Ca HomeostasisCa Homeostasis

Dr. Ramadan Dr. Ramadan Mohamed Mohamed AhmedAhmed Eslam.anes@yahoo.comEslam.anes@yahoo.com

Bone StructureBone Structure

Bone cells:Bone cells:OsteoblastsOsteoblasts

Bone-building cells.Bone-building cells.Synthesize and secrete collagen fibers and other Synthesize and secrete collagen fibers and other

organic components of bone matrix. organic components of bone matrix.

OsteocytesOsteocytesMature bone cells.Mature bone cells.Osteoblasts that have become trapped by the secretion Osteoblasts that have become trapped by the secretion

of matrix.of matrix.Responsible for maintaining the bone tissue.Responsible for maintaining the bone tissue.

OsteoclastsOsteoclastsCells that digest bone matrix – this process is called

bone resorption

Bone Matrix & Crystals:Bone Matrix & Crystals:Formed mainly of collagen, proteoglycans esp.

chondroitin sulfate and hyaluronic acid And hydrxyappatite crystals (Ca + ph).

Mechanism of Bone Calcification Mechanism of Bone Calcification

The initial stage in bone production is the The initial stage in bone production is the secretion of secretion of collagen molecules collagen molecules and and ground substance ground substance (mainly proteoglycans)(mainly proteoglycans) by by osteoblastsosteoblasts. .

The collagenThe collagen monomers polymerize rapidly to monomers polymerize rapidly to form collagen fibers;form collagen fibers; the resultant tissue the resultant tissue becomes becomes osteoid. osteoid.

As the osteoid is formed, someAs the osteoid is formed, some of the of the osteoblasts become entrapped in the osteoidosteoblasts become entrapped in the osteoid and become quiescent. At this stage they are and become quiescent. At this stage they are called called osteocytes.osteocytes.

Mechanism of Bone Calcification Mechanism of Bone Calcification

Within a few days after the osteoid is formed, calcium Within a few days after the osteoid is formed, calcium salts begin to precipitate on the surfaces of the collagen salts begin to precipitate on the surfaces of the collagen fibers. fibers.

The precipitates first appear at intervals along each The precipitates first appear at intervals along each collagen fiber, forming minute nidi that rapidly multiply collagen fiber, forming minute nidi that rapidly multiply and grow over a period of days and weeks into the and grow over a period of days and weeks into the finished product, hydroxyapatite crystals.finished product, hydroxyapatite crystals.

The mechanism that causes calcium salts to be The mechanism that causes calcium salts to be deposited in osteoid is not fully understood. (The deposited in osteoid is not fully understood. (The osteoblasts supposedly also secrete a substance into the osteoblasts supposedly also secrete a substance into the osteoid to neutralize an inhibitor (believed to be osteoid to neutralize an inhibitor (believed to be pyrophosphate) that normally prevents hydroxyapatite pyrophosphate) that normally prevents hydroxyapatite crystallization. Once the pyrophosphate has been crystallization. Once the pyrophosphate has been neutralized, the natural affinity of the collagen fibers for neutralized, the natural affinity of the collagen fibers for calcium salts causes the precipitation.calcium salts causes the precipitation.

CALCIUM & PHOSPHORUSCALCIUM & PHOSPHORUS

Calcium : Calcium : The most abundant mineral in the bodyThe most abundant mineral in the body 99% of body’s calcium is present in bone 99% of body’s calcium is present in bone

together with phosphate as mineral together with phosphate as mineral hydroxyapatitehydroxyapatite

Phosphorus :Phosphorus : Important element in the human bodyImportant element in the human body 80% of phosphorus combine with calcium 80% of phosphorus combine with calcium

in bones & teethin bones & teeth Present in the form of organic Present in the form of organic

(phospholipids) & inorganic phosphate (phospholipids) & inorganic phosphate (mixture of HPO4- & H2PO4-)(mixture of HPO4- & H2PO4-)

Ratio of calcium to phosphorus 2:1Ratio of calcium to phosphorus 2:1

FUNCTION OF CALCIUMFUNCTION OF CALCIUM

Function of calcium:Function of calcium: Muscle contraction.Muscle contraction. Release of hormone.Release of hormone. Release of neurotransmitter.Release of neurotransmitter. Regulation of enzyme activity – activation of Regulation of enzyme activity – activation of

enzyme or binding proteins requires ca2+ as enzyme or binding proteins requires ca2+ as specific cofactorspecific cofactor

Cell division – involve in the process of Cell division – involve in the process of mitosis.mitosis.

