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Vitamin D metabolism

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Vitamin D metabolism Dr Salah Mansy Consultant Paediatrician Conquest Hospital Objectives Understand physiology and pathophysiology of vitamin D Clinical ... – PowerPoint PPT presentation

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Title: Vitamin D metabolism


1
Vitamin D metabolism
  • Dr Salah Mansy
  • Consultant Paediatrician
  • Conquest Hospital

2
Objectives
  • Understand physiology and pathophysiology of
    vitamin D
  • Clinical presentations of vit D
    deficiency/insufficiency
  • Prevention and treatment of vit D
    deficiency/insufficiency
  • Thoughts for the future

3
Human skeleton
  • Protein matrix osteoid (90), osteocalcin and
    other proteins
  • calcium phosphate, calcium carbonate, sodium,
    magnesium, and citrate
  • Dynamic

4
Definitions
  • Rickets only in growing children. Poor
    mineralisation before fusion of the epiphyses.
  • Osteomalacia poor mineralization at all ages.
  • All patients with rickets have osteomalacia, but
    not all patients with osteomalacia have rickets
  • Osteoporosis poor mineralization and loss of
    bone volume

5
Epidemiology
  • A disease of 19th and 20th century in northern
    Europe and the United States
  • Resurgence of vitamin D deficiency in UK
  • Recent prevalence data in UK children is lacking
  • Adult study
  • 46.6 of white adults are vit D deficient. Am J
    Clin Nutr 200785860-8
  • One in 8 white, 1 in 4 African Caribbean, 1 in 3
    Asian adults are vit D deficient. Ann Clin
    Biochem 2006 43468-73

6
Risk factors
  • Exclusively breast fed
  • Multiple short interval pregnancies
  • Vegetarian (or other non-fish eating) diet
  • Lack of sunlight exposure
  • Cultural influence on dress
  • Sedentary indoors lifestyle
  • Sunscreen use
  • Fear of cancer
  • Pigmented skin
  • Obesity
  • Malabsorption, short bowl or cholestatic liver
    disease
  • Use of anticonvulsants, rifampicin,
    cholestyramin, glucocorticoids or highly active
    antiretroviral treatment (HAART)

7
Sources
  • Ultraviolet B sunlight exposure 90 of supply
  • Oily fish
  • Cod liver oils
  • Infant formula milk (400 IU/L)
  • some breakfast cereals, breads and margarine
  • Breast milk low (1260 IU/L)
  • Egg yolk (20 IU)
  • Mushrooms (small quantities)

8
Table 2 Recommended Dietary Allowances (RDAs)
for Vitamin D 1
Age Male Female Pregnancy Lactation
012 months 400 IU (10 mcg) 400 IU (10 mcg)    
113 years 600 IU (15 mcg) 600 IU (15 mcg)    
1418 years 600 IU (15 mcg) 600 IU (15 mcg) 600 IU (15 mcg) 600 IU (15 mcg)
1950 years 600 IU (15 mcg) 600 IU (15 mcg) 600 IU (15 mcg) 600 IU (15 mcg)
5170 years 600 IU (15 mcg) 600 IU (15 mcg)    
gt70 years 800 IU (20 mcg) 800 IU (20 mcg)    
Adequate Intake (AI)
9
The metabolic pathway of vitamin D, indicating
its conversion to the hormone 1,25(OH)2D3 and to
24,25(OH)2D3. Vitamin D2 (ergosterol), of plant
origin, appears to undergo similar metabolic
steps.
10
Physiology
  • 1,25-D
  • Intestine marked increase in calcium absorption,
    less significant increase in phosphorus
    absorption ( most dietary phosphorus absorption
    is vitamin Dindependent)
  • Bone resorption
  • PTH secretion suppression (negative feedback
    loop)
  • Kidney inhibits its own synthesis and increases
    the synthesis of inactive metabolites
  • 25-D is the standard method for determining a
    patient's vitamin D status because there is
    little regulation of the liver hydroxylation step.

