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VITAMIN-D

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OUTLINE

Chemistry Synthesis Metabolism

Functions Sources RDA

Deficiency Toxicity

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Vitamin - D

• Fat soluble vitamin.• sunshine vitamin.• Structure is like Sterol.• Act as Hormone• Synthesized in skin • Regulate Calcium & Phosphorus metabolism

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Chemistry

• It is available in 2 forms D3 – Cholecalciferol - Animal D2 - Ergocalciferol- Plant• Both are provitamins • Active form : Calcitriol

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Synthesis

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METABOLISM

Forms

D2

D3

Site

Duodenum &

Jejunum

Mechanism

Along with lipids

Requires bile salts

Absorption

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In Liver

• Transport : From skin & intestine to liver with DBP transport protein.

• Hydroxylation: At 25th by Hepatic 25-hydroxylase

• Microsomal monooxygenase requires cytochrome P-450, NADPH and molecular oxygen.

• Storage form: 25(OH)D3

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Activation

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In Kidney

• Transport : From liver with DBP transport protein.

• Hydroxylation: At 1st by 1 α-hydroxylase • Mitochondrial monooxygenase requires

cytochrome P-450, NADPH and molecular oxygen.

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Regulation of synthesis

Ca+2

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Functions

Major : • Calcitriol regulate plasma calcium and Phosphorus

level• Development of Bones & Teeth

Other :• Cell Differentiation & inhibit cell proliferation• Immunity

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Regulation of Calcium & phosphate

Action of Calcitriol on intestine

Action of Calcitriol on bone

Action of Calcitriol on kidney

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Action of calcitriol on the intestine

• Increases the intestinal absorption of calcium and phosphate

• By increased synthesis of calcium binding proteins calbindins & osteocalcin

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Calcitriol acts like a steroid hormone.• mechanism of action resmble to group –II hormones• It enters the target cell and binds to a cytoplasmic receptor.• The hormone receptor complex interacts with DNA and consequent transcription of specific genes that code for Calbindin

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Action of calcitriol on the bone

• Both bone mineralization & bone resorption• Mineralization of bone by increased

ostroblast activity • Mobilization of calcium from bone and

increased plasma calcium and phosphate level

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Action of calcitriol on the kidney

• Increased reabsorption of calcium and phosphorus in the DCT

• Decreased excretion of calcium and phosphorus

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sources

• Sunlight• Fish• Liver oil• Eggs• Milk & milk products • Fortified cereals

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Daily requirment Men and women- 200 IU(05µg/day)

Pregnancy and lactation – 400 IU(10µg/day)

Infants & Children – 400 IU(10µg/day) 1microgram of vitamin D = 40 IU

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Deficiency

• Inadequate supply – insufficient exposure to sunlight in persons who are bedridden for long time & cover their entire body, strict vegetarians

• Impaired absorption- obstructive jaundice

• Impaired production of 25hydroxy vitamin D3 - liver disease

• Impaired production of 1, 25 dihydroxy vitamin D3 – kidney disease

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• Medications:1. Phenobarbital and Phenytoin (used in

epileptic patients) can induce hepatic p450 enzymes to accelerate the catabolism of vitamin D

2. Corticosteroids: convert vit-D into inactive metabolites.

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Deficiency RICKETS(twist) Childrens

OSTEOMALACIA(bone softness) Adults

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Rickets

• Rickets is defective mineralization or calcification of bones resulting in soft, pliable bone deformities

• Age between 6 months to 2 years

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Signs and symptoms of rickets

Weight bearing bones are bent causing• Bow legs• Knock-knees• Rickety rosary• Pigeon chest

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Rachitic rosaryg (rachitic rosary

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Osteomalacia

• Softening of bone due to failure of mineralization

• Demineralization occurs mainly in spine, pelvis and lower extremities

• pain in ribs, spine, pelvis, and legs• Increased softness & susceptibility to fracture• Bowing of long bones• Difficulty walking, often with waddling gait

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Other conditions

• Renal rickets: in CRF active form of Vit-D is deficient

• Vitamin D resistance rickets: defect in receptors

• Renal osteodystrophy: CRF 1,25DHCC Ca+2 PTH Bone resorption & changes in bone tissue

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Toxicity • Toxic when Intake >2000IU/L for prolong period

Symptoms:• Hyper calcemia • Deposition of calcium in soft tissue like kidney, arteries• Kidney stone • Excessive intake leads to nausea, vomiting, loss of appetite

excessive thirst and weakness

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Answer the following • Vitamin D consider as Hormone?• Active form?• Storage form?• Organ involved in synthesis of Vit –D?• Synthesis regulated by?• Target organs of Vit- D?• Enzyme elevated in rickets??• Effect of calcium & phosphate on Vit-D

synthesis?

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Case:1

• A 10 year old boy with epilepsy had born deformities such as bow legs, knock knee, pigeon chest and delayed eruption of teeth. Laboratory findings indicate elevated plasma level of ALP. Interpret this case??

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Case:2

• A 40-year old man who presented with excessive thirst, frequent urination, muscle aches, nausea, vomiting, elevated calcium (13.5mg/dl), phosphate (7mg/dl)He reported taking Power Meal” for a month, which mistakenly contained 10,000 IU of vitamin D per serving. Interpret this case

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Thank you