Neuromuscular excitability.Neuromuscular excitability. Blood clotting.Blood clotting.

PLASMA CALCIUMPLASMA CALCIUM

Plasma calcium concentration in normal person Plasma calcium concentration in normal person approx approx 9-11 mg%.9-11 mg%.

3 forms:3 forms: Free or unbound or ionic calcium Free or unbound or ionic calcium

(Ca2+) – (Ca2+) – 50%50% Bound calcium – Bound calcium – 40%40% bound to bound to

albuminalbumin Complexed calcium – Complexed calcium – 10%10% is is

complexed with anions (HCO3-, complexed with anions (HCO3-, H2PO4), lactate & citrate.H2PO4), lactate & citrate.

All 3 forms are equilibrium with one All 3 forms are equilibrium with one another.another.

Bone and Its Relation to Extracellular Calcium and Phosphate

Hormonal regulation of Ca level

-PTH.- Calcitonin.- Vitamin D

ACTIONS OF PTH

++ plasma Ca and decreased plasma Ph

ACTIONS OF PTH ON TARGET ORGANS1. BONES OR SKELETON Calcium and Phosphate absorption from bones

a. Rapid Phase: ++ movement of labile Ca to ECF.b. Slow Phase: activation of osteoclasts

1. immediate activation of osteoclasts that are already formed2. formation of new osteoclasts.

2. INTESTINESEnhances both Ca and PO4 absorption from the intestines by increasing formation of 1, 25. dihydroxycholecalciferol (acive vit D).

3. KIDNEYS a. Increased renal tubular reabsorption of calcium in the distal tubules.b. decreased proximal tubular reabsorption of PO4.

Increased PTH release

Binds to osteoblast causing decreased

osteoblast activity and release of osteoclast-

stimulating factor

OSF causes increased osteoclast activity

Decreased bone deposition and increased bone

resorption

Increased calcitriol synthesis

Increased intestinal Ca2+ absorption

Decreased Ca2+ excretion

Increased Blood [Ca2+]

Decreased Blood [Ca2+]

1414

REGULATION OF PTHREGULATION OF PTH

LowLow serum serum [Ca][Ca] IncreasedIncreased PTH PTH secretion.secretion.

HighHigh serum serum [Ca] [Ca] DecreasedDecreased PTH secretion.PTH secretion.

HighHigh serum serum [ph] [ph] IncreasedIncreased PTH PTH secretion.secretion.

ActiveActive VitaminD VitaminD decreaseddecreased PTH PTH secretion. secretion.

CALCITONINCALCITONIN Secretion of calcitonin is stimulated by Secretion of calcitonin is stimulated by

increase in blood calciumincrease in blood calcium Inhibit calcium resorption from bone & Inhibit calcium resorption from bone &

increase bone calcification.increase bone calcification.Two ways:Two ways:

1. 1. decrease resorptive activities of the osteoclasts decrease resorptive activities of the osteoclasts – – immediate effectimmediate effect 2. 2. decrease formation of new osteoclasts decrease formation of new osteoclasts – – prolonged effectprolonged effect

Stimulate renal excretion of calcium & Stimulate renal excretion of calcium & phosphorus; thereby decrease blood phosphorus; thereby decrease blood calcium levelcalcium level

Involve in counteracting calcium Involve in counteracting calcium mobilization action of PTHmobilization action of PTH

Calcitonin Negative Feedback LoopCalcitonin Negative Feedback Loop

Increased Blood [Ca2+] Increased calcitonin release from thyroid C cells.

