despite supersaturation of calcium and phosphorus ions inECF hydroxypatite crystals fail to precipitate in other
tissues........... Why?
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?Osteoid? Osteocytes??Mechanism of bone absorption by osteoclasts?
?The importance of exchangeble calcium ion in bone?
Physiological importance of continued deposition and
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absorption of bone?
?Continual physical stress stimulates osteoblastic
deposition and calcification of bone....... How?
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?Factors that control bone formation and resorption?Applied physiology
? Osteoporosis : decrease in bone mass and
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density.? Involutional osteoporosis
?Postmenopausal osteoporosis
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? Causes:Hyperparathyroidism,Hyperthyroidism,
Cushing's syndrome ,vit c ,alcoholism,etc.
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? Treatment: Administeration of vit D andcalcium tablets.
Contd.
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Osteopetrosis? There is defective increase in bone formation.
? Rare & often severe disease.
? Osteoclasts are defective, unable to resorb
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bone in usual fashion so osteoblasts operateunopposed.
? Neurological and hematological abnormalities.
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