Vitamin D Flashcards
Symptoms of rickets in infants and children?
Bones become soft and pliable due to inadequate mineralization; epiphysial cartilage continues to grow and enlarge without replacement of bone matrix and minerals
Bowed legs, enlarged knee joints
Crainotabes (soft spots in the skull)
Delayed closing of fontanelles
Delayed formation of teeth
Architect rosary
Poorly formed pelvis
Deformation of long bones are permanent
Vitamin d deficiency in infants and children?
Rickets
Vitamin D deficiency in adults
Osteomalacia
Symptoms of osteomalacia
Minerals are removed from bone - bones become soft and brittle, distorted
Constant rheumatic type pain; waddling gait
Causes of vitamin d deficiency
Low dietary intake of calcium and or vitamin d and a lack of exposure to sunlight
Who is susceptible to vitamin d deficiency?
Mainly occurs in the elderly in US and Europe
Infants
People with parathyroid, liver and or kidney diseases
Causes of vitamin D toxicity
Dietary ingestion of large amounts of vitamin d (most likely of all vitamins to cause reaction)
Exposure to sunlight poses no risk of toxicity
Symptoms of mild vitamin D toxicity
Anorexia Excessive thirst Nausea/vomiting Constipation Failure to grow
Symptoms of severe vitamin D toxicity
Calcification of soft tissues such as heart, kidneys, lung, pancreas Mental retardation Uremia Death from heart failure Fetal damage from high maternal intake
Sources of dietary vitamin d
Animal foods- liver, beef, veal, eggs, saltwater fish
Dairy and orange juice are fortified
Non dietary source of vitamin D
7 - dehydrocholesterol is synthesized in skin
- allows for absorption of specific wave lengths of light
- exposure to sunlight converts it to previtamin D3
Vitamin D is found in diet as?
Cholecalciferol (D3)
Ergocalciferol (D2) in plants
Absorption of vitamin d
Dietary vitamin d3 (cholecalciferol) is absorbed from micelles and transported to the liver
Transport of vitamin D
Vitamin d binding protein - is synthesized in the liver
Binds all forms of vit d and transports 60% to liver and extra hepatic tissues
Bound to calcidiol (25-OH-VD3)
What is the precursor to active Vit D3
25-OH-VD3 (calcidiol)
Vitamin D hydroxylation
Cholecalciferol in the liver is meTabolized by calciferol hydroxylase to generate inactive Vit d calcidiol (25-OH-VD3) - precursor to active vD3 calcitriol
Step 1 of Vit D hydroxylation
Calciferol hydroxylase (a mitochondrial enzyme, cytochrome p50 hydroxylase, NAPDH dependent)
Hydroxylates cholecalciferol at carbon 25
Efficient during low Vit D intake
Step 2 of vitamin D hydroxylation
25-OH-VD3 (calcidiol) that is bound to DBP in the blood is taken up by the kidneys
25-hydroxy vitamin D 1-a-hydroxylase (NADPH dependent mitochondrial enzyme)
hydroxylyzes it to 1,25-(OH)2VD3 (calcitriol) - active form
Regulation of 25-hydroxy vitamin D 1-a-hydroxylase
Hydroxylates calcidol to calcitriol
High levels of calcitriol and phosphorus inhibit it, low levels enhance it
Alternative inhibition of calcitriol
24-hydroxylase convertes (25-OH-VD3) (calciferol) to 24,25-(OH)2VD3
When calcitriol is high it is enhanced
Active form of Vit D3
1,25-(OH)2VD3 (calcitriol) - active form
Genomic actions of Vit D3
Analogous to Vit A
Stimulates differentiation of hematopoietic cells and intestinal cells
Osteoblasts to produce osteoclast differentiation factors
Reduces cell proliferation (fibroblasts, keratinocytes and lymphocytes
Cancer cell
Treatment of skin disorders
Bone disease, hyperparathyroidism
Non genomic actions of Vit D
Signal transduction pathways linked to cell membrane Vit D receptors
Binding of calcitriol to VDR causes:
1. Phosphorylation/dephosphorylation of enzymes
- Activation of 2nd messengers - protein kinase C, cAMP, phospholipase c, arachidonic acid, diacylglycerol, insositol phosphate
Results in opening of Gated Ca channels and increased Ca uptake by intestine osteoblasts and muscle cells
2nd messengers activated by active Vit D3
protein kinase C, cAMP, phospholipase c, arachidonic acid, diacylglycerol, insositol phosphate
Results in opening of Gated Ca channels and increased Ca uptake by intestine osteoblasts and muscle cells
Vitamin D role in calcium homeostasis
Calcitriol acts with PTH to maintain blood calcium levels
-Synthesis is stimulated in response in changes in blood calcium
What happens in response to hypocalcemia
Secretion of PTH is stimulated
PTH stimulated the 1-a-hydroxylase in the kidney
The synthesis of calcitriol is secreted
Calcitriol acts on target tissues to increase serum calcium levels (small intestine, bone and kidneys)
Main targets of calcitriol
small intestine, bone and kidneys
Effects of calcitriol on the kidney
increases expression of calbindin28 to increase renal calcium reabsorption
Effects of calcitriol on the bone
Stimulates osteoclast activity to direct the mobilization of Ca and P from bone and help maintain normal Ca levels
Effects of calcitriol on the intestine
Increase the absorption of Ca & P
It functions through cell surface and nuclear receptors
What is calbindin28
increases the renal calcium reabsorption
Genomic effects of calcitriol on the intestine
Binds to the VDR which increases the transcription of callbindin9
Increases the absorption and transport of Ca
Non-genomic effects of calcitriol on the intestine
Indices changes in brush border composition and topology to increase absorption
