Vitamin D, Calcium, Phosphorous
what is normal T score?
-1 SD or >
what is the T score for osteopenia?
-1 to -2.5
what is the T score for osteoporosis?
-2.5 or <
what are some things that affect phosphorous homeostasis?
1) decrease in stomach acidity by proton pump inhibitors 2) aluminum containing antacids 3) high does of 1,25-dihydroxyvitamin D 4) potassium supplements with phosphorous supplements 5) hormone replacement therapy increases phosphorous excretion
cellular action of calcium ions overview
1) regulatory actions in cells through calmodulin mediated pathways 2) cell cycle and proliferation 3) cell differentiation and apoptosis 4) muscle contraction 5) neuronal function 6) glandular secretion: hormone release 7) glycogen synthesis pathway
what is the active form of Vitamin D?
1,25 dihydroxyvitamin D3 (calcitriol)
how do they measure renal reabsorption of calcium?
24 hour urinary calcium
how to diagnose hypophosphatemia?
24 hour urine phosphate excretion
what enzyme is responsible for the second hydroxylation?
25-OH-vitamin D 1 hydroxylase
what is the normal phosphate serum level in adults?
3.59 +/- 0.40 mg/dl
efficacy of absorption of Vitamin D?
50%
effieciency of phosphorous absorption?
55-80% in adults and 65-90% in infants
what is vitamin D3?
7 dehydrocholesterol aka cholecalciferol or pro vitamin D
where is a majority of phosphorous found?
85% in the bone/teeth and 15% in the bone and soft tissues
where does a bulk of reabsorption happen?
97% in the distal tubular
is calcium deficiency common? and what is the threshold?
<400 mg/day - rare cand causes rickets
Persons at risk for Vitamin D deficiency?
EBF infants, adults >50 years, people with limited sun exposure or milk allergies, strict vegetarians, fat malabsorptive disorders, alcoholics, impairments in activation of vitamin D, defects in VDR signaling, diseases of GI, liver, kidney, impaired parathyroid,
where is vitamin D stored?
Fat cells, NOT liver
Dietary sources of Vitamin D
Fish, fish liver oil, egg yolk, etc.
what does VDR dimerize with?
RXR
what helps as an adaptational hormone to low Ca intake?
Vitamin D
how is Vitamin D transported in the plasma?
Vitamin D binding protein (DBP)
vitamin D function can be affected by other mineral deficiencies...
Zinc (indirectly affects renal 25OHD3 1 hyrdroxylase activity iron: impairs absorption of vitamin D boron: increase bone mobilization in vitamin d deficiency
steps to a dynamic process of adult bone turnover?
activation, resorption through osteoclasts, formation through osteoblasts
what is transcellular absorbtion?
active saturable process happens in duodenum and upper jejunum happens when there is low Ca intake
when does osteomalacia happen?
after ephiphyseal closure in older children and adults
how does vitamin D act?
as a steroid hormones.
how is phosphorous found in teh bone?
as hydroxyapatite crystals - calcium phosphate
rickets
associated with vitamin D deficiency. first appears in 6-24 month children (can manifest at any time until the closure of the bone's epiphyseal growth plates) impaired mineralization of the growing bones caused by lack of sunlight and insufficient calcium
what is the largest target organ for vitamin d?
bone - accumulates more than 1/4 of a single dose of the vitamin within a few hours
What are 3 organs involved in calcium homeostasis?
bone, kidney, intestine
what is the major circulating form of vitamin D?
calcidol
What are some factors that limit the biosynthesis of vitamin D?
clothing, lack of sunlight, latitude, season, time of day, sun screen, altitide
food choices with calcium?
dairy foods (yogurt), small bony fishes, almonds, tofu, dark greens, legumes
what are the effects of hypophosphatemia?
decreased bone mineralization, less mycardial contractility, muscle weakness, and increased affinity of Hb for O2,
treatment for hypophosphatemia?
depends on serum phosphate levels and symptomatic/asymptomatic manifestations either oral or IV phosphate repletion
whats the primary role of phosphorus?
determining how the body uses carbohydrates and fat
how is vitamin D and calcium involved?
drives mainly transcellular absorbtion when Calcium intake is low 1) increase calbindins (Absorption) 2) enhances calcium reabsorption in renal tubular cells
where is calcium absorbed?
duodenum and jejunum
what form is phosphate found in the foods?
easily hydrolyzable organic esteres
who often has low intake of calcium?
elderly and females
how is excess P controled?
excretion in kidneys: controlled by PTH, Vitamin D, FGF-23
what happens in osteomalacia?
failure to mineralize bone matrix. The organic matrix continues to be synthesized by functional osteoblasts so there is an increase in ratio of nonmineralized bone to mineralized bone. muscular weakness, bone tenderness. Increased risk of fracture the broken down bone does not become dense and hard
how is phosphorous found in the teeth?
fluoroapatite (made as fluoride, calcium, phosphate)
hematopoiesis
formation of red blood cells and white cells, bone precursor cells, fat cells, muscle cells
VDR are stimulated by
glucocorticoids, vitamin D, and PTH
What is a Z score?
good for comparing young adults and kids. Good to identify osteoporosis from hyper PTH, alcoholism
what is a storage form of phosphorous found in seeds
hexainositol phosphate broken down with phytase (but humans don't have it)
what is the role of phosphate in renal reabsorption of calcium?
