Download MBBS Calcium and Phosphate Lecture PPT

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Plasma(1%);

Bones

range : 9-

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(99%)

11mg/dL

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Diffusible

Stable pool(99%) Readily (59%)

Non-diffusible

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(41%): bound

exchangeable

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to albumin

pool(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 neuronal

function

? 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 the

ionized Ca 2+ concentration in blood?
Absorption of calcium in GIT

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? TRPV6 channels----> responsible for calcium

absorption in intestine

? Absorbed calcium sequestered by calbindin-D

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? Enters the blood stream via sodium calcium

exchanger/ 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 distal

tubule (regulates the expression of TRPV5

channels)

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Phosphorous

Total : 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 of

small intestine (Na-Pi IIb)

Excretion : ed : high phosphate diet,

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hyperparathyroidism

ed : low phosphate diet,

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hypoparathyroidism
Physiological 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 formation

occurs 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) by

osteoblasts.
?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)migrate

From 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 in

ECF 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 and

calcium 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 operate

unopposed.

? Neurological and hematological abnormalities.

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