Vitamin D is a fat-soluble vitamin that is important for intestinal absorption of calcium and phosphate. It can be synthesized in the skin upon exposure to sunlight or obtained from dietary sources. The liver and kidneys work to activate vitamin D into its functional form. Deficiency can lead to rickets in children and osteomalacia in adults, while toxicity in excess causes hypercalcemia and calcification of soft tissues.

1. VITAMIN D
Dr. Muhammad Sarfraz
M.B.B.S., M.Phil.(Pharmacology)
Senior Demonstrator
Quaid-e-Azam Medical College
Bahawalpur, Pakistan.
1

2. 2

3. Vitamin D
• Fat-soluble
Secosteroid ?
• Responsible For
Intestinal Absorption Of
Calcium And Phosphate.
3

4. Vitamin D
Also known as calciferol
1,25-dihydroxy vitamin D
(calcitriol)
vitamin D3 or
cholecalciferol
 vitamin D2 or
ergocalciferol 4

5. Vitamin D
• Once the vitamin enters the
body it must become
activated.
• Activation occurs through
the action of the liver and
the kidneys
5

6. Vitamin D
• Important Related Compounds
Of Vitamin D
• Vitamin D2
The plant version of
vitamin D
Ergocalciferol
(produced in fungi, mushrooms
and yeast by expposure of
ergosterol to UV rays)
6

7. Vitamin D
• Vitamin D3
Animal Version Of Vitamin D
• Cholecalciferol
Can Be Ingested From The
Diet And/Or Supplements
7

8. Cholecalciferol
8

9. Steroid Nucleus
9

10. Vitamin D
• Not Strictly a Vitamin
• Can Be Synthesized In The
Skin, And Under Most
Conditions That Is The
Major Source Of The
Vitamin
10

11. Vitamin D
• If Sunlight Exposure ...
Inadequate... Dietary
Source Required
11

12. Vitamin D
• Regulation Of Calcium
Absorption And
Homeostasis...
• Mediated By Way Of
Nuclear Receptors That
Regulate Gene
Expression 12

13. Vitamin D
Role In Regulating
Cell Proliferation
And
Differentiation
13

14. Function of vitamin D
Overall Function Of
1,25-Di(OH)- Cholecalciferol
Is To Maintain
Adequate Plasma
Levels Of Calcium
14

15. Function of vitamin D
Increasing uptake of
calcium by the intestine
minimizing loss of
calcium by the kidney
Stimulating resorption
of bone when necessary
15

16. Function of vitamin D
Effect Of Vitamin D On Bone:
1,25-Di(OH)- Cholecalciferol
Stimulates
The Mobilization
Of Calcium And Phosphate
From Bone
By A Process That
Requires
Protein Synthesis
And
The Presence Of PTH 16

17. Function of vitamin D
This Results In
Increase In
Plasma Calcium
And
Phosphate
17

18. Function of vitamin D
• Bone mineralization
1,25,di-OH-D3
24,25,di-OH-D3
Promote synthesis of
calcium binding proteins
Osteocalcin
Alkaline phosphatase
18

19. Function of vitamin D
• Effect of vitamin D on the intestine:
• stimulates intestinal
absorption of calcium and
phosphate.
• 1,25-diOH-D3 enters the
intestinal cell and binds to a
cytosolic receptor
19

20. Function of vitamin D
• 1,25-diOH-D3–receptor
complex then moves to the
nucleus
• it selectively interacts with
the cellular DNA.
20

21. Function of vitamin D
• As a result, calcium uptake is
enhanced by an increased
synthesis of a specific
calcium-binding protein.
21

22. 22

23. 23

24. 24

25. Daily requirements
• Vitamin D occurs naturally
in fish, liver, and egg yolk
• Milk
not a good source of the
vitamin
25

26. Daily requirements
• AI for vitamin D is 200 IU to age
50
• 400-600 IU after age 50.
• higher doses of 800 IU/day have
been shown to reduce the
incidence of osteoporotic fractures
• 5 µg cholecalciferol = 200 IU
26

