Defficiency states of

dr mukesh kumar

VITAMIN D

What is Vitamin D?

• Vitamin D is a fat-soluble pro-hormoneo Sterol derivative

• 2 forms of vitamin Do Vitamin D2 (Ergocalciferol)o Vitamin D3 (Cholecalciferol)

• Pro-hormone is converted into its biologically active metabolite: calcitriol

• Vitamin D may be obtained from the diet and through skin exposure to sunlight (UV light)

Uses for Vitamin D

• Maintains structural integrity of bones & bone growth by regulating use of calcium + phosphate (bone turnover)

• Maintains serum calcium homeostasis

• Research shows that Vitamin D may play a role in immune function and protection from chronic diseases

Synthesis and Metabolism

• Ergocalciferol (D2) synthesized in plant and fungi when ergosterol undergoes photolysis under UV light

• Cholecalciferol (D3) synthesized in skin of animals by photolysis of 7-dehydrocholesterol

• Bioactivation occurs through 2 steps• Hydroxylation in liver produces calcidiol• Hydroxylation in kidney produces calcitriol

Mechanism of Action• Calcitriol is transported through the circulatory

system by vitamin D binding protein and albumin

• Diffuses into the nucleus of target cells and binds to Vitamin D receptor (VDR)

• VDR associates with Retinoic Acid X receptor (RXR) – forms VDR-RXR complex

• VDR-RXR binds to DNA sequences called Vitamin D Response Elements (VDREs) to modulate the expression of >50 genes

Mechanism of Action

• VDRE regulated gene expression leads to:

o Increased dietary calcium and phosphorus absorption in small intestine

o Increased renal reabsorption of calcium

o Increased renal excretion of phosphate

o Increased resorption of bone to increase serum calcium levels

Natural Food Sources:Egg Yolk 20-25/yolk

Shrimp 152/100gm

Tuna 224-332/100gm

Canned salmon 624/100gm

Natural Food Sources:Egg Yolk 20-25/yolk

Shrimp 152/100gm

Tuna 224-332/100gm

Canned salmon 624/100gm

Sources of Vitamin D- Food

Fortified Food Sources:

Vitamin D milk 400/L

Formula 400/L

Cereal 40/serving

Yogurt 89/100gm

Fortified Food Sources:

Vitamin D milk 400/L

Formula 400/L

Cereal 40/serving

Yogurt 89/100gm

Less than 10%!

Less than 10%!

Sources of Vitamin D - Sun

UV light converts cholesterol in skin into D3 Dark skinned people

require a longer duration of sun exposure for adequate production of Vitamin D

Less UV light is available in the winter months, higher latitudes, and with cloud cover and air pollution

Vitamin D sources

• Fortified foods (milk and orange juice)

• Fish liver oilo Cod liver oil contains over 1000IU/tablespoon

• Fatty fish (salmon, tuna)

• Liver, beef

• Sunlight exposureo 5-30 minutes in direct sunlight at mid-day

• Supplements

Recommended Dietary Allowances

Age group Recommended Dietary Allowance (RDA) per day

Tolerable Upper Intake Level (UL) per day

Infants 0-6 months 400 IU  (10 mcg) * 1000 IU (25 mcg)

Infants 7-12 months 400 IU  (10 mcg) * 1500 IU (38 mcg)

Children 1-3 years 600 IU (15 mcg) 2500 IU (63 mcg)

Children 4-8 years 600 IU (15 mcg) 3000 IU (75 mcg)

Children and Adults 9-70 years

600 IU (15 mcg) 4000 IU (100 mcg)

Adults > 70 years 800 IU (20 mcg) 4000 IU (100 mcg)

Pregnancy & Lactation 600 IU (15 mcg) 4000 IU (100 mcg)

*Adequate intake rather then RDARetrieved from Health Canada. (2010, December 13). Vitamin D and Calcium: Updated Dietary Reference Index

Why do breast fed babies need supplemental Vitamin D?

