The flashcards below were created by user
on FreezingBlue Flashcards.
What are the 3 major forms of Vitamin D? (3)
Which one is most abundant in circulation? Which one is active form? Which one is from plants?
- 1. Vitamin D2 (ergocalciferol) - plants
- 2. Vitamin D3 - calcidiol and calcitriol(cholecalciferol) - animals
Calcidiol (25(OH)-D3) = most abundant form in body (1000x more than calcitriol) measured in clinical labs
Calcitriol (1,25(OH)-D3) = active hormonal form
What are the major functions of Vitamin D? (4)
1. Calcium/bone metabolism (affects intestinal absorption of Ca and P - mostly Ca & osteoblasts, affects PTH production, kidney).
2. Cell differentiation
3. Immunity/Infection - not sure but vit D receptors are all over body
4. Gene regulation - upregulates calbindins and downregulates PTH and FGF-23
Egg yok, cod liver oil (also high in vitamin A), mushrooms, deepsea fish, fortified milks and cereals
What is the range of intake? UL?
400 IU (babies) to 800 IU (elderly
2. What does it depend on? (3) Why?
3. How does it enter lymphatic system?
4. What is efficacy of absorption?
- 1. In duodenum and jejunum
- 2. Depends on pancreatic lipases, bile and micelles in gut - b/c it's fat-soluble
- 3. Via chylomicrons
- 4. ~50% - Vitamin C is 50% if taken over 1000 mg!
How is Vitamin D transported?
- What is it similar to?
How is vitamin D2 transported vs Vitamin D3? What else is carried by the same carrier protein? From where? (3)
1. With Vitamin D-binding protein (like vitamin A and retinol binding protein) - DBP
2. All forms of Vitamin D and its metabolites are transported by vitamin D binding protein. Picks up metabolites from skin, liver and kidney.
1. Where is DBP made?
2. Where is vitamin D stored & in what form?
3. What are serum vitamin D levels like for obese people?
- 1. Liver
- 2. Unlike vitamin A, not in liver, mostly in adipose tissue as calcidiol.
- 3. Lower, bc of extra storage in adipose tissue
What is mechanism for vitamin D biosynthesis? 5 steps
What regulates the renal step and how? (3)
What does increasing hydroxylation do?
What regulates 1-hydroxylase activity overall? 5 and how?
What do both steps need?
- 1. UVB rays trigger conversion 7-dehydrocholesterol--> cholecalciferol (aka provitamin D)
- 2. cholecalciferol is picked up by VDBP and carried to liver
- 3. Liver - 25-hydroxylase: 7-DHcholesterol --> 25 (OH)vitamin D (calcidiol) - unregulated step.
- 4. Calcidiol is released into plasma and binds to DBP as calcidiol and goes to kidney
- 5. Kidney - a1hydroxylase: calcidiol --> calcitriol. regulated step by PTH, Ca2+ and FGF-23.
- - PTH increases synthesis of a-1 hydroxylase (induced by low calcium) while FGF23 inhibits this enzyme.
Increases solubility of fat-soluble vitamin in aq soln (blood)
D3 levels, PTH, FGF23, levels of Ca2+ and phosphate (low levels activate vitamin D synthesis)
What are the two products of a1-hydroxylase?
1. Calcitriol - active hormonal forms that interacts with VDR to affect gene transcription
2. Inactive metabolite that is excreted through bile or urine
Describe mechanism of how vitamin D induces gene expression? (4)
What are its effects? (5)
- 1. Vitamin D is carried in blood, dissociates from VDBP and enters cell and nucleus.
- 2. In nucleus, vitamin D binds to vitamin D receptor (VDR; nuclear hormone receptor) forming activated complex
- 3. Activated complex dimerizes then acts as transcription factor
- 4. Binding to VDRE to promote genes involved in mineral metabolism, etc.
- 1. Small intestine - increases calbindins for Ca2+ absorption
- 2. Increases bone formation - stimulates bone osteoblasts to build matrix. At high D intake, osteoblasts signal osteoclasts to increase resorption w/ PTH.
3. Renal tubular cells - enhances Ca2+ and Pi reabsorption
4. Mucosal cell uptake of phosphorus - hormone enhances absorption from gut lumen.
5. Cell proliferation/differentiation/apoptosis
What are causes of deficiencies at source? (2)intestine? (1) Liver? (2)
Kidney (2) Target organs? (3)
- 1. No D in diet/no sunlight
- 2. Fat malabsorption
- 3. Liver: liver disease/drug effects
- 4. Kidney: renal disease, genetic defect in a1-hydroxylase
- 5. Genetic defects in receptor, poor hormone binding, unstable receptor
1. What is RDA of calcium?
2. What are the 6 major functions?
- 1. 1000 mg/day, but might be too high.
