Vitamin D Flashcards
How is Vitamin D metabolized?
fat soluble vitamin so associated with lipids for digestion, absorption and transport.
* absorption associated with bile acids
* transported into circulation via CM
* taken up during hydrolysis of the CM
* Some may be stored in body lipids but most is taken to liver with the CM remnant
Biological functions of vitamin D
- Ca balance in blood
- regulator of bone mineral metabolism
- immunomodulator in the inflammatory pathway
- regulates cell growth having anti-proliferative effects
- reduces hypertension
What are the 2 main sources to make active vitamin D?
- 7-dehydrocholesterol in skin
- Vitamin D3 absorption by digestive tract
What is the pathway for making active vitamin D and its role in Ca & P metabolism?
concentrations in diet and skin dictate how much converts to 25-OH D3
Major role of active vitamin D
Helps maintain normal plasma Ca concentration
Role of active vitamin D in the intestine
↑ efficiency of intestinal Ca absorption
* from basal of 10-15% to 30-80%
* also ↑ P absorption
Role of active vitamin D in bones and kidney
Along with PTH it induces the formation and activation of osteoclasts & ↑ renal distal tubule reabsorption of Ca
How are most of the effects of active vitamin D induced?
Mainly mediated through alerations in gene expression
Differentiate between the structure of vitamin D:
* DHC
* Vitamin D3
* pre vitamin D
* active vitamin D
What is the skin form of vitamin D?
7 dehydroxycholesterol (DHC)
* steroid structure
What is the dietary form of vitamin D?
Vitamin D3
* no hydroxyl units
What is the pre vitamin D form?
25 (OH) D or calidiol
* 1 hydroxyl unit
What is the active vitamin D form?
1,25 (OH)2 D or calcitriol
* 2 hydroxyl units
What form of vitamin D is this?
Vitamin D3
What form of vitamin D is this?
pre vitamin D/ 25(OH)D/ calcidiol
What form of vitamin D is this?
active vitamin D/ 1,25(OH)2D/ calcitriol
Where is Vitamin D3 converted to calcidiol?
in the liver by 25-OH-ase enzyme (CYP2R1 gene)
Where is calcidiol converted to calcitriol?
In the kidney by 1𝝰-OH-ase enzyme (CYP27B1 gene)
How is vitamin D transported?
VDBP - vitamin D binding protein
What can increase gene expression for vitamin D activation in the kidney?
PTH can ↑ CYP27B1 gene expression
What is the negative feedback vitamin D3 synthesis & metabolism?
as plasma ↑ [1,25(OH)2D] the CYP27B1 & CYP24A1 gene expressions ↓
* (CYP27B also suppressed by FGF-23)
Toxicity of vitamin D in the skin
Impossible
* Vitamin D is photosensitive and degraded by increased exposure to sunlight
What is the best measure of vitamin D status?
serum 25(OH)D once liver has preformed it
* Biomarker of exposure
* Reflects vit D from cutaneous & food sources (& supplements)
* Long circulating half-life ~15 days
* However does not indicate amount stored
Draw the metabolism pathway for vitamin D
Sun exposure needed for adequate vitamin D intake?
Photobiology
* Adequate [25(OH)D] may be obtainable by 5-15 mins sun exposure, 10 AM to 3 PM, during summer
* Higher latitudes & during winter months, UVB photon path length too long for significant vitamin D synthesis
What factors effect efficiency of photobiology?
- lattitude
- geography
- skin colour
- ageing
- sunscreens
- clothing
- obesity
How does skin colour affect vitamin D synthesis from sunlight?
↑skin pigmentation ↓production of pre-vitamin D
* melanin blocks UVB
How does ageing affect vitamin D synthesis from sunlight?
↓ [7 DHC] in the epidermis & the capacity for the skin to produce vitamin D
How does sunscreens affect vitamin D synthesis from sunlight?
Diminishs the production of Vitamin D from the skin because sunscreens absorb UV radiation.
How does obesity affect vitamin D synthesis from sunlight?
Vitamin D is lipid soluble and with increased adipose tissue over time Vitamin D is stored & is less accessible and can build up to toxic levels
* sedentary may be associated with less sun exposure
What organs can impair the synthesis of active vitamin D with a disorder?
disorders affecting the parathhyroid, liver or kidney
What might be prescribed to patients with renal disease in terms of vitamin D?
oral supplements or intravenous injections of calcitriol are often prescribed
Draw the regulation of vitamin D
Draw summary of the synthesis and metabolism for Ca, P and vit D
What are the 2 forms of food sources of vitamin D?
It is rare to find naturally occurring active Vitamin D in foods.
* VITAMIN D2: found in plants
* VITAMIN D3: found in animals
vitamin D3 vs. vitamin D2
The biological activity of Vit D2 is 20-40% that of Vitamin D3
* Can add hydroxy molecules onto D2 by enzymes, so it plugs into same pathway but it is not as potent in helping to regulate Ca absorption and concentrations
natural sources of vitamin D
- Fatty fish (tuna, salmon, sardines, mackerel)
- Egg yolks
- Beef liver
- some Mushrooms
fortified food products of vitamin D
- Cow’s milk, yogourt, soy beverages
- OJ
- Ready to eat cereal
- Margarine
- infant formula
RDI values for vitamin D
Based on AIs because EARs were difficult to determine
* INFANTS: based on the average intake from breast fed and formula fed babies
* CHILDREN: based on children’s needs regardless of exposure to sunlight
* ADULTS: based on serum concentration of 25(OH)D
What groups are at risk for vitamin D inadequacy
- Breastfed infants – related to maternal intake
- Older adults
- People with limited sun exposure
- People with dark skin
- People with fat malabsorption
- People who are obese or have undergone bypass surgery – serum levels may rise temporarily with weight loss
Why is 1,25(OH)2D not a good indicator of vitD status?
- Short half-life ~15 hours, lots of degradation can occur
- Regulated by PTH, calcium & phosphate
- Does not decrease until deficiency is severe
toxicity of vitamin D from dietary intake
Can lead to a state of vitamin D “intoxication” or “hypervitaminosis D”
* Leads to hypercalcemia and eventually soft tissue calcification
* renal & cardiovascular damage
* usually if taking extremely high dose supplements over a long period of time
What is the optimal 25-OH-D serum concentrations?
80–120 nmol/L
or
30–60 ng/mL
Vitamin D status for deficiency, inadequacy, adequate and high levels
What is the associated disorder of vitamin D deficiency in children?
Rickets: If epiphyseal plates have not closed Vitamin D deficiency results in disorganization and hypertrophy of chondrocytes
* Softening of the bones
* Short stature
* Bone Deformities
What is the associated disorder with vitD deficiency in adults?
Osteomalacia: Poor mineralization of the collagen matrix
* Osteopenia: a decrease in the opacity of the skeleton
* Increased risk of skeletal fractures
* Bone pain
* decreased bone density
Causes and consequences of vitD deficiency
related to a number of diseases but unknown if it is association or causation
