Vitamin D, Calcium, Phosphorous

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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


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