27. Vitamin D
• Deficiency
Leading To
• Rickets In Children
And
• Osteomalacia In Adults
• Problem In Northern
Latitudes, Where Sunlight
Exposure Is Inadequate
27

28. 28

29. Vitamin D
Synthesized In The Skin
• 7-Dehydrocholesterol
•An Intermediate In
The Synthesis Of
Cholesterol That
Accumulates In The
Skin 29

30. 30

31. Vitamin D
Synthesized In The Skin
Nonenzymatic Reaction
on exposure to
ULTRAVIOLET-B LIGHT
(290-320 nm wavelength)
yielding
previtamin D3
31

32. Vitamin D
Synthesized In The Skin
• This undergoes a Further
Reaction over a period of
hours to form
“Cholecalciferol”
which is Absorbed Into The
Bloodstream
32

33. 33

34. Fig. 11-9, p. 377
1,25-dihydroxy Cholecalciferol
(active form) Stepped Art
In the liver:
Ultraviolet
light from the
sun
In the
kidneys:
Vitamin D3
(Cholecalciferol)
Hydroxylation
Foods
In the skin:
7-dehydrocholesterol
(a precursor made in the
liver from cholesterol)
Previtamin D3
25-hydroxy Cholecalciferol
Hydroxylation

35. 35
Although the kidneys produce most of the calcitriol that ends up in the blood, there is
some evidence that the conversion of 25(OH)D3 into 1,25(OH)2D3 may occur in other
tissues in the human body. The production of calcitriol in these tissues is low in
comparison to the kidney, and calcitriol made in these tissues is probably not released
back into the serum. This calcitriol acts within the tissue where it’s made:
Cells of the immune system (macrophages, dendritic cells)
Brain
Breast
Colon (large intestine)
Endothelial cells (inner lining of blood vessels)
Pancreas
Parathyroid glands
Placenta
Prostate
Skin

36. Vitamin D
Synthesized in the Skin
The Plasma
Concentration Of
Vitamin D Is
Highest At The End
Of Summer
Lowest At The End Of
Winter 36

37. Vitamin D status by blood levels of 25(OH)D*
Vitamin D status 25(OH)D in nanograms per
milliliter (ng/mL)
Deficient Less than 20 ng/mL
Insufficient 20 to 29 ng/mL
Sufficient 30 ng/mL or more
Potentially harmful More than 150 ng/mL
37

38. Vitamin D2
Ergocalciferol
(Made From Ergosterol)
38

39. Vitamin D3 .....
Cholecalciferol
(made from 7-dehydrocholesterol in the skin)
39

40. Vitamin D Synthesis
• Cholecalciferol, either
synthesized in the skin or
from food
• Two Hydroxylations to yield
the active metabolite
1,25-dihydroxyvitamin D
calcitriol 40

41. Vitamin D Synthesis
Ergocalciferol
from fortified foods
undergoes similar
hydroxylation to yield
Ergocalcitriol
41

42. Vitamin D Synthesis
In the liver, cholecalciferol is
hydroxylated by
25-Hydroxylase
to form the
25-hydroxy derivative
CALCIDIOL
42

43. CALCIDIOL
Released Into The
Circulation Bound To
Vitamin D Binding
Globulin
Main Storage Form
43

44. In the kidney
calcidiol undergoes
1-hydroxylation
Endoplasmic Reticulum
Proximal Covoluted Tubules
yield the active metabolite
1,25-dihydroxy-vitamin D
(CALCITRIOL)
44

45. Regulation of calcitriol synthesis
• Its own conc.
Feed back inhibition of
1 α-hydroxylase
Formation of 24,25-di-OH-D3
is stimulated
Less potent
ROLE IN BONE MINERALIZATION45

46. Regulation of calcitriol
synthesis
• PTH stimulates
• Low serum phosphate levels
• Hypocalcaemia by stimulating
PTH release
46

