Vitamin D & Rickets

2. Vitamin D & Rickets Dr Piyush B Tailor Assistant Professor Department Of Biochemistry Govt. Medical College Surat

3. Vitamin D • Vitamin D2 = ergocalciferol • Completely synthetic form produced by the irradiation of the plant steroid ergosterol • Vitamin D3 = cholecalciferol • Produced photochemically by the action of sunlight or ultraviolet light • Precursor sterol 7-dehydrocholesterol • Vitamin D = calciferol

4. VITAMIN D • Humans & animal utilize only vitamin D3 & they can produce it inside their bodies from cholesterol. • Cholesterol is converted to 7-dehydro-cholesterol (7DC), which is a precursor of vitamin D3.

5. VITAMIN D • Exposure to the ultraviolet rays in the sunlight convert 7DC to cholecalciferol. • Vitamin D3 is metabolically inactive until it is hydroxylated in the kidney & the liver to the active form 1,25 Dihydroxycholecalciferol. • 1,25 DHC acts as a hormone rather than a vitamin, endocrine & paracrine properties.

8. Formation of Vitamin D • Skin (UV light) • 7-dehydro cholesterol  Vitamin D3 • Ergosterol  Vitamin D2 • Liver • OH-group added • 25-Hydroxy vitamin D3 • Storage form of vitamin (~3 months storage in liver) • Kidney • OH-group added by 1-hydroxylase • 1,25-dihydroxy vitamin D3 • Active form of vitamin D, a “steroid hormone” • OH-group added by 24-hydroxylase • 24,25-dihydroxy vitamin D3 • Inactive form of vitamin D, ready for excretion

9. FUNCTIONS • Calcium metabolism: vitamin D enhances calcium absorption in the gut & renal tubules. • Cell differentiation: particularly of collagen & skin epithelium • Immunity: important for Cell Mediated Immunity & coordination of the immune response.

10. Vitamin D - Functions • Bone development • Osteoclastic activity • Calcium absorption (small intestine) • Calcium resorption (bone and kidney) • Maintain blood calcium levels • Phosphorus absorption (small intestine) • Hormone • Regulation of gene expression • Cell growth

11. Vitamin D Functions

12. Groff & Gropper, 2000 Vitamin D Affects Absorption of Dietary Calcium • 1,25-(OH)2 D binds to vitamin D receptor (VDR) in nucleus • Increase in calbindin (Ca-binding protein)

13. Vitamin D Affects Absorption of Dietary Phosphorus • 1,25-(OH)2 D3 increases activity of alkaline phosphatase • Hydrolyses phosphate ester bonds • Releases phosphorus • Increase in phosphate carriers

14. Vitamin D deficiency

15. Etiology • 1. Lack of sunshine due to: • 1) Lack of outdoor activities • 2) Lack of ultraviolet light in fall and winter • 3) Too much cloud, dust vapour and smoke

16. Etiology • 2. Improper feeding: • 1) Inadequate intake of Vitamin D • Breast milk 0-10IU/100ml • Cow’s milk 0.3-4IU/100ml • Egg yolk 25IU/average yolk • Herring 1500IU/100g • 2) Improper Calcium and Phosphate ratio

17. Etiology • 3. Fast growth, increased requirement • Relative deficiency • 4. Diseases and drug: • Liver diseases, renal diseases • Gastrointestinal diseases • Antiepileptic • Glucocorticosteroid

18. GROUPS AT RISK • Infants • Elderly • Dark skinned • Covered women • Kidney failure patients • Patients with chronic liver disease • Fat malabsorption disorders • Genetic types of rickets • Patients on anticonvulsant drugs

19. Vitamin D deficiency • Deficiency of vitamin D leads to: • Rickets in small children. • Osteomalacia • Osteoporosis

20. Parathyroid Hormone (PTH) • Calcium-sensor protein in the thyroid gland • Detects low plasma calcium concentrations • Effects of parathyroid hormone • Urine / kidneys • Increases calcium reabsorption • Increases phosphorus excretion • Stimulates 1-hydroxylase activity in the kidneys • 25-OH D  1,25-(OH)2 D • PTH required for resorption of Ca from bone • Activates a calcium pump on the osteocytic membrane • Activates osteoclasts

21. Pathogenesis • Vitamin D deficiency • Absorption of Ca, P • Serum Ca • Increase Parathyroid Hormone

22. Pathogenesis • PTH • High secretion • Phosphate in urine Decalcification of old bone • S.Phosphate decrease S.Calcium normal or low slightly • Bone Mineralization Affected Rickets

23. Pathogenesis • Low secretion of PTH • Failure of decalcification of bone • Low serum Ca level • Rachitic tetany

24. Clinical manifestation • Rickets is a systematic disease with skeletons involved most, but the nervous system, muscular system and other system are also involved.

