3. • Vitamin D is fat soluble
• Major function- Maintenance of normal
plasma level of calcium and phosphorous
• Major source(90%) – Endogenous synthesis in
skin by photochemical conversion of a
precursor , 7 dehydrocholesterol powered by
solar energy
• Adequate exposure to sunlight without
sunscreen before 10 am and after 3 pm at
least 15 min a day
4. • Remaining sources – deep sea fish , plants
,grains
• In plants vitamin D is present in a precursor
form , Ergosterol
• “Blacks have lower level of Vitamin D
production in skin because of melanin
pigmentation”
• (melanin pigmentation is protection against
UV induced cancer )
5.
6. METABOLISM
• 1.Absorption of Vitamin D along with other
fats in the gut or synthesis from precursor in
the skin
• Binding of plasma alpha 1 globulin (vit D
binding protein) & transport to liver
7. • Conversion into 25-Hydroxyvitamin D by
25-Hydroxylase in the liver
• Conversion of 25-OH-D to
1,25-dihydroxyvitaminD by alpha1 hydroxylase
8.
9. Renal production of 1,25-(OH)2-D is regulated
by
• 3 mechanism
• Hypocalcemia stimulates secretion of
parathyroid hormone ,which augments the
conversion of 25-(OH)-D to 1,25-(OH)2-D by
activating alpha1 hydroxylase
• Hypophosphatemia directly activates alpha1
hydroxylase
• In a feedback loop,increased level of 1,25-
(OH)2-D downregulate the synthesis of
metabolite
10. • I,25-(OH)2-D acts by binding to a high affinity
nuclear receptor that in turn binds to
regulatory DNA sequences, thereby inducing
transcription of specific target genes
• The receptors are present in most nucleated
cells of the body
11. • Vit D also appear to act through mechanism
that does not require transcription of target
genes
• This involves binding of 1,25-(OH)2-D to a
membrane associated vit d receptor(mVDR),
leading to activation of protein kinase C and
opening of Ca channels
12. FUNCTIONS
• Stimulates intestinal absorption of calcium
through upregulation of calcium transport,in
enterocytes
• Stimulates calcium resorption in renal distal
tubules
• Promotes the mineralization of bone
vit D is needed for mineralization of osteoid
matrix & epiphyseal cartilage.
• Interaction with PTH in the regulation of
blood Ca
13. Stimulation of intestinal Ca absorption
• Through the interaction of 1,25-(OH)2-D with
nuclear vit D receptor and the formation of a
complex with RXR
• The complex binds to Vit D response element
and activates the transcription of TRPV6,
which encodes a critical Ca transport channel
• TRPV6-a member of transient receptor
potential vanilloid family)
14. Stimulation of Ca reabsorption in kidney
• Vit D increases Ca influx in distal tubules of
kidney through the increased expression of
TRPV5
• TRPV5 expression is also regulated by PTH
15. Interaction with PTH
• Parathyroid glands have a Ca receptor that
senses even small changes in blood Ca
concentration
• Vit D and PTH enhance the expression of
RANKL (receptor activator of NF-kB ligand) on
osteoblasts
• RANKL binds to its receptor(RANK) located on
preosteoclasts –inducing differentiation into
osteoclasts.
16. • Through the secretion of HCL and activation of
proteases such as cathepsin K ,osteoclasts
dissolve bone and release Ca & P into
circulation
17. Mineralisation of bone
• Stimulates osteoblasts to synthesize Ca
binding protein osteocalcin involved in the
deposition of Ca during bone development
• Flat bones develop by intramembraneous
bone formation, in which mesenchymal cells
differentiate directly into osteoblasts ,which
synthesize collagenous osteoid matrix on
which Ca is deposited
18. • Long bones develop by endochondral
ossification ,through which growing cartilage
at the epiphyseal plates is mineralised and
progressively resorbed and replaced by
osteoid matrix that is mineralised to create
bone
19. • When hypocalcemia occurs due to Vit D
deficiency ,PTH production is increased
1.Activation of 1alpha hydroxylase
2.Increased resorption of Ca from bone by
osteoclasts
3.Decreased renal Ca excretion
4.Increased renal excretion of phosphate (increase
in FGF 23 ,one of a group of agents known as
phosphatonins that block phosphate absorption in
intestine and kidney)
• Normal serum Ca level is restored,
hypophosphatemia persists
20.
21. Normal level of 1,25-(OH)2-D 20-100ng/ml
DEFICIENCY STATES
Rickets in growing children
Osteomalacia in adults
• Result from diet deficient in Ca & Vit D or
limited exposure to sunlight
• Affect inhabitants of northern latitude
• Heavily veiled women
• Children born to mothers who have frequent
pregnancy followed by lactation
22. • Milder form of Vit D deficiency also called as
vitamin D insufficiency .leading to increase
risk of bone loss and hip fracture are common
in older adults in US and Europe
23.
24. RICKETS
• Overgrowth of epiphyseal cartilage due to
inadequate calcification & failure of cartilage cells
to mature
• Persistence of irregular masses of cartilage which
project into marrow cavity
• Deposition of osteoid matrix on inadequately
mineralised cartilaginous remnants
• Disruption of the orderly replacement of cartilage
by osteoid matrix, with enlargement and lateral
expansion of the osteochondral junction
25. • Abnormal overgrowth of capillaries and
fibroblasts in the disorganised zone resulting
from microfractures and stresses on the
inadequately mineralised ,poorly formed bone
• Deformation of the skeleton due to loss of
structural rigidity of the developing bones
26. • The gross structural changes in rickets depends on
the severity and duration of the process
• During the non ambulatory stage of infancy ,the
head and chest sustain the greatest stresses
• The softened occipital bones may become
flattened, & the parietal bones can be buckled
inwards by pressure
• With the release of pressure ,elastic recoil snaps
the bones back into their orginal position
(craniotabes)
• An excess of osteoid produces frontal bossing and
a squared appearance to the head
27. • Deformation of chest results from overgrowth
of cartilage at the costochondral junction
,producing the rachitic rosary
• The weakened metaphyseal areas of the ribs
are subject to the pull of respiratory muscles
and thus bends inwards ,creating anterior
protrusion of the sternum (pigeon breast
deformity)
• When an ambulating child develops rickets
,deformities are likely to affect the spine
,pelvis ,and tibia ,causing lumbar lordosis and
bowing of the legs.
28.
29.
30.
31. Osteomalacia
• The newly formed osteoid matrix laid down by
osteoblasts is inadequately mineralised ,thus
producing the excess of osteoid
• The contours of the bones are not affected ,the
bone is weak & vulnerable to gross fractures
,likely to affect vertebral bodies and femoral necks
• The unmineralized osteoid appears as a thickened
layer of matrix arranged about the more basoplilic
normally mineralized trabeculae
32. Vitamin D Toxicity
• Prolonged exposure to normal sunlight does not
produces an excess of vitamin D
• Megadoses of orally administered vit can lead to
hypervitaminosis
• Causes metastatic calcification of soft tissues
such as kidney
• In adult it causes bone pain and hypercalcemia
• In sufficiently large doses it is a potent
rodenticide
