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Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Mar 31, 2015

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Page 1: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 2: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D Deficiency Rickets

Fan Yang

Associated Professor

Pediatric Department

Page 3: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D

Vitamin D comprises a group of sterolsVitamin D2 = ergocalciferol

Completely synthetic form produced by the irradiation of the plant steroid ergosterol

Vitamin D3 = cholecalciferolProduced photochemically by the action of

sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterol

Vitamin D = calciferol

Page 4: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

VITAMIN DVITAMIN 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.

Page 5: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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.

Page 6: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D: The Sunshine Vitamin

Not always essentialBody can make it if

exposed to enough sunlight

Made from cholesterol in the skin

Page 7: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 8: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Formation of Vitamin D

Skin (UV light)7-dehydro cholesterol Vitamin D3

Ergosterol Vitamin D2

LiverOH-group added

25-Hydroxy vitamin D3 Storage form of vitamin (~3 months storage in liver)

KidneyOH-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

Page 9: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 10: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

FUNCTIONSFUNCTIONS

•Calcium metabolismCalcium metabolism: vitamin D enhances ca absorption in the gut & renal tubules.•Cell differentiationCell differentiation: particularly of collagen & skin epithelium

•ImmunityImmunity: important for Cell Mediated Immunity & coordination of the immune response.

Page 11: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D - Functions

Bone developmentCalcium absorption (small intestine)Calcium resorption (bone and kidney)Maintain blood calcium levelsPhosphorus absorption (small intestine)

HormoneRegulation of gene expressionCell growth

Page 12: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D Functions

Page 13: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Groff & Gropper, 2000

Vitamin D Affects Absorption of Dietary Ca

1,25-(OH)2 D binds to vitamin D receptor (VDR) in nucleus

Increase in calbindin (Ca-binding protein)

Page 14: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D Affects Absorption of Dietary Phosphorus

1,25-(OH)2 D3 increases activity of alkaline phosphataseHydrolyses phosphate ester bonds

Releases phosphorus

Increase in phosphate carriers

Page 15: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D deficiencyVitamin D deficiency

Page 16: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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

Page 17: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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 Ca and P ratio

Page 18: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Etiology

3. Fast growth, increased requirement Relative deficiency4. Diseases and drug: Liver diseases, renal diseases Gastrointestinal diseases Antiepileptic Glucocorticosteroid

Page 19: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

GROUPS AT RISKGROUPS 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

Page 20: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D deficiencyVitamin D deficiency

•Deficiency of vitamin D leads to:Deficiency of vitamin D leads to:

Rickets in small children.

Osteomalacia

Osteoporosis

Page 21: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Parathyroid Hormone (PTH)

Calcium-sensor protein in the thyroid glandDetects low plasma calcium concentrations

Effects of parathyroid hormoneUrine / kidneys

Increases calcium reabsorptionIncreases phosphorus excretion

Stimulates 1-hydroxylase activity in the kidneys25-OH D 1,25-(OH)2 D

PTH required for resorption of Ca from boneActivates a calcium pump on the osteocytic

membraneActivates osteoclasts

Page 22: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Pathogenesis

Vitamin D deficiency

Absorption of Ca, P

Serum Ca

Function of Parathyroid

Page 23: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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

Page 24: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Pathogenesis

Low secretion of PTH

Failure of decalcification of bone

Low serum Ca level

Rachitic tetany

Page 25: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Clinical manifestation

Rickets is a systematic disease with

skeletons involved most, but the

nervous system, muscular system and

other system are also involved.

Page 26: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Clinical manifestation

Early stageUsually begin at 3 months oldSymptoms: mental psychiatric symptoms Irritability, sleepless, hidrosisSigns: occipital baldLaboratory findings: Serum Ca, P normal or

decreased slightly, AKP normal or elevated slightly,25(OH)D3 decreased

Roentgenographic changes: normal or change slightly

Page 27: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Clinical manifestationAdvanced 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

Page 28: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Clinical manifestation

4) Spinal column: scoliosis,kyphosis, and lordosis5) Extremities: bowlegs,or knock knee, greenstick fracture6) Rachitic dwarfism2. Muscular system: potbelly, late in standing

and walking3. Motor development: delayed4. Other nervous and mental symptoms

Page 29: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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

Page 30: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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.

Page 31: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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

Page 32: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 33: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 34: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D Deficiency - Rickets

Page 35: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Rickets in wrist - uncalcified lower ends of bones are porous, ragged, and saucer-shaped

(A) Rickets in 3 month old infant

(B) Healing after 28 days of treatment

(C) After 41 days of treatment

A

B C

Page 36: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 37: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 38: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 39: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

                                     

Page 40: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 41: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Diagnosis

Assessed according to the followings:1. History2. Physical examination3. Laboratory findings4. Roentgenographic changes

Page 42: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Differential diagnosis

1. Hypophosphatemic Vitamin D resistant rickets

2. Rickets of Vitamin D dependency3. Distal renal tubular acidosis4. Cretinism5. Chondrodystrophy

Page 43: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.
Page 44: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Treatment 1. Food and nursing care2. Prevention of complications3. 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.

Page 45: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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.

Page 46: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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 sunbathing3.Advocate breast feeding, give

supplementary food on time

Page 47: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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.

Page 48: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Prevention

5. Calcium supplementation:

0.5-1gm/day, for premature, weak babies

and babies fed mainly with cereal

Page 49: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Sources of Vitamin DSources of Vitamin D

Sunlight is the most important source

Fish liver oil

Fish & sea food (herring & salmon)

Eggs

Plants do not contain vitamin D3

Page 50: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D - Sources

Not found naturally in many foods

Synthesized in bodyPlants (ergosterol)

Sun-cured foragesFluid milk products are

fortified with vitamin DOily fishEgg yolkButterLiverDifficult for vegetarians

Page 51: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

TOXICITYTOXICITY•Hypervitaminosis DHypervitaminosis D

causes hypercalcemia, which manifest as:

Nausea & vomiting

Excessive thirst & polyuria

Severe itching

Joint & muscle pains

Disorientation & coma.

Page 52: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

Vitamin D Toxicity

Calcification of soft tissueLungs, heart, blood vessels Hardening of arteries (calcification)

Hypercalcemia Normal is ~ 10 mg/dlExcess blood calcium leads to stone formation

in kidneysLack of appetiteExcessive thirst and urination

Infants:

Page 53: Vitamin D Deficiency Rickets Fan Yang Associated Professor Pediatric Department.

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