Vitamin D
PTH stimulates _________ in kidney (conversion of 25-OH D to 1,25-(OH)2 D3
1-hydroxylase
Serum 25-OH D concentrations between about ___ and ___ ng/mL are generally thought to be sufficient to maintain health
30 and 40 ng/mL
1 µg cholecalciferol= ___ IU
40 IU
What is Rickets?
Failure of bone to mineralize -long bones of legs bow -knees knock as weight-bearing activities begin (walking) -spine becomes curved and pelvic and thoracic deformities
T/F: Dietary Vitamin D requires digestion before absorption
False
Vitamin D toxicity is ____ due to excessive exposure to sunlight
NOT
Elevated serum ____ concentrations, along with Calcitriol, direct the mobilization of calcium out of the bone to raise serum calcium concentrations to within a normal range -May be mediated by calcitriol-induced cell differentiation of hemopoietic cells to _________
PTH osteoclasts
What is the Vitamin D deficiency in infants and children?
Rickets
Many tumors have been found to contain ____________ (i.e. breast, lung, skin (melanoma), colon, and bone)
Vitamin D Receptors (VDR)
The ____ is the largest single pool and represents the major "storage site" of the vitamin as 25-OH D
blood
Mature osteoclasts release HCl, alkaline phosphatase, collagenase, and other hydrolytic enzymes and substances, which dissolve and catabolize (eat away at) the _______
bone matrix
Osteoclasts mediate _________
bone resorption (breaking down tissues in the bones)
The primary function of calcitriol in the intestine is to increase the absorption of ______ and ______
calcium and phosphorous
Calcitriol and Intestine cont...--> These proteins act at the brush border, in the _______, and at the __________ of the intestinal cells, esp. in the duodenum and jejunum, to promote calcium absoption
cytosol, basolateral membrane
Elevated serum calcitriol and elevated serum Ca++ cause ______ in PTH through feedback loops
decrease
Circulating 25-OH D concentrations reflect vitamin D status, which varies depending on both ________ and ________
dietary vitamin D intake and sun exposure
Calcitriol and Intestine cont...--> As the result of this interaction, selective DNA transcriptions occur that result in the biosynthesis of new mRNA molecules. These mRNA molecules are then translated on the ___________ into selected proteins
endoplasmic reticulum
The net effect of these bone demineralization actions is an _____ in serum calcium (and phosphorous) concentrations at the expense of the bone
increase
Para-thyroid hormone (PTH) is released when you have ___ calcium levels in the blood
low
Dietary Vitamin D is absorbed from a ______, in association with fat and with the aid of bile, by _______ diffusion into the intestinal cell
micelle, passive
Exposure to sunlight converts some of 7-dehydrocholesterol to __________
previtamin D3
The geographic distribution of colon cancer and breast cancer is similar to the historic geographic distribution of _________
rickets
Calcitriol acts on target tissues causing serum Ca level to ____
rise
Anterior fontanel normally closes by the end of the ____ year
second
Lower serum vitamin D thought to be due to ___________ in fat cells
seqestration: biological processes in which an organism accumulates a compound or tissue
Calcitriol functions as a ______ hormone
steroid
A hormone produced by thyroid gland and released when blood calcium levels rise above normal. Promotes mineralization of calcium and phosphorous in bones
Calcitonin
The absence of a _____ has been associated with a five-fold increased likelihood of vitamin D deficiency
jejunum
Calcitriol triggers differentiation of stem cells to ________
osteoclasts
Calcitriol decreases transcription of the gene for __________ hormone
preparathyroid
Protein found in bone matrix and dentine; secreted by osteoblasts and associated with new bone formation
Osteocalcin
What is the Vitamin D deficiency in adults?
Osteomalacia (soft bone)
In the intestine, Calcitriol increases activity of brush border ______________
alkaline phosphatase
Calcitriol and Intestine--> Calcitriol is transported into the _______ and carried into the nucleus, where it interacts with nuclear ____ to directly regulate specific genes encoding for proteins involved in calcium uptake and transport
enterocyte, VDRs
Posterior fontanel normally closes by the end of the _____ year
first
The major target tissues of Calcitriol are ________, ______ and _______
intestine, kidney, and bone
What are the forms of Vitamin D?
-Vitamin D3 (Cholecalciferol) -Vitamin D2 (Ergocalciferol)
What is the function of brush border alkaline phosphatase?
-hydrolyzes phosphate ester bonds releasing P for absorption -may increase activity of carrier involved in P absorption
Calcitriol functions in powerpoint
.
Vitamin D is converted to _________ and then further catabolized and excreted in bile
1,24,25-(OH)3 D3
________ induces cell differentiation and/or inhibit proliferation of a number of cancerous and noncancerous cell types maintained in cell culture
1,25(OH)2D
What is the active form of Vitamin D?
