VITAMIN D

Symptoms of acute toxicity are due to?

-Hypercalcemia

Cholecalciferol produced in the skin or ergocalciferol/cholecalciferol in the diet are both stored in the liver as?

-25-hydroxyvitamin D, which is the major circulating form of vitamin D

Recommended Daily Vitamin D Intake Infants

-400 IU/day

Recommended Daily Vitamin D Intake Adults (19-70 years)

-600 IU/day

Recommended Daily Vitamin D Intake Children (1-18 years)

-600 IU/day

Recommended Daily Vitamin D Intake Older adults (71+ years)

-800 IU/day

What can occur with excess intake of Vitamin D?

-Hypercalciuria and hypercalcemia -Toxicity typically does not occur at the recommended daily intake of supplementation, but may occur with consumption of inappropriately high doses of supplements

Where is 25-hydroxyvitamin D converted to its active form?

-In the kidney

Where is cholecalciferol (D3) stored?

-Liver

When does Rickets occur?

-Rickets occurs before epiphyseal fusion, when vitamin D deficiency leads to expansion of the growth plate and growth retardation

Where is the majority of the Vitamin D synthesized within the body?

-The majority of vitamin D is synthesized in the skin after exposure to ultraviolet light

What type of vitamin is Vitamin D?

-Vitamin D is a lipid-soluble vitamin

Vitamin D can come from the diet in the form of?

-cholecalciferol (D3) or ergocalciferol (D2)

7-dehydrocholesterol is converted to what?

-cholecalciferol (vitamin D3) after light exposure

What are the symptoms of acute vitamin D toxicity?

-confusion -polyuria -anorexia -vomiting -muscle weakness

What decreases the production of 1-α-hydroxylase?

-high serum calcium -high serum phosphorous

Regardless of cause, the clinical manifestations of vitamin D deficiency are largely a consequence of what?

-impaired intestinal calcium absorption

Commonly fortified foods include?

-infant formula, milk and breakfast cereals -Vitamin D supplements, usually containing cholecalciferol, are widely available as well.

How does melanin affect cholecalciferol production?

-melanin reduces cholecalciferol production

DEFICIENCY Medications that induce P450 enzymes

-metabolize vitamin D into inactive metabolites. -The most common medications are phenytoin, phenobarbital, carbamezapine, oxcarbazepine, isoniazid, theophylline and rifampin.

What can chronic vitamin D intoxication result in?

-nephrocalcinosis -bone demineralization -pain

Adults with severe vitamin D deficiency develop?

-osteomalacia

What increases the production of 1-α-hydroxylase?

-parathyroid hormone -low serum calcium -low serum phosphorous

Vitamin D plays an essential role in what processes?

-plays an essential role in bone metabolism, calcium homeostasis and phosphorous homeostasis

DEFICIENCY Chronic liver disease

-results in a decreased synthesis of 25-hydroxyvitamin D and inadequate stores

DEFICIENCY Chronic kidney disease

-results in a deficiency of 1-α-hydroxylase with inadequate conversion to the active form

Children with severe vitamin D deficiency develop?

-rickets or osteomalacia

What is the main target tissue of 1,25-dihydroxyvitamin D?

-the gastrointestinal enterocyte

The length of daily exposure necessary for sufficient vitamin D production is dependent upon what?

-variable from individual to individual, depending upon the intensity of the sun (world location, time of day, season) and the individual (melanin reduces cholecalciferol production)

What does 1,25-dihydroxyvitamin D do in the GI enterocyte?

-where vitamin D binding causes enterocyte differentiation and synthesis of calcium receptors and binding proteins, increasing calcium absorption, and to a lesser degree phosphorous absorption.

What is the active form of 25-hydroxyvitamin D?

-1,25-dihydroxyvitamin D

What is the MOA of 1,25-dihydroxyvitamin D?

-1,25-dihydroxyvitamin D binds intracellular receptors in target tissues and regulates gene transcription

What enzyme converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D?

-1-α-hydroxylase

When does Osteomalacia occur?

-Osteomalacia occurs after epiphyseal closure, and vitamin D deficiency leads to impaired mineralization of bone matrix proteins

How can Vitamin D derived?

-Vitamin D can either be made from the skin by exposure to sunlight or can be provided pre-formed in the diet -Vitamin D is found in very few foods naturally, so most dietary sources are artificially supplemented

Why is Vitamin D deficiency common in breastfed infants?

-Vitamin D deficiency is common in breastfed infants, as breastmilk alone does not provide infants with an adequate intake of vitamin D -Vitamin D deficiency rickets in breastfed infants is rare, but it can occur if an infant does not receive additional vitamin D from a vitamin supplement or from adequate exposure to sunlight. -Infant formula is fortified with vitamin D, so additional supplementation is not necessary.

DEFICIENCY Malabsorption

-from any disorder can impair absorption of dietary vitamin D (celiac disease, pancreatic insufficiency, bariatric surgery, short bowel syndrome, etc.)

DEFICIENCY Inadequate supply

-usually due to lack of sunlight exposure and insufficient dietary sources. -Young children and older adults are at particular risk for inadequate sun exposure, and subsequent vitamin D deficiency.