Metabolism of Calcium , Phosphate , Vit D

DR. LAXMIKANTA DR. LAXMIKANTA SAYSAY

Metabolism of Calcium, Phosphate & Vit. D

Parathyroid gland

&Calcitonin

CALCIUM CALCIUM METABOLISMMETABOLISM

Distribution of Ca in Distribution of Ca in ECFECF

FUNCTIONS OF CALCIUMFUNCTIONS OF CALCIUM1. Calcium Homeostasis2. Promotes Neuromuscular

excitation-contraction coupling3. Blood Coagulation4. Membrane integrity & stabilization

of cell Membrane5. Release of Neurotransmitters from

synaptic vesicles6. Secretion from endocrine gland7. Synthesis of Nucleic acids &

proteins8. Activation of enzymes

Adult Man 800 mg/dayWomen, pregnant, lactation & post-menopause

1500 mg/day

Children (1-18Yrs) 800-1200 mg/day

Infants ( < 1Yr) 300-500 mg/day

Dietary requirements

Dietary SourcesMilk & Milk products

Beans, Leafy vegetables, Fish, Cabbage, Egg Yolk

CALCIUM BALANCECALCIUM BALANCE

PHOSPHOROUS PHOSPHOROUS METABOLISMMETABOLISM

FUNCTIONSFUNCTIONS1. Development of bone & teeth2. Structural Part of : i. High energy transfer - ATP, GTP ii. Co-factors – NAD, NADP, TPP iii. Second Messenger – cAMP, inositol

triphosphate iv. Nucleic acids (DNA & RNA)

3. Activation of enzymes by phosphorylation4. Role in Carbohydrate metabolism5.Phosphate buffer sysytem –pH regulation6.Balances intracellular anions

PHOSPHOROUS BALANCEPHOSPHOROUS BALANCE

Vitamin D Vitamin D

CHOLESTEROL CHOLECALCIFEROL

A

C D

B

SYNTHESISSYNTHESIS

REGULATION OF SECRETION OF Vit. REGULATION OF SECRETION OF Vit. DD

Other sites of Calcitriol Other sites of Calcitriol synthesissynthesis

Placenta Keratinocytes Macrophages

Mechanism of ActionMechanism of Action

ACTIONS OF Vit. DACTIONS OF Vit. D

Intestinal Ca absorptionIntestinal phosphate absorption

Renal excretion of Ca and phosphate

Action on bone

Applied AspectApplied Aspect

Rickets and OsteomalaciaVit. D resistance ricketsOsteoporosis

RicketsRicketsClinical FeaturesA. Bone defect1. Craniotabes2. Widening of wrist3. Collapse of Chest Wall4. Rickety Rosary5. Frontal bossing & posterior flattening

of skull6. Harrison’s Sulcus7. Bowing of Legs or Knock-knee8. Kyphosis & Pelvic deformities

B. General Features 1. Respiratory & G.I. infections 2. Developmental milestone Delay

C. Tetany & ConvulsionsD. Biochemical Changes Low plasma Calcium & PhosphateSerum alkaline phosphatase levels HighPlasma Calcitriol low & absentMangementVit. D 25-125 µgm (1000-5000 IU)/day 6-

8 wks

OsteomalaciaOsteomalaciaAmount of mineral accretion in bone per Amount of mineral accretion in bone per

unit of bone matrix is deficientunit of bone matrix is deficientFemalesFemales - Multiple pregnancies,

Lactation, Some time in Puberty

Clinical ManifestationClinical Manifestation i. Long bone - soft, painful, deformed &

terdernessii. Fractures occurs easilyiii. Proximal Myopathyiv. S.Ca2+ low, S. inorganic phosphate low,

S.alkaline phosphatase high

OsteoporosisOsteoporosis

Decrease in all constituents of Bone

Decrease in bone mass with preservation of normal ratio of mineral to matrix

Age >40yrs

Postmenopausal women

Parathyroid Parathyroid HormoneHormone

ANATOMYANATOMY

SYNTHESISSYNTHESIS

MECHANISM OF ACTION MECHANISM OF ACTION

Feedback MechanismFeedback Mechanism

ACTIONSACTIONS1. Effect on calcium & phosphate concentration in ECF

2. Absorption of calcium and phosphate from bone

3. Excretion of calcium and phosphate by kidney

4. Intestinal absorption of calcium and phosphate

5. Action on other ions

Applied Applied

HypoparathyroidismHyperparathyroidismPseudohypoparathyroidism

Hypoparathyroidism Hypoparathyroidism

Cause – ThyroidectomyChvostek′ s sign Trousseau′s sign

HYPERPARATHYROIDISMHYPERPARATHYROIDISM

PTHrPPTHrP140 aminoacidsEncoded by chromosome -12Site of synthesis – uterus , enamel ,

brain , Keratinocytes , smooth muscle

Action1.Growth and development of

cartilage in utero2.Transport of Ca in placenta3.Skeletal development4.Inhibit excitatory damage to

developing neuron

CALCITONINCALCITONINPolypeptide with 32 aminoacidSecreted from Clear cells (C – Cells) Clear cells (C – Cells)

or parafollicular cells of Thyroid gland

Also known as ThyrocalcitoninThyrocalcitonin

Normal Secretion is 0.5 mg/dayHalf Life 15 min.MW – 3000Normal Plasma Level – 0.2 ngm/ml

SECRETIONSECRETION

Stimulators1.Plasma Ca2.β- adrenergic agonist3.Dopamine4.Estrogen5.Gastrin6.CCK – PZ7.Glucagon8.Secretin

ACTIONACTIONBoneBone i. Inhibit osteoclastic activity ii. Inhibit active transport of Ca from bone to

ECFiii. Increase alkaline phosphatase synthesis

from osteoblast

KidneyKidney i. Synthesis of 1,25 DHCCii. Na+, Ca2+, Cl -, PO4 excretioniii. Excretion of Hydroxyproline derived from

bone

Cont.Cont.GITGIT i. Secretion of Water & Electrolyte ii. Gastric Motility & Acid secretionIii. Jejunal absorption of Ca2+ &Phosphate

Physiological significancePhysiological significance i. Active in Young individuals ii. Promote Ca2+ storageiii. Protection against Post prandial

hypercalcemiaiv. Protection of Mother during pregnancy

Calcium HomeostasisCalcium Homeostasis↓ Plasma Ca

↑ PTH secretion from parathyroid gland

↑ Plasma PTH

KIDNEY↑ Ca reabsorption ↑ 1,25 DHCC

Bone↑ Resorption

↓ Urinary excretion of Ca

↑ plasma 1, 25 DHCC

↑ Release of Ca into plasma

↑ Ca absorption in intestine

Restoration of plasma Ca towards normal

THANK YOUTHANK YOU