11
Physiology
  • Parathyroid hormone (PTH) and vitamin D are the
    principal regulators of calcium homeostasis
  • Calcitonin and PTH-related peptide (PTHrP) are
    important primarily in the fetus.
  • Phosphate homeostasis is regulated by the kidneys
    because intestinal phosphate absorption is nearly
    complete and renal excretion determines the serum
    level

12
Causes of Rickets
  • Vitamin D deficiency
  • Nutritional vitamin D deficiency
  • Congenital vitamin D deficiency
  • Secondary vitamin D deficiency 
  • Malabsorption 
  • Increased degradation 
  • Decreased liver 25-hydroxylase
  • Vitamin Ddependent rickets type 1
  • Vitamin Ddependent rickets type 2
  • Chronic renal failure
  • Calcium deficiency
  • Intake
  • Absorption
  • Rickets of prematurity
  • Phosphate deficiency
  • Intake
  • Absorption
  • Renal diseases
  • Renal tubular acidosis

13
Diagnosis History
  • History of poor growth, delayed walking, waddling
    gait, dental caries, pneumonia, and hypocalcaemia
    symptoms
  • Decrease dietary intake
  • Decrease skin synthesis clothing, skin
    pigmentation, sun screen, season
  • Malabsorption due to liver or intestinal disease
  • Renal disease
  • Drugs e.g. Phenobarbital, phenytoin,
    aluminium-containing antacids, rifampicin,
    cholestyramin, glucocorticoids or highly active
    antiretroviral treatment (HAART)
  • Maternal risk factors for nutritional vitamin D
    deficiency
  • Family history of genetic disorders, leg
    deformities, difficulties with walking, or
    unexplained short stature , unexplained sibling
    death (Cystinosis)

14
Clinical features General
  • Failure to thrive  
  • Listlessness  
  • Protruding abdomen  
  • Muscle weakness (especially proximal)  
  • Fractures

15
Clinical features Head  
  • Craniotabes 
  • Frontal bossing  
  • Delayed fontanelle closure  
  • Delayed dentition caries  
  • Alopecia (vitamin Ddependent rickets type 2)

16
Clinical features Chest
  • Rachitic rosary  
  • Harrison groove 
  • Respiratory infections and atelectasis

17
Clinical features Extremities
  • Leg pain
  • Enlargement of wrists and ankles  
  • Valgus or varus deformities 
  • Coxa vara  
  • Anterior bowing of the tibia and femur   
  • Windswept deformity (combination of valgus
    deformity of 1 leg with varus deformity of the
    other leg)  

18
Clinical features Back
  • Scoliosis 
  • Kyphosis  
  • Lordosis

19
Clinical features Hypocalcaemia symptoms
  • Tetany  
  • Stridor due to laryngeal spasm
  • Seizures Stebbing C, Mansy S, Kanabar D (2002)
    The first reported presentation of rickets with
    metabolic seizures. Hospital Medicine 63 690-691
     

20
(A) a normal child (B) a child with rickets
metaphyseal fraying and cupping of the distal
radius and ulna.
21
Cupping and fraying
22
Rosary beads of rickets
23
X-rays of the knees in a 7 yr old girl with
distal renal tubular acidosis and rickets. A, At
initial presentation, there is widening of the
growth plate and metaphyseal fraying. B, Dramatic
improvement after 4 mo of therapy with alkali.
24
a two-year old rickets sufferer, with a marked
genu varum, (bowing of the femurs) and decreased
bone opacity, suggesting poor bone mineralization
25
VDDR vitamin Ddependent rickets XLH X-linked
hypophosphatemic rickets ADHR autosomal dominant
hypophosphatemic rickets HHRH hereditary
hypophosphatemic rickets with hypercalicuria Pi
phosphorus RD relatively decreased (because it
should be increased given the concurrent
hypophosphatemia
26
Consequences of untreated vitamin D deficiency
  • Skeletal complications
  • Musculoskeletal pain particularly in adolescence.
    Arch Dis Child 201196694-6
  • Reduced whole body bone mineral content and bone
    mass even at 9 years of age. Lancet 2006
    36736-43
  • Hypertension, hyperglycaemia and metabolic
    syndrome in adolescents. Pediatrics 2009 Aug 3
  • Type 1 diabetes, multiple sclerosis, malignancy
    and schizophrenia. Pediatrics 2008122398-417
  • Cardiomyopathy (3 deaths in the last 10 years in
    UK). Heart 200894581-4

