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