47. 47

48. 48

49. 49

50. Plants D2
• Ergocalciferol
• 25-Hydroxy
Ergocalciferol
• 1-25-Dihydroxy
Ergocalciferol
Animals D3
• Cholecalciferol
• 25-Hydroxy
Cholecalciferol
• 1-25-Dihydroxy
Cholecalciferol 50

51. Vitamin D
Roles in the Body
–Vitamin D in Other Roles
•Immune system
•Brain and nervous system
•Pancreas, skin, muscles,
cartilage, and reproductive
organs
51

52. FUNCTIONS OF VIT. D
• The MAIN FUNCTION of vitamin D is
in The Control Of Calcium
Homeostasis
Maintain
The
Plasma Calcium
Concentration 52

53. FUNCTIONS OF VIT. D
Calcitriol is involved in
Insulin Secretion
Synthesis and secretion of
Parathyroid
and
Thyroid
Hormones 53

54. FUNCTIONS OF VIT. D
Differentiation of
Monocyte
Precursor Cells
Modulation Of Cell
Proliferation
54

55. FUNCTIONS OF VIT. D
It Acts Like A Steroid
Hormone
binding to Nuclear
Receptors and Enhancing
Gene Expression
55

56. 56

57. • Vitamin D Deficiency
–Factors that contribute to
deficiency
•Dark skin
•Breastfeeding without
supplementation
•Lack of sunlight
•Use of nonfortified milk
57

58. RICKETS
•Insufficient exposure to
daylight and/or
• Deficiencies in vitamin D
consumption
58

59. Vitamin D Deficiency Affects Children
& Adults
RICKETS
• The Bones Of
Children Are
Undermineralized
Due To Poor
Absorption Of
Calcium 59

60. RICKETS
Continued Formation
Of The
Collagen Matrix
Of
Bone
But
Incomplete Mineralization
Resulting In
Soft, Pliable Bones
60

61. Osteomalacia
In Adults Results From The
Demineralization Of Bone,
Especially In Women Who Have
Little Exposure To Sunlight,
Especially After Several
Pregnancies 61

62. 62

63. 63

64. 64

65. Osteomalacia
65

66. Waddling gait
© 2008 Thomson - Wadsworth

67. © 2008 Thomson - Wadsworth

68. 68

69. Vitamin D
Deficiency
Rickets
© 2008 Thomson - Wadsworth

70. Vitamin D
Deficiency
–Growth retardation
–Mis-shapen bones
including bowing of the
legs
–Enlargement of the
ends of long bones
© 2008 Thomson - Wadsworth

71. Vitamin D
Deficiency
–Deformities of ribs
Rachitic Rosary Of
Rickets
–Delayed closing of
fontanel thus rapid
enlargement of the
head
© 2008 Thomson - Wadsworth

72. 72

73. Vitamin D
Deficiency
–Lax muscles
(resulting in a
protruding
abdomen) and
muscle spasms
© 2008 Thomson - Wadsworth

74. 74

75. 75

76. © 2008 Thomson - Wadsworth

77. 77

78. 78

79. 79

80. 80

81. Vitamin D Toxicity
81

82. Vitamin D Toxicity
More likely to be toxic
compared to other
vitamins
High-dose supplements
may cause toxicity
Exaggeration
Of Normal Functions
82

83. Vitamin D Is Toxic in Excess
Resulting In An
Hypercalcaemia
Polyurea
83

84. Vitamin D Is Toxic in Excess
This Can Lead To
High Blood Pressure
• Calcinosis
the Calcification Of Soft
Tissues.
• Renal stones
84

85. Vitamin D Is Toxic in Excess
Although Excess Dietary
Vitamin-D Is Toxic
Excessive
Exposure To Sunlight Does Not
Lead To
Vitamin D Poisoning
85

86. Vitamin D Is Toxic in Excess
• Because
Limited Capacity To
Form
7-Dehydrocholesterol
86

87. Vitamin D Is Toxic in Excess
Prolonged Exposure
Of Previtamin D To
Sunlight Leads To
Formation Of
Inactive Compounds
87