2. Vitamin D Deficiency Rickets
Fan Yang
Associated Professor
Pediatric Department

3. Vitamin D Vitamin D comprises a group of sterols
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 from the 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.

6. Vitamin D: The Sunshine Vitamin
Not always essential
Body can make it if exposed to enough sunlight
Made from cholesterol in the skin

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

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

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

12. Vitamin D Functions

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

14. 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

15. Vitamin D deficiency

16. 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

17. Etiology 2. Improper feeding: 1) Inadequate intake of Vitamin D
Breast milk IU/100ml
Cow’s milk IU/100ml
Egg yolk IU/average yolk
Herring IU/100g
2) Improper Ca and P ratio

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

19. 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

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

21. 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

22. Pathogenesis Vitamin D deficiency Absorption of Ca, P Serum Ca
Function of Parathyroid

23. Pathogenesis PTH High secretion P in urine Decalcification of old bone
P in blood Ca in blood normal or low slightly
Ca, P product
Rickets

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

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

26. Clinical manifestation
Early stage
Usually begin at 3 months old
Symptoms: mental psychiatric symptoms
Irritability, sleepless, hidrosis
Signs: occipital bald
Laboratory findings: Serum Ca, P normal or
decreased slightly, AKP normal or elevated slightly,25(OH)D3 decreased
Roentgenographic changes: normal or change slightly

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: craniotables, 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, flaring of ribs

28. 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

29. Clinical manifestation
Laboratory findings: Serum Ca and P decreased
Ca and P product decreased
AKP elevated
Roentgenographic changes: Wrist is the best site for
watching the changes.
Late appearance of ossification center
Widening of the epiphyseal cartilage
Blurring of the preparatory calcification line
metaphyses like a cup
rarefaction of the bone
thinned cortex of the shaft of long bone

30. Clinical manifestation
Healing stage:
Symptoms and signs of Rickets alleviate or disappear by use of appropriate treatment. The blood chemistries become normal, except AKP may be slightly elevated.
Sequelae stage:
All the clinical symptoms and signs disappear. Blood Chemistries and X-ray changes are recovered, but osseous deformities may be left. Usually seen in Children after 3 years old.

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

34. Vitamin D Deficiency - Rickets

35. A B C (B) Healing after 28 days of treatment
Rickets in wrist - uncalcified lower ends of bones are porous, ragged, 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 2. Prevention of complications 3. Special therapy
1. Food and nursing care
2. Prevention of complications
3. Special therapy
1) Vitamin D therapy
A. General method
Vitamin D IU/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 D IU, 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 D 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

51. TOXICITY Hypervitaminosis D causes hypercalcemia, which manifest as:
Nausea & vomiting
Excessive thirst & polyuria
Severe itching
Joint & muscle pains
Disorientation & coma.

52. Vitamin D Toxicity Calcification of soft tissue Hypercalcemia
Lungs, heart, blood vessels
Hardening of arteries (calcification)
Hypercalcemia
Normal is ~ 10 mg/dl
Excess blood calcium leads to stone formation in kidneys
Lack of appetite
Excessive thirst and urination
Infants:

53. Thank You！