Breast milk contains little vitamin D 25-78 IU/day Rates of vitamin D deficiency

in breastfed infants up to 78% in winter

Limited sun exposure

: infants less than 6 months should be kept out of direct sunlight

Why do breast fed babies need supplemental Vitamin D?

High rates of Vitamin D maternal deficiency

Pittsburgh study at birth: Black women

29% deficient 54% insufficient

White women 5% deficient 42% insufficient

Preventing Vitamin D deficiency

Breastfed and partially breastfed infants should be supplemented with 400 IU/day of vitamin D beginning in the first few days of life.

Supplementation should be continued unless the infants is weaned to at least 1L/day of vitamin D-fortified formula or fortified milk.

TriViSol contains 400 IU per ml

Vitamin D Deficient States

Rickets Peak incidence 3-18

months Defective bone growth

due to lack of mineralization at growth plate

Hypocalcemic seizures Growth failure, lethargy,

irritability Delay in gross motor

development, bone pain

Vitamin D Deficient states

RicketsBowing or widening of physis

Costochondral beading (rachitic rosary)

Craniotabes

Delayed closure of anterior fontanel

Dental abnormalities

Flaring of ribs at diaphragm

Vitamin D Deficiency

• Inadequate exposure to sunlight (UV rays)

• Inadequate intake from diet

• Deficiencies in GI tract absorption

• Kidney or liver disorders

Retrieved from: http://emedicine.medscape.com/article/412862-overview

Rickets (children)

• Pathophysiologyo Rickets is failure of bone to mineralizeo Growth plates of bone continue to enlarge while

the load on the limbs continues to increase In the absence of mineralization, limbs become

bowed

• Symptomso Characterized by stunted growth and deformed

boneso In infants, rickets may result in the delayed closure

of fontanelles (soft spots on baby’s head)

Treatment

o Vitamin D and calcium supplementso Corrective surgery or bracing for skeletal

deformities

Vitamin D Deficient States

Adult Vitamin D deficiency implicated in Increased infections Autoimmune diseases (Multiple

Sclerosis, Rheumatoid arthritis) Cancer Type 2 Diabetes Bipolar disorder, schizophrenia

Type I Diabetes in childhood Maternal Vitamin D status associated

with adverse outcomes of pregnancy – miscarriage, preeclampsia, preterm birth

Osteomalacia (adult)

• Pathophysiologyo Impaired bone mineralizationo Adult bones are in constant state of turnover and

new bones are brittle and thin

• Symptomso Bone pain (lower spine, pelvis, hips, legs, ribs)o May result in muscle weakness

• Treatmento Vitamin D supplementso Treating conditions affecting vitamin D absorption

and metabolism

Osteoporosis• Pathophysiology

o Rate of bone loss is greater than rate of bone formation – gradual loss of bone mass

o Bone strength is compromised – increased risk of fracture

• Symptomso Non-specific chronic back paino Height losso Bone fractures occur more easily

• Treatment and Preventiono Maximizing/maintaining existing bone

mass density Calcium and vitamin D supplements,

weight-bearing exerciseo Minimize risk of falls

Laboratory diagnosis

Vitamin D status- 25(OH)-D levels•Deficiency <37.5 nmol/mL•Insufficiency 37.5-50 nmol/mL•Sufficiency>50 (?) nmol/mL

Severe deficiency states associated with:

Ca,PO4,

Alk Phos, PTH

Summary Slide

Vitamin D (fat-soluble, pro-hormone): ergocalciferol (D2) and cholecalciferol (D3)

• converted to active hormonal form, calcitriol by metabolism in liver and kidney

• Targets: bone, kidney and GI tract• Function: maintains serum calcium levels & integrity of bones growth

via calcium regulation

Deficiency – leads to rickets, osteomalacia and osteoporosis• Lack of calcium leads to impaired bone mineralization and loss of

bone mass• Treatment: Increase vitamin D and calcium intake, and increase bone

mass density