25. Clinical manifestation • Early stage • Usually begin at 3 months old • Symptoms: mental psychiatric symptoms • Irritability, sleepless • Laboratory findings: • Serum Ca, P normal or decreased slightly • ALP normal or elevated slightly • 25(OH)D3 decreased

26. Clinical manifestation • 4) Spinal column: scoliosis,kyphosis, and • lordosis • 5) Extremities: bowlegs,or knock knee, • greenstick fracture • 6) Rachitic dwarfism • 2. Muscular system: potbelly, late in standing and walking • 3. Motor development: delayed • 4. Other nervous and mental symptoms

27. Clinical manifestation • Advanced stage • On the base of early rickets, osseous changes become marked and motor development becomes delayed. • 1. Osseous changes: • 1) Head: frontal bossing, boxlike appearance of skull, delayed closure of anterior fontanelle • 2) Teeth: delayed eruption, with abnormal order, defects • 3) Chest: rachitic rosary, Harrison’s groove, pigeon chest, funnel-shaped chest

30. Clinical manifestation • Laboratory findings: Serum Ca and P decreased • Ca and P product decreased • AKP elevated • Late appearance of ossification center • Widening of the epiphyseal cartilage • Blurring of the preparatory calcification line • metaphyses like a cup • thinned cortex of the shaft of long bone

31. Rachitic vs. normal chick Rickets due to deficiency of vitamin D, Ca, or P

34. Vitamin D Deficiency - Rickets

35. Rickets in wrist - uncalcified lower ends of bones are porous and saucer-shaped (A) Rickets in 3 month old infant A (B) Healing after 28 days of treatment (C) After 41 days of treatment B C

40. Approved for: 1 Rickets

41. Diagnosis • Assessed according to the followings: • 1. History • 2. Physical examination • 3. Laboratory findings • 4. Roentgenographic changes

42. Differential diagnosis • 1. Hypophosphatemic Vitamin D resistant rickets • 2. Rickets of Vitamin D dependency • 3. Distal renal tubular acidosis • 4. Cretinism • 5. Chondrodystrophy

44. Treatment • 1. Food and nursing care • 2. Prevention of complications • 3. Special therapy • 1) Vitamin D therapy • A. General method • Vitamin D 2000-4000IU/day for 2-4 weeks, then change to preventive dosage (400IU). • B. A single large dose: For severe case, or Rickets with complication, or those who can’t bear oral therapy. Vitamin D3 200000-300000IU, im, preventive dosage will be used after 2-3 months.

45. Treatment • 2) Calcium supplementation: • only used for special cases, such as baby fed mainly with cereal, or infants under 3 months of age, and those who have already developed tetany. Dosage:1-3 g/day. • 3) Plastic therapy: In children with bone deformities after 4 years old plastic surgery may be useful.

46. Prevention • 1. Pay much attention to the health care of pregnant and lactating women, instruct them to take adequate amount of vitamin D. • 2. Advocate sunbathing • 3.Advocate breast feeding, give supplementary food on time

47. Prevention • 4. Vitamin D supplementation: In prematures, twins and weak babies, give Vitamin D 800IU per day, For term babies and infants the demand of Vitamin D is 400IU per day, For those babies who can’t maintain a daily supplementation, inject muscularly Vitamin D3 10000-200000 IU.

48. Prevention • 5. Calcium supplementation: 0.5-1gm/day, for premature, weak babies and babies fed mainly with cereal

49. Sources of Vitamin D • Sunlight is the most important source • Fish liver oil • Fish & sea food (herring & salmon) • Eggs • Plants do not contain vitamin D3

50. Vitamin D - Sources • Not found naturally in many foods • Synthesized in body • Plants (ergosterol) • Sun-cured forages • Fluid milk products are fortified with vitamin D • Oily fish • Egg yolk • Butter • Liver • Difficult for vegetarians