Increased osteoblast activity

Decreased osteoclast activity

VITAMIN DVITAMIN D

Steps that Lead to the Formation of Substances from Vitamin D

- Cholecalciferol (Vitamin D3) is Formed in the Skin- Cholecalciferol is Converted to 25 Hydroxycholecalciferol in the liver- Formation of 1,25-Dihydroxycholecalciferol in the Kidneys and Its Control by Parathyroid Hormone- Calcium Ion Concentration Controls the Formation of 1,25 Dihydrocholecalciferol

ROLE OF CATCITRIOLROLE OF CATCITRIOL Active form of vitamin DActive form of vitamin D Stimulates GI absorption of both calcium Stimulates GI absorption of both calcium

and phosphateand phosphate Stimulates renal reabsorption of both Stimulates renal reabsorption of both

calcium and phosphatecalcium and phosphate Stimulates osteoclasts in case of Stimulates osteoclasts in case of

decreased plasma Ca.decreased plasma Ca. Stimulates osteoblasts in case of Stimulates osteoblasts in case of

increased plasma Ca.increased plasma Ca.

Net effect of calcitriol Net effect of calcitriol ↑ ↑ serum calciumserum calcium↑ ↑ serum phosphateserum phosphate

HypoparathryroidismTetany

Increased neuromuscular excitability due to decreased Ca level in the blood.

Types of tetany: 1.Manifest tetany: plasma Ca level below 7mg%, complicated by laryngeal spasm and may be death.

2. Latent tetany: plasma Ca between 7-9mg%.Manifestations not appear during rest, may be during stress. Diagnosed by

Hypocalcemic tetany in the hand, called carpopedal spasm

Clinical signs of hypocalcemiaClinical signs of hypocalcemiaCHVOSTEK’S SIGNCHVOSTEK’S SIGN Elicitation: Elicitation: Tapping on the face at a point just anterior to the Tapping on the face at a point just anterior to the

ear .ear . Postitive Postitive responseresponse: : Twitching of the ipsilateral facial muscles, Twitching of the ipsilateral facial muscles,

suggestive of suggestive of neuromuscular excitability caused by neuromuscular excitability caused by hypocalcemiahypocalcemia

TROUSSEAU’S SIGNTROUSSEAU’S SIGN Elicitation: Elicitation: Inflating a sphygmomanometer cuff above systolic Inflating a sphygmomanometer cuff above systolic

blood pressure for several minutesblood pressure for several minutes Postitive response: Postitive response: Muscular contraction including flexion of Muscular contraction including flexion of

the wrist and meta carpophalangeal jointsthe wrist and meta carpophalangeal joints

REGULATION OF PLASMA REGULATION OF PLASMA CALCIUM LEVELCALCIUM LEVEL

Homeostasis of plasma calcium is Homeostasis of plasma calcium is depend on 3 main organs (bone, kidney depend on 3 main organs (bone, kidney & intestine) & 3 main hormones (PTH, & intestine) & 3 main hormones (PTH, Vit D & Calcitonin)Vit D & Calcitonin)

3 major process to maintain plasma 3 major process to maintain plasma calcium levelscalcium levels Absorption of calcium from intestine through Absorption of calcium from intestine through

action of Vit Daction of Vit D Reabsorption of calcium from kidney Reabsorption of calcium from kidney

through action of PTH & vit Dthrough action of PTH & vit D Dimeneralization of bone through action of Dimeneralization of bone through action of

PTH but facilitated by Vit DPTH but facilitated by Vit D

Other Hormonal Effects on BoneOther Hormonal Effects on Bone

Growth hormoneGrowth hormone, produced by the , produced by the pituitary gland, and pituitary gland, and thyroxine, thyroxine, produced produced by the thyroid gland, stimulate bone by the thyroid gland, stimulate bone growth.growth.

GH stimulates GH stimulates protein synthesis and cell protein synthesis and cell growth growth throughout the body.throughout the body.

Thyroxine stimulates Thyroxine stimulates cell metabolism and cell metabolism and increases the rate of osteoblast activityincreases the rate of osteoblast activity. .

In proper balance, these hormones maintain In proper balance, these hormones maintain normal activity of the epiphyseal plate until normal activity of the epiphyseal plate until roughly the time of puberty.roughly the time of puberty.

REFERENCESREFERENCESTextbook of medical physiology tenth Textbook of medical physiology tenth

editionedition

GUYTON & HALLGUYTON & HALL

Clinical Oral Physiology –Timothy s Clinical Oral Physiology –Timothy s miles,miles,

Concise medical physiology- ChaudhuriConcise medical physiology- Chaudhuri

Principles & Practice of medicine –Principles & Practice of medicine –Davidson ,6Davidson ,6thth edition edition