- 2. Calmodulin-mediated pathways (regulatory actions in cells), cell proliferation/cycle/differentiation/apoptosis 3. muscle contraction 4. neuronal function 5. Glandular secretion (hormone release, i.e, insulin). 6. Glycogen synthesis pathway
1. Where is calcium absorbed?
2. What is bioavailability/efficiency of absorption?
3. What is mechanism of calcium absorption? (2)
- 1. Duodenum & jejunum
- 2. Usually 15-30%, if low intake then ~50%
- 3.Transcellular vs. Paracellular
- (1) Transcellular - Active saturable process occurring in duodenum and upper jejunum, occurs when intakes are LOW and is stimulated by vitamin D (via VDR gene transcription), sets up calbindins
(2) Paracellular - passive, nonsaturable process throughout intestine that occurs when calcium intakes are high. Can "push" Ca across tight junctions, not efficient.
Describe transcellular transport vs. paracellular transport of calcium?
- Requires energy?
- Does it occur when calcium levels are low or high?
- Which depends on Vitamin D VDR/gene transcription?
- Which one activates calbindins?
- What enzyme is used at the end? How many Ca2+s can calbindin carry?
- (1) Transcellular - Active saturable process occurring in duodenum and
- upper jejunum, occurs when intakes are LOW and is stimulated by vitamin D
- (via VDR gene transcription), sets up calbindins(2)
- Paracellular - passive, nonsaturable process throughout intestine that
- occurs when calcium intakes are high. Can "push" Ca across tight
- junctions, not efficient.
- - Transcellular
- - Transcellular (low) paracellular (high)
- - Transcellular
- - Transcellular
Calcium ATPase. 4 Ca2+
How are calcium levels regulated?
1) Major hormones? (3)
2) Major organs? (3)
4) Phosphate's role?
- 1. PTH - increases plasma Ca2+ and decreases Pi. Acts on bones (bone resorption), kidney (reabsorption) and intestine (stimulates vitamin D synthesis resulting in increased Ca2+ absorption).
- 2. Vitamin D (increases Ca2+ absorption in intestine, renal tubules and Pi in kidneys)
- 3. FGF23 (decreases vitamin D and calcium intake)
- 2. Bone, kidney intestine
- 3. Calcium can deposit in arteries and heart valves resulting in calcification
- 4. High phosphate intakes reduce calcium excretion (PTH response decreases as serum Ca2+increases), increases FGF-23 which inhibits Vitamin D.
- 5. Sodium increases calcium excretion.
What hormones regulate calcium levels and how?
- 1. PTH - activates vitamin D, increases plasma Ca2+ and decreases Pi. Acts on bones (bone
- resorption), kidney (reabsorption) and intestine (stimulates vitamin D
- synthesis resulting in increased Ca2+ absorption).
2. Vitamin D (increases Ca2+ absorption in intestine, renal tubules and Pi in kidneys)
3. FGF23 (decreases vitamin D levels and calcium uptake)
Where does most reabsorption in kidney take place? Via which hormone? How is it measured?
- 1. Proximal tubule (~97%)
- 2. Mostly PTH though Vit D can play a role
- 3. 24 hour urinary collection
What stimulates vitamin D synthesis?
Increased PTH levels due to low serum calcium
What happens to the following when Ca2+ levels in blood are low and high?
2. Vitamin D
3. Intestinal absorption of Ca
4. Release of Ca and phosphate from bone
5. Renal excretion of Ca
6. Renal excretion of P?
7. General response?
What happens when calcium levels go down? --> --> splits off to four:
Produced by who? (2)
What happens when FGF-23 levels increase? (3)
What is an increase in FGF-23 levels a risk factor for?
- 1. Produced by osteoblasts and osteocytes (osteoblast covered in matrix its secreted)
- 2. When Pi levels are high usually due to high intake
- 3. (1) Suppression of bone matrix formation (2) Increased urinary P excretion (3) Inhibition of calcitriol production in kdiney
- 4. Hip fractures
How do FGF-23 and PTH affect Pi levels? Ca2+ levels/
- 1. Both increase excretion of Pi
- 2. FGF-23 inhibits vitamin D (decreases calcium uptake) whiel PTH increases vitamin D levels and calcium intake. Both decrease bone formation.
Where is P found? (2)
WHat happens when there's a low Ca:P ratio? (2)
- 1. Hydroxyapatite crystals in bone and fluoroapatite in teeth.
