Vitamin D in Children & Adolescents Flashcards
1
Q
What are features of Vitamin D?
A
- Synthesised in the body
- Hormone that regulates and control the synthesis of active form of Vitamin D
- Produced and released by a cell or a gland, and circulates in the body affecting cellular function in other parts of the body
2
Q
What are forms of Vitamin D?
A
Vitamin D2
- Plant source
- Ergocalciferol- Irradiation of yeast
Vitamin D3
- Animal Source
- Cholecalciferol – Irradiation of ianonin extraction from sheep wool
- Longer half-life than Vitamin D2. Relevant if large stat doses are considered
3
Q
What are the sources and metabolism of Vitamin D?
A
- Endogenous Vitamin D is activated by Solar UV-B’s interaction with the skin
- Dietary source Vitamin D are in oily fish (salmon, mackerel, herring), eggs, fish oils and fortified foods.
- These is are then converted to 25 hydroxy vitamin D by the liver
- Through 1α hydroxylase, the 25-Hydroxy Vitamin D is converted to 1,25 Dihydroxy Vitamin D in the kidney
- 1α hydroxylase is activated by PTH, Decreased Calcium, Decreased Phosphate and FGF23
4
Q
What are factors controlling Endogenous Vitamin D Synthesis?
A
- Intensity of sunlight
- Exposure of skin to sunlight
- Skin Pigmentation
- Ageing
5
Q
How is Vitamin D endogenously made?
A
- Solar UVB is absorbed by the skin
- This converts 7-dehydrocholesterol to Previtamin D
- Previtamin D is converted slowly to Cholecalciferol
- Continued sun exposure leads to inactivation of lumisterol and tachysterol
6
Q
How does 1,25 (OH)2D regulate phosphate and calcium?
A
- Increase Calcium and Phosphorus absorption through the intestine
- Promote mineralisation indirectly in the bone
- In the kidney, promotes calcium reabsorption mediated through PTH
7
Q
What is the physiological response of Vitamin D deficiency?
A
- Low Vitamin 1,25 Hydroxyvitamin D leads to decreased calcium absorption from the gut. The serum Calcium then decreases
- There is increased PTH as a result leading to mobilisation of calcium and phosphate
- This is caused by conversion of 25 Hydroxyvitamin D to 1,25 Hydroxyvitamin D which leads to increased calcium absorption from the gut. Serum calcium then normalises
- Definition of vitamin D deficiency & sufficiency based on serum 25(OH)D concentrations
8
Q
What is the biochemistry of Vitamin D deficiency?
A
Early vitamin D deficiency:
- 25 (OH)D ↓
- Ca Normal
- PTH ↑
- Phosphate ↓
- 1,25(OH)2D ↑
- ALP ↑
Severe vitamin D deficiency:
- 25(OH)D ↓ ↓
- Ca ↓
- PTH ↑ ↑
- P ↓ ↓
- 1,25-(OH)2D ↓
- ALP ↑ ↑
9
Q
Which factors contribute to development of Vitamin D deficiency?
A
- Residence in Northern or Southern Latitudes
- Pigmented skin
- Sun blocking creams – Factor 8 ↓ Vit D synthesis by >95%
- Sunshine avoidance for religious or cultural reasons
- Cloud Cover & Atmospheric Pollution
- Obesity
- Genetic propensity
- Low dietary Calcium & High Fibre diets
10
Q
How does a low calcium and high fibre diet affect the Vitamin D status?
A
- High fibre & phytic acid reduce dietary Ca intake
- High Phosphate diet reduces Ca/P ratio, reducing serum Ca
- Low Ca intake leads to secondary hyperparathyroidism & raised serum 1,25(OH)2D concentration
- Raised serum 1,25(OH)2D concentration degrades 25OH to inactive 24,25(OH)2 D, thereby depleting body stores of vitamin D
11
Q
What are musculoskeletal manifestations of vitamin D deficiency?
A
- Rickets in growing children and osteomalacia in adolescents and adults
- Children and adolescents present with aches and pains
- Muscle strength improves with Vitamin D and calcium supplements
12
Q
What are causes of Vitamin D deficiency?
A
- Sunscreen
- Melanin
- Latitude
- Winter
- Hepatic Failure
- Renal Failure
- Nephrotic Syndrome
- Obesity
- Medications and supplements: Antiseizure drugs, Glucocorticoids, Rifampicin, High active antiretroviral, St John’sWart
- Malabsorption: Crohn’s Disease, Whipple’s Disease, Cystic Fibrosis, Coeliac Disease, Liver disease
13
Q
What are consequences of Vitamin D deficiency?
A
- Infections: Tuberculosis, Influenza, Upper Respiratory tract infections
- Lung Disease: Forced expiratory volume in one second, Asthma and Wheezing disease, Hypertension, Cardiovascular Disease
- Autoimmune Disease: Type 1 diabetes, Multiple Sclerosis, Crohn’s Disease, Rheumatoid Arthritis
- Cancer: Breast, Colon, Prostate, Pancreas
- Type 2 Diabetes metabolic syndrome
- Schizophrenia/Depression
- Muscle weakness and aches
- Osteoporosis
- Osteoarthritis
- Osteomalacia (bone pain), Pseudofractures
- Rickets
14
Q
What is Rickets?
A
- Disease of the growing child
- Impaired mineralisation of the growth plate & osteoid
- Low serum phosphate is fundamental to pathogenesis of rickets. Vitamin D deficiency leads to renal phosphate wastage then hypophosphatemia.
- There is impaired apoptosis of terminally differentiated chondrocytes in the growth plate responsible for clinical & radiological sign of rickets
15
Q
What are types of Rickets?
A
Calcipaenic Rickets (Vitamin D related Rickets)
- Vitamin D Deficiency
- Impaired Hepatic 25-hydroxylation
- Impaired Renal 1α-hydroxylation of 25(OH)D
- End organ resistance to 1,25(OH)2D
Hypophosphataemic Rickets
- X-linked Dominant (PHEX gene mutation)
- Autosomal Dominant (FGF23 mutation)
- Autosomal Recessive Type 1 (DMP1mutation)
- Autosomal Recessive Type 2 (ENPP1mutation)
- With Hypercalciuria (SLC34A3 gene mutation.
- Associated with: McCune-Albright syndrome, Tumour induced osteomalacia, Linear nevus sebaceous syndrome
