MSK DLA 47: Vitamin D

What is the active form of Cholecalciferol (Vitamin D)? AKA?

1, 25 dihydroxy Cholecalciferol (1, 25 DHCC) Calcitrol

What are the characteristic features of children with Vitamin D deficiencty?

1- Bow-leg deformity 2- Rachitic rosary (overgrowth at costochondral junction) 3- Pigeon chest deformity 4- Frontal bossing 5- Delayed closure of fontanelle 6- Delayed teething in infants

What are the 3 lab findings characteristic of Vitamin D deficiency?

1- Elevated serum ALP (alkaline phosphate) 2- Low serum Calcium levels 3- Low serum Phosphate levels

What are the 3 lab findings to people with Osteomalacia?

1- Elevated serum ALP (alkaline phosphate) 2- Low serum Calcium levels 3- Low serum Phosphate levels

What are the 3 main risk factors for developing Vitamin D deficiency?

1- Inadequate exposure to sunlight - common during winter; in elderly 2- Nutritional deficiency - decreased intake/ fat malabsorption/ exclusively breast fed infants 3- Chronic renal disease, chronic liver disease - results in decreased hydroxylation of vitamin D

What are the 5 factors that can affect Vitamin D formation in the Skin?

1- Increased Melanin production reduces its formation 2- Time of exposure and latitude 3- Amount of exposed skin (sunscreen reduces formation) 4- Winter months and latitude

Vitamin D deficiency can be improved by supplementing what 2 things?

1- Vitamin D 2- Calcium

What enzyme is responsible for the conversion of 25-Hydroxycholecalciferol to 1,25 dihydroxycholecalciferol in the kidney? What 2 factors upregulate this enzyme?

1-Hydroxylase 1- Parathyroid hormone (parathormone) 2- Low plasma Calcium

What is the regulated step in 1,25 dihydroxycholecalciferol formation?

1-Hydroxylase in the kidney

1,25-Dihydroxycholecalciferol (Calcitriol) can be converted into its inactive form by the action of what enzyme? What is its inactive form?

24 Hydroxylase 1,24,25-hydroxycholecalciferol (Inactive)

What enzyme is responsible for the conversion of Cholecalciferol to 25-Hydroxycholecalciferol in the liver?

25-Hydroxylase

What is the precursor for Cholecalciferol (Vitamin D3) synthesis in the skin? What is it an intermediate in? Adequate exposure to what can prevent Vitamin D deficiency?

7- dehydrocholesterol Cholesterol synthesis Sunlight

Practice Q1

Ans: D

Practice Q2

Ans: D

How does Vitamin D increase serum Phosphate levels?

By increasing its absorption from the intestine •In the presence of vitamin D, serum calcium and phosphate are elevated - Increases the tendency to form bone mineral (Vitamin D facilitates mineralization, when serum calcium and phosphate are adequate)

Prolonged hypervitaminosis D (prescription medications) can lead to what?

Calcification in soft tissue eg: Kidney

Vitamin D deficiency in children can also occur due to a mutation in what? What does this mutation cause? As a result children have?

Calcitriol receptor Calcitriol is unable to bind to its receptor in the intestinal mucosal cells --> reduced binding of Calcitriol Increased levels of Calcitriol

Patients with vitamin D deficiency have low serum ..... and low serum ..... levels and ......... bone mineralization

Calcium Phosphate decreased

Vitamin D deficiency in children due to mutation in Calcitriol receptor can lead to decreased levels of? Increased levels of?

Calcium and Phosphate 1,25 hydroxyvitamin D •Compare to vitamin D deficient rickets, which has low serum calcium and phosphate and low levels of 25-hydroxyvitamin D

Vitamin D stimulate or represses absorption of .... and .... in the Intestine? It does this by increasing the synthesis of what protein?

Calcium and Phosphate Calbindin - specific calcium binding protein

What does Vitamin D stimulate the mobilization of in the bones? It does this in the presence of what hormone?

Calcium and Phosphate Parathyroid hormone

What does Vitamin D inhibit the excretion of in the Kidney? It does this by stimulating?

Calcium excretion Parathyroid dependent Calcium reabsorption

What is Vitamin D (Calciferol) found in plants known as? Animals?

Ergocalciferol (Vitamin D2) Cholecalciferol (Vitamin D3)

What is Hypervitaminosis D characterized by? Due to? Vitamin D also increases the absorption of what?

Hypercalcemia Increased Calcium absorption from the diet Phosphate

Where are the Intracellular receptor proteins that 1,25-Dihydroxycholecalciferol binds to located? Binding forms? That complex interacts with what and where? What can that then stimulate/repress? Synthesis of what is increased?

Intestinal Mucosal cells 1,25-DHCC receptor complex DNA Hormone response element in the nucleus of the intestine Stimulate/repress gene expression Calbindins

What condition occurs as a result of Vitamin D deficiency in adults? Causes bones to become what? - Which makes it susceptible to? It may present in patients as?

Osteomalacia Demineralized Fractures Non-specific bone pain •Osteomalacia can be secondary to reduced exposure to sunlight, dietary deficiency, renal disease or liver disease

Vitamin D deficiency stimulate the secretion of what hormone? What effect can that have on the bone?

Parathyroid hormone Demineralization of the bone

Vitamin D deficiency results in what condition in children? How does it occur? What does it cause?

Rickets Decreased calcium absorption from the diet → Decreased serum calcium →↑Parathyroid hormone release → ↑demineralization of bone Demineralization of bone

What are the steps involved in the conversion of 7-dehydrocholesterol (precursor of Cholecalciferol(vitD)) to the active form of Vitamin D 1,25 dihydroxycholecalciferol? What are the locations where they occur?

Skin: 1- 7- dehydrocholesterol --> Cholecalciferol via Sunlight Liver: 2- Cholecalciferol --> 25-hydroxycholecalciferol via 25-Hydroxylase Kidney: 3- 25-hydroxycholecalciferol --> 1,25 dihydroxycholecalciferol (Calcitrol) via 1-Hydroxylase

In Hypervitaminosis the increase in serum calcium and phosphate results in an increased tendency for ?

Soft tissue (ectopic) mineralization

What type of Vitamin D deficiency is more common in the population ie Teens, young adults and elderly? ) In teens and young adults vitamin D deficiency affects the attainment of?

Subclinical Vitamin D deficiency Peak bone mass