- 2. PTH in serum increases to correct for decrease in serum Ca --> bone resorption decrease in BMC and BMD
What is bone important for? (5)
What are clinical signs of vitamin D deficiency - lab? (4)
1. Mechanical support of body, protection of tissues, metabolic reservoir for calcium and site of formation of RBCs & white blood cells & site of bone precursor cells (OB, OC, fat/muscle cells)
- 1. Low serum Ca2+ and P
- 2. Elevated alkaline phosphatase bc of increased osteoblast activity for new matrix formation
- 3. Elevated PTH from low serum Ca2+
- 4. Bone changes - rickets in lower limbs, breastbones, birth canal bones. Rickets in children and osteomalacia in adults.
What are the two types of bone? What are the two types of phases?
- 1. compact vs. trabecular
- 2. inorganic/mineral phase (hydroxyapatite crystals) and organic phase (osteocalcin, cross-linked collagen fibers)
What are the two types of scores for bone density and what do they mean? What is bone density measurement called? What are normal, osteopenia and osteoporosis scores?
1. T score (vs. young normal - 30 y/o) and Z-score (vs. age-matched control - for younger kids and adults)
- 2. DXA
- 3. Normal >= 1, Osteopenia -1-2.5, Osteoporosis =< -2.5
Who is at risk for vit D def? (5)
- 1. Exclusively breastfed infants (esp darker skinned)
- 2. Adults > 50
- 3. Alcoholics
- 4. Milk allergies
- 5. Those living in North during winter/limited sun exposure
When can rickets not appear anymore? What is it called after that? What is rickets characterized by? What is it caused by? (3)
- 1. After closure of bone's epiphyseal growth plates
- 2. Osteomalacia
- 3. Soft matrix - impaired mineralization of growing bones
- 4. Vitamin D deficiency, receptor problem or calcium inadequacy
What are symptoms of osteomalacia (2)
When does it occur - what does it fail to do?
What is the characteristic symptom of osteomalacia? Are osteoblasts still functioning? Is matrix still being made?
Can you have osteomalacia and osteoporosis at the same time?
- 1. Bone pain and muscle weakness
- 2. After epiphyseal plates have closed - failure to mineralize matrix in bone
- 3. Increase in ratio of nonmineralized bone to mineralized bone
- 4. Yes, osteoblasts are still functioning and creating matrix, it's just not being mineralized.
What's the diff between osteomalacia and osteoporosis?
Why does osteoporosis occur? (2)
1. Osteomalacia broken down matrix = reformed matrix, but reformed matrix just isn't mineralized.
2. Osteoporosis broken down bone >> reformed matrix due to impaired vitamin D metabolism or low estrogen
What is osteoporosis characterized by? (2)
When would you see osteoporosis in young people?
What are causes? (4)
What are risk factors? (7)
What is estrogen's role?!??!?!?!?!
- 1. Low vitamin D levels and rapid loss of bone in first 5-7 years after menopause
- 2. Steroids
- 3. Insufficient bone mass accrued during peak growth period, poor diet, limited physical activity, high rates of bone turnover
- 4. Asian/caucasian, family history of osteoporosis, inadequate diet (inad calcium and vitamin esp early in life, elderly
5. Estrogen inhibits IL-6 release from osteoblasts. After menopause, no more estrogen, so IL-6 is free to signal to osteoclast to breakdown bone.
1. What is Vitamin D's largest target?
2. Does vitamin D play role in mineralization or mobilization of bone material?
3. What is the process of adult bone turnover? Child bone turnover?
4. What cells are active during resorption? Formation?
- 1. Bone
- 2. Both (demineralization with PTH)
- 3. Activation, resorption, formation. AFR.
- 4. Resorption (osteoclasts), formation (osteoblasts)
1. How does Vitamin D3 affect osteocalcin?
2. Do osteoblasts have VDR? What two things stimulate osteoblasts?
3. How does vitamin D activate resorption?
4. How do osteoblasts and osteoclasts interact?
- 1. INcreases osteocalcin activity (bone formation)
- 2. Yes, glucocorticoids and vitamin D
- 3. Signaling to osteoclasts
- 4. Osteoblasts secrete IL-6 telling osteoclasts to resorb bone
1. How is hyperacalcemia possible
2. HOw do calcium & vitamin D supplements help older adults?
3. What happens when you have vitamin D toxicity?
- 1. Supplements only
- 2. Not at all
- 3. Kidney damage, etc.
What are severe and insufficient amounts of intake of vitamin D? Normal? Toxicity? What occurs with each state?
- 1. Severe - <12.5 nmol; insufficient 50-100 nmol - rickets & osteomalacia
- 2. Normal : 400-800 IU/day - normal Ca2+ and P regulation, cell development, cell divisoin
- 3. Toxic (1250 mg/day (50,000 IU) - hypercalcemia, nausea and vomiting, excessive thirst, polyuria, severe itching, calcificatino of soft tissues