1,25-(OH)2 D3 (Calcitriol)
Vitamin 25-OH D has a half life of about ___-___ weeks or more
2-3 weeks
What is the Vitamin D recommendation for pregnant women?
2000 IU (Canadian Pediatric Society)
Plasma concentration of 25-OH D3: Average of ___-___ ng/mL Range __-__ ng/mL Levels < ___ ng/mL indicative of deficiency Levels > ___ ng/mL associated with toxicity
25-30 ng/mL 8-60 ng/mL <10 ng/mL >150 ng/mL
Calcitriol is transported to target tissues via _____
DBP
_____ is the major route of Vitamin D excretion
Feces
An open space in the top of a baby's skull before the bones have grown together. In rickets, the closing of this is delayed
Fontanel
Which organs activate D3?
Liver and kidneys
What is the targeted tissue for Multiple Sclerosis (MS)?
Myelin producing cells of CNS
What is the assessment of nutriture for Vitamin D?
Plasma concentration of 25-OH D3
Evidence that Calcitriol inhibits cancer cell proliferation and growth and stimulates epidermal __________, while preventing _________
cell differentiation, proliferation
Calcitriol along with Vitamin K may be important in the synthesis of __________
osteocalcin
7-dehydrocholesterol is made in ______ glands of skin and secreted onto the surface and then reabsorbed into various layers of the skin
sebaceous
Structurally, Vitamin D is derived from a steroid and is considered to be a ________ because one of its four rings is broken
seco-steroid
<___% of metabolites are excreted in urine
<5%
What is the targeted tissue for Insulin-dependent diabetes mellitus (IDDM)?
Beta cells of the pancreas
What is the targeted tissue for Rheumatoid arthritis (RA)?
Collaged producing cells of the joints
_________ stimulates the secretion of PTH from parathyroid gland
Hypocalcemia
Elevated serum calcium inhibits ____ secretion (long,indirect feedback loop)
PTH
In the kidneys, Calcitriol works with ____ in increasing calcium and phosphorous absorption
PTH
What is Osteomalacia?
Soft bone -impaired Ca absorption -mineralization of bone is impaired -bone matrix becomes demineralized- bone pain and softening
The American Academy of Pediatrics currently recommends _____ IU/d of vitamin D for all infants, children, and adolescents
400 IU
Taking ____ IUs of vitamin D- about the standard dose in most multivitamins- reduced the risk of pancreatic cancer by ___%
450 IUs, 43%
What is the UL for Vitamin D for adults 19 years and older?
100 mcg= 4000 IU
What is the DRI of Vitamin D for individuals who are 70+
15 µg/d
What are some food sources of Vitamin D?
-Eggs, butter, liver, fatty fish -Fortified products like milk and margarine
Which diseases/conditions increase the risk of Vitamin D deficiency?
-Fat malabsorption -Disorders affecting parathyroid gland, liver and/or kidney -Infants on breast milk -Aging may reduce synthesis of cholecalciferol -Lack of sunlight (geographical location, dark skin, Burka) -Diet, vega, lacto-vegetarian
In the kidneys, 1-hydroxylase is regulated by many factors, including:
-PTH and low blood Ca++ stimulate -High dietary P intake decreases activity (less calcitriol is made) -Sufficient amounts of calcitriol inhibit activity
What are the sources of Vitamin D?
-Sunlight -Animal products (primary food source) -Plants
What are the two characteristics of cancer cells?
1. Lack of differentiation (specialization) 2. Their rapid growth or proliferation (increase in numbers)
~10 minutes of summer sun on hands and face produces ___µg (400 IU) of cholecaliferol
10 µg
What is the DRI of Vitamin D for individuals who are 51-70 years old?
10 µg/d
Doses of _________ IU/d of Vitamin D may result in hypercalcemia
10,000 IU/d
What is the DRI of Vitamin D for individuals ages 0-50?
5 µg/d (200 IU)
About ___% of dietary vitamin D is absorbed
50%
Vitamin D contains 3 intact rings (A, C, and D) with a break in the B ring between carbons ___ and ___
9 and 10
_______ vitamin D is most likely to cause toxic reactions when the AI is chronically exceeded -Small multiples (__ x AI) may be toxic
Exogenous 5 x AI
Calcification of soft tissues (kidney, heart, lungs and blood vessels) as well as HTN, anorexia, nausea, renal failure, death
Hypercalcemia
_______ is a risk factor for Vitamin D deficiency
Obesity
T/F: There is no difference in capacity of skin to synthesize vitamin D in obese vs. non-obese
True
Vitamin D3 is found in _____ and Vitamin D2 is found in ______
animals, plants