27
Threshold for intervention for vit D deficiency
  • 25-hydroxyvitamin D level reliably determine vit
    D status. Nutr Rev 200866S153-64
  • lt25 nmol/l severe deficiency treat
  • 25-50 nmol/l insufficiency supplementation
  • 51-75 nmol/l sufficiency lifestyle advice
  • gt250 nmol/l excess stop treatment
  • Arch Dis Child 2011,96614-615

28
Prevention of vit D deficiency in UK
  • Huge economic burden and preventive strategies
    are cost effective. Prog Biophys Mol Biol
    200999104-13
  • Healthy Start scheme 2006. http//www.healthystart
    .nhs.uk
  • Free vit D to economically disadvantaged children
    and young mothers
  • Restrictive qualification criterion for
    supplements
  • Only children under 4
  • Only mothers with a very limited income
  • Asylum seekers are not entitled
  • Inconsistent dissemination of message regarding
    supplementation to pregnant women
  • Poor availability of supplements

29
Prevention of vit D deficiency in UK
  • Recommendations for vit D supplementation have
    not generally been implemented. Update on Vitamin
    D. Position Statement by the Scientific Advisory
    Committee on Nutrician. 2007. http//www.sacn.gov.
    uk
  • Better targeting of health resources to antenatal
    care, pregnant mothers and at risk children
  • Extending the range of food fortified with vit D
  • Clarification of the risk associated with UV
    radiation against the risk of deficient vit D
    synthesis

30
Vit D preparations
  • Ergocalciferol (yeast derived D2)
  • Oily solution 3000 IU/ ml
  • Tablets 10 000 IU or 50 000 IU
  • Tablets calcium 400 mg and vitamin D 400 IU
  • Parenteral 300 000 IU/ ml
  • Colecalciferol (fish or lanoline derived D3)
  • Dalvit 400 IU/ 0.6 ml
  • Abidec 400 IU / 0.6ml
  • Healthy Start vitamin drops 300 IU/ 5drops
  • Tablets 20 000 IU
  • Alfacalcidol (one Alpha Hydroxycolecalciferol)
  • Oral/IV in persistent cases, renal, cholestatic
    liver disease

31
Treatment of deficiency
  • lt 6months 3000 IU daily for 8-12 weeks
  • gt 6 months 6000 IU daily for 8-12 weeks
  • gt 1 year 300,000600,000 IU orally or
    intramuscularly as 24 doses over 1 day
  • Adequate dietary calcium and phosphorus
  • Daily vitamin D intake of 400 IU/day

32
Treatment of insufficiency
  • lt 6 months 200-400 IU daily
  • gt 6 months 400-800 IU daily

33
Unanswered questions
  • Would eradication of vitamin D insufficiency in
    the UK reduce cancer incidence and improve cancer
    outcome?
  • Does poor vitamin D status cause obesity, or is
    it a consequence of obesity?
  • Are individuals genetically susceptible to
    vitamin D insufficiency or toxicity?
  • How much does vitamin D insufficiency contributes
    to north/south health inequalities?

34
Question time
35
Summary points
  • Vitamin D insufficiency is common in UK
  • Vitamin D deficiency presentation is different in
    different age group
  • Vitamin D deficiency is easy to treat
  • Vitamin D is linked to other health problems e.g.
    cardiovascular, DM type 2 etc.
  • Vitamin D insufficiency is preventable however
    robust measures are not yet in place

36
Thank you
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