Calcium functions & metabolism Vitamin D functions & metabolism Calcium homeostasis Vitamin D Parathyroid Hormone (PTH) Calcitonin Hormone Rickets & Osteomalacia Hypocalcaemia & hypercalcaemia Osteoprosis

Bone is a specialized mineralized connective tissue containing:

1- Cellular ElementsCellular Elements: - Osteoblasts (bone forming cells) - Osteoclasts (bone resorpting cells)

2- Organic Matrix Organic Matrix - Proteins: Type I Collagen Proteoglycan - Inorganic Minerals: Calcium & Phosphate - Others: small amount of hydroxide and carbonate Calcium is tightly regulated with phosphorous in the bodyCalcium is tightly regulated with phosphorous in the body

Calcium is the most abundant mineral in the body: ~ 1 kg in a 70 kg man

~ 99% of the body’s calcium is present in the bone where it is combined with phosphate

Total Total CalciumCalcium

99 % 99 % in bonein bone

ICFICF

1 %1 %

Clotting Clotting

Excitability of Excitability of nerve & musclenerve & muscle

Bone formation Bone formation

Reservoir for Reservoir for ECF [Ca2+] ECF [Ca2+]

Metabolic Metabolic regulation for regulation for

action of action of hormones & hormones &

enzyme activationenzyme activation

ECFECF

ExcellentExcellent: Milk, milk products as cheese & yoghurt

Fair Fair Legumes, vegetables

Calcium in BloodCalcium in Blood

Plasma Plasma [Ca[Ca2+2+]]

is regulated by:is regulated by:

Parathyroid Hormone (PTH)Parathyroid Hormone (PTH)

Active Vitamin D (1,25 DHCC)Active Vitamin D (1,25 DHCC)

Calcitonin HormoneCalcitonin Hormone

A group of sterols with a hormone-like function.A group of sterols with a hormone-like function.

Sources of Vitamin DSources of Vitamin D

1- Skin synthesis (On Exposure to Sun Lights):1- Skin synthesis (On Exposure to Sun Lights): In the skin, 7 dehydrocholesterol 7 dehydrocholesterol is converted to vitamin D3 vitamin D3 by exposure to sunlight 2- Diet:2- Diet: - Animal Source Cholecalciferol (Vitamins D3)Vitamins D3) - Plant Source: Ergocalciferol (Vitamin D2)Vitamin D2) Vitamin 2 & D3 are NOTNOT biologically active

Activation of cholecalciferolActivation of cholecalciferol (vitamin D3)vitamin D3) CholecalciferolCholecalciferol (Vitamin D3) is activated in vivo to the biologically active form by two hydroxylations: first in the liverliver (at position 25) by 25 hydroxylase & then in the kidneykidney at positions 1 by 1 α hydroxylase

Active Vitamin DActive Vitamin D 1, 25 dihydroxycholecalciferol (Calcitriol )1, 25 dihydroxycholecalciferol (Calcitriol )

Vitamin DVitamin D22

plant sourceplant source

Vitamin D3Vitamin D3animal source

fatty fishLiver

egg yolk

7-dehydrocholesterol7-dehydrocholesterolIn the skin

DIET VITAMINs DDIET VITAMINs D

SOURCES OF VITAMIN DSOURCES OF VITAMIN D

Sun Sun RaysRays

Cholecalciferol (Vitamin D3) Cholecalciferol (Vitamin D3) is derived from 7-dehydrocholesterol in the skin by sunlight or supplied in the diet

In liver:In liver: Cholecalciferol is converted to 25-hydroxycholecalciferol25-hydroxycholecalciferol (25-HCC) by the enzyme 25 hydroxylase 25-hydroxycholecalciferol25-hydroxycholecalciferol is the predominant form of vitamin D in bloodblood 25-hydroxycholecalciferol 25-hydroxycholecalciferol is the main storagestorage form of vitamin in the body In kidneys:In kidneys: The 1 α hydroxylase enzyme converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol1,25-dihydroxycholecalciferol (1, 25 DHCC) which is biologicallybiologically active form of vitamin Dactive form of vitamin D

Active vitamin D (1, 25 DHCC) regulates calcium levels in the body (calcium homeostasis)Through:

Increasing absorption of calcium by the intestineIncreasing absorption of calcium by the intestine Minimizing loss of calcium by kidney Stimulating resorption of bone when necessary

Rickets & osteomalacia Rickets & osteomalacia are bone diseases occurring due to are bone diseases occurring due to

poor mineralization (calcium content) of bonepoor mineralization (calcium content) of bone