high phosphate reduces calcium excretion, and thereby increases PTH response, and increases FGF 23 which inhibits renal calcitriol production
what is hyperphosphatemia?
high serum phosphate concentrations
role of sodium in renal reabsorption of calcium?
high sodium increases calcium excretion
what is in the inorganic/mineral phase of bone?
hydroxyapatite crystals
what is the effect of Vitamin D hormone?
increase calbindins in the small intestine (increases CA2+ absorption) increases bone formation such as bone osteoblasts enhances Ca2_ and Pi reabsorbtion in renal tubular cells increases mucosal cell uptake of phosphorus in the small intestine
how does FGF 23 affect phosphorous?
increases P excretion and and decreases calcitriol
low serum pH effect on PTH?
increases levels of PTH
how does FGF-23 influence calcium?
increases renal phosphate excretion and decreases vitamin D hormone kidney production
how does PTH affect phosphate?
increases urinary excretion of phosphate
most common symptom of hyperphosphatemia?
induced hypocalcemia other common symptoms: deposition of calcium phosphate, kidney injury
how does PTH act?
it responds to small declines in plasma calcium increase plasma calcium decreases plasma phosphate
where is phosphorous most actively absorbed?
jejunum
what does phosphorous help with?
kidney function, muscle contraction, normal heartbeat, nerve signaling
what can impair 1 hydroxylase activity
lead
where is DBP made?
liver
what is the net efficiency of calcium?
low in adults (15-30%) and up to 50% when calcium intake is low
signs of vitamin D deficiency
low serum Calcium and phosphate. elevated serum levels of bone alkaline phosphatase due to increased osteoblast activity. elevated PTH, increased osteoid and bone irregularities
what is hypophosphatemia?
low serum phosphate concentrations
Calcium
macro mineral >100 mgs/day
what negative affect calcium absorbtion?
phytate, oxalate, high fat with unesterified free fatty acids that form soaps with calcium and magnesium, hypo[achlorhydria], and poor upper GI motility
T score
predicts future fracture risk
Vitamin D biosynthesis
produced from cholesterol/sterols in the body by the photolytic action of UVB light 1st step: cholesterol --> 7 dehydrocholesterol in the skin
main food sources of phosphorous?
protein food groups
how is 25-OH-vitamin D 1-hydroxylase?
regulated by PTH, circulating concentrations of Ca and phosphate, FGF-23, 1-25(OH)2-D3 through negative feedback
What happens to calcidiol after the first hydroxylation?
released to circulation where it binds to DBP and goes to the kidney
where is vitamin D absorbed?
small intestine (ileum)
what does osteomalacia mean?
soft bones
how does PTH act on the small intestine?
stimulates 1,25OHD3 synthesis which results in increased calcium absorbtion
how does PTH act on the kidney?
stimulates Ca reabsorption in distal tubule and inhibits reabsorbtion of phosphate
how does PTh act on the bone?
stimulates resorption and release of calcium from the bone fluid compartment
what are the effects of an increase in FGF-23?
suppression of bone matrix formation, increased urinary phosphate excretion, inhibition of calcitriol production in the kidney considered a risk factor for fractures of the hip
where does VDR bind?
to VDRE
what are the two types of structures found within bone?
trabecular bone (spongy bone) at the end. and compact bone (shafts of long bone)
what are the two ways Ca2+ are absorbed?
transcellular and paracellular
how does FGF act?
via specific receptors and a transmembrane protein called klotho
what is the enzyme that does the first hydroxylation?
vitamin D 25-hydroxylase (not regulated)
How is the synthesis of osteocalcin increased?
vitamin D3
what is paracellular intake?
passive, nonsaturable process throughout the intestine happens when Calcium intake is high but vitamin D not involved
what is the most common naturally occurring form of phosphorus
phosphates (PO4)-3
what is the sixth most abundant element in the human body?
phosphorous
what are the two hydroxylations of Vitamin D biosynthesis?
1. in the liver producing 25 hydroxyvitamin D3 (calcidiol) 2. in the kidney producing 1,25 dihydroxyvitamin D3 (calcitriol)
what is the major homeostatic regulator of serum calcium?
PTH
What are the 3 hormones that regulate serum Calcium concentration?
PTH (major), 1,25-OH-D3, calcitonin (minor)
what hormones are involved with hormone mediated reabsorption?
PTH and vitamin D
What are commonly Vitamin D fortified foods?
milks, orange juice, baked goods
How does phosphorous exist at physiological pH
mixture of H3PO4 and HPO4-2
do calcium supplements work?
no because the extra calcium is absorbed by the bone and is instead excreted through the urine contributes to kidney stones or atherosclerotic plaques
Can you have excessive production of Vitamin D3, cholecalciferol?
no because there is a degradation pathway from pro-vitamin D --> non functional forms
what is the receptor for vitamin D?
nuclear hormone receptor "VDR"
what is the second hydroxylation?
occurs in the kidney, results in calcitriol (the active vitamin D hormone)
what is in the organic phase/matrix phase of bone?
osteocalcin, cross linked collagen fibers
how is phosphorous transported?
paracellular pathway