vitamin-D

1. SIMS 305- Clinical Biochemistry
Dr. Ali Raza
Senior Lecturer
Centre for Human Genetics and Molecular Medicine (CHGMM),
Sindh Institute of Medical Sciences (SIMS), SIUT.

2. Vitamin D
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3. Dietary Sources of Vitamin-D
• Fish liver oil
• Egg-yolk
• Margarine
• Butter
• Cheese
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4. Vitamin D and Immunity
• Increases the activity of natural killer cells (cytotoxic lymphocytes).
• Increases the phagocytic ability of macrophages
• Reduces the risk of
• Virus-causing diseases (colds, flu).
• Cancers (Colon, reast and ovarian cancer).
• Cardiovascular disease
(Positive impact on the composition of plasma lipids)
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5. Vitamin D
• Need natural precursors of the vitamin D, called as ‘Provitamins’
• Only two Provitamins have been found in nature.
• Provitamin D2: Ergosterol, found in plants.
• Provitamin D3: 7-dehydrocholesterol, found in the skin.
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6. Transformation of inactive Provitamin to the active Vitamin-D
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7. Biologically Active Form of Vitamin D
• Calcitriol is the biologically active form of vitamin D
• Synthesized involve
liver : Synthesis of 25-OH-D3 in Liver (Calcidiol)
kidneys : Synthesis of 1, 25-di –OH-D3 (Calcitriol)
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8. Vitamin D
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9. Vitamin-D Regulation
Calcitriol synthesis is regulated by:
• Feedback inhibition of 1 α-hydroxylase
• Parathyroid hormone (PTH)
• Serum phosphate level
• Calcitriol regulates its own concentration since high levels of
calcitriol (1) Inhibit “1 α-hydroxylase” and
(2) Stimulates 24,25-di-OH-D3 (storage form)
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10. FUNCTIONS OF VITAMIN D
• Vitamin D is found to regulate calcium and phosphate
metabolisms by acting on
• Bones,
• kidneys,
• Intestinal mucosa
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11. FUNCTIONS OF VITAMIN D
Intestinal absorption of calcium and phosphate:
• Vit D binds to the chromatin of target tissue and
expresses the genes for Osteocalcin (Ca ++ binding
protein) & Ca++ ATPase in intestinal cells.
• This increases the Ca++ absorption by actively transporting
Ca++ across the plasma membrane against electrochemical
gradients.
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12. FUNCTIONS OF VITAMIN D
Mineralization of bones:
• Mineralization of bones is promoted by
1, 25, (OH)2D3
24,25(OH)2D3.
• Synthesis of Ca++-binding proteins (osteocalcin) and
alkaline phosphatase is promoted which increases calcium
and phosphate ions in the bone.
• These ions enhance the mineral deposition in the bone.
• 24, 25(OH)2D3 helps the deposition of hydroxyapatite in
bone. 12

13. Deficiency of Vitamin D—Clinical
Aspect
• Bow legs /knock knees:
Bending of long bones giving
rise to deformities.
• Hot-cross bun appearance of
head: fontanelles do not close
properly
• Pigeon breast appearance:
deformity of the chest
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14. Deficiency of Vitamin D—Clinical Aspect
Deficiency produces
(1) Rickets: Children
(2)Osteomalacia : Adults
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15. Types of vitamin D deficiency Rickets
(i) Type I:
Inherited autosomal recessive disorder
1-α-Hydroxylase deficiency
Defect in conversion of 25-OH-D3 to calcitriol
(ii) Type II :
Inherited autosomal recessive disorder
a single amino acid change in one of the zinc fingers of
the DNA binding sites for receptors.
makes the receptors non-functional.
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16. 2. Osteomalacia
Deficiency of vitamin D in adults is rare.
It can occur:
• In pregnancy and lactation
• In women who observe purdah
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17. 3. Renal Osteodystrophy
• When renal parenchyma is lost, it is unable to
form calcitriol and
calcium absorption is impaired.
• Hypocalcemia leads to increase in PTH which acts on bone to
increase Ca++.
• Results in excessive bone turnover and structural changes,
condition known as Renal osteodystrophy.
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18. Hypervitaminosis D
• Serious deleterious effects may be produced if large doses (500
to 1000 times) of vit D is taken for prolonged periods.
1. Immediate effects: Anorexia, thirst, constipation and polyuria.
Followed by nausea, vomiting and diarrhoea.
2. Delayed effects: Persistent hyper Calcaemia and phosphataemia
may produce
(a) Urinary lithiasis
(b) Metastatic calcification (deposition of calcium salts )
kidneys, bronchi, pulmonary alveoli, muscles, arteries and
gastric mucosa.
• Renal failure may develop and can lead to death. 18

19. CLINICAL ASPECTS
Recently low vitamin D level has been correlated with
certain diseases:
• Heart ailments
• Diabetes
• Breast cancer
• Peripheral artery disease
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20. Heart Ailments
• Low vitamin D levels (i.e. below 15 ng/ml) had double the
risk of developing heart problems
• Most organs and tissues of human body have vitamin D
receptors. E.g. smooth muscles of the heart and the blood
vessels.
• Causes these smooth muscles to relax and this in turn
prevents heart attacks/strokes.
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21. Diabetes: Vitamin-D in preventing diabetes.
• Vitamin D receptors are located in the β-cells of Islet of
Langerhans of pancreas.
• Association of Vitamin D and diabetes came from
population studies that insulin dependent Type-1 diabetes
occurred commonly in areas which receive less sunlight.
• Vitamin-D probably stimulates not only the release of
insulin but also the expression of insulin receptors.
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22. Breast Cancer
• Maintaining vitamin-D levels may actually prevent certain
types of cancers particularly breast cancer.
• Breast cancer cells have vitamin-D receptors, when these
receptors are activated with vitamin-D
• Vitamin-D brings some molecular reactions that can make
the cancer cells slow down their growth rate or quite
often even die or at least become less aggressive.
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23. Peripheral Artery Disease (PAD)
• Vitamin D may protect against an
PAD disease (fatty deposits restrict
blood flow to the limbs)
• Individuals with low levels of vit-D
experience an increase risk of PAD.
• Most often reduces blood flow to
the legs causing
pains,
numbness,
impairing the ability to work and
may lead to amputation. 23