CausesCauses

II. Vitamin D deficiency. Vitamin D deficiency 1- Deficiency of sources of vitamin D3:1- Deficiency of sources of vitamin D3: BOTH:BOTH: Nutrional Vitamin D deficiency Nutrional Vitamin D deficiency Poor exposure to sun lightPoor exposure to sun light 2- Impaired vitamin D metabolism:2- Impaired vitamin D metabolism: Renal Rickets: deficiency of 1 hydroxylase of the kidneyRenal Rickets: deficiency of 1 hydroxylase of the kidney Deficiency of parathyroid hormone : decrease activity of 1 Deficiency of parathyroid hormone : decrease activity of 1 α hydroxylase hydroxylase

II. Calcium deficiencyII. Calcium deficiency

Vitamin D deficiencyVitamin D deficiency calcium of bone is mobilized outside bone

with demineralization of bone

Rickets OsteomalaciaRickets Osteomalacia

(in children) (in adults)

Renal RicketsRenal Rickets (Renal osteodystrophyRenal osteodystrophy)

Chronic Renal FailureChronic Renal Failure

Low activity of renal 1Low activity of renal 1hydroxylasehydroxylase

Decreased ability to form the Decreased ability to form the

active form of vitamin Dactive form of vitamin D(1, 25 DHCC)(1, 25 DHCC)

Treatment: 1,25 DHCC (Calcitriol)

RICKETSRICKETSNormal formation of the collagen matrix

BUTincomplete mineralization (poor calcification)

softsoft bones (like rubber)bones (like rubber)

Bone DeformityBone Deformity------------------------------------------------------------------------------------

OSTEOMALACIAOSTEOMALACIA

demineralization (poor calcification) of preexisting bones with

More Susceptibility toMore Susceptibility to FractureFracture

Blood levels of 25-hydroxycholecalciferol (25 HCC) Blood levels of 25-hydroxycholecalciferol (25 HCC) Blood calcium (hypocalcemia)Blood calcium (hypocalcemia) Blood Alkaline phosphataseBlood Alkaline phosphatase

PTH is the principal acute regulator of plasma [Ca2+]

The active hormone is secreted in response to al fall in plasma The active hormone is secreted in response to al fall in plasma Ca2+ resulting in in Ca2+ increase in blood. Ca2+ resulting in in Ca2+ increase in blood.

On bone:On bone: PTH stimulates bone resorption by osteoclasts resulting in release of

calcium ions from bones to blood in cases of hypocalcemia

On kidney:On kidney: 1- PTHPTH increases reabsorption of calciumcalcium from kidney tubules. 2- PTHPTH promotes activity of 1hydroxylase of the kidney (with more hydroxylation of 25 hydroxycholecalciferol (25 HCC) to 1,25 DHCC (activation of vitamin Dvitamin D) which increases intestinalintestinal absorption of calcium So, action of PTH on intestine is indirect (via Vitamin D) So, action of PTH on intestine is indirect (via Vitamin D)

Calcitonin hormone Calcitonin hormone :: secreted by the parafollicular or “C” cells of the thyroid gland Released in response to high blood calcium (hypercalcemia)

In cases of hypercalcemia,In cases of hypercalcemia,Calcitonin Hormone Calcitonin Hormone blood [Ca2+] by: blood [Ca2+] by:

Osteoclast activity Osteoclast activity (preventing release of calcium to blood)

Renal reabsorption of calciumRenal reabsorption of calcium Net result of its action Net result of its action blood calcium blood calcium CALCITONIN IS THE ONLY HYPOCALCEMIC HORMONECALCITONIN IS THE ONLY HYPOCALCEMIC HORMONE

Hypoparathyroidism (Hypoparathyroidism ( PTH) PTH) Vitamin D deficiency Vitamin D deficiency Renal disease (low 1 Renal disease (low 1 hydroxylase) hydroxylase) Hypoprotenemia (Hypoprotenemia ( Plasma Proteins) Plasma Proteins) Nutritional calcium deficiencyNutritional calcium deficiency

HyperparathyroidismHyperparathyroidism Malignant diseaseMalignant disease Drugs as lithiumDrugs as lithium ThyrotoxicosisThyrotoxicosis

Reduction in bone mass per unit volume Bone matrix composition is normal composition is normal but it is reducedreduced Post-menopausal women lose more bone mass than men

(primary osteoporosis)

Secondary osteoporosis may be caused by:Secondary osteoporosis may be caused by:Drugs ImmobilizationSmokingAlcoholCushing’s syndromeHyperthyroidism