2 Vitamin D Deficiency Rickets Fan YangAssociated ProfessorPediatric Department
3 Vitamin D Vitamin D comprises a group of sterols Vitamin D2 = ergocalciferolCompletely synthetic form produced by the irradiation of the plant steroid ergosterolVitamin D3 = cholecalciferolProduced photochemically by the action of sunlight or ultraviolet light from the precursor sterol 7-dehydrocholesterolVitamin D = calciferol
4 VITAMIN DHumans & 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 DExposure 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 essentialBody can make it if exposed to enough sunlightMade from cholesterol in the skin
8 Formation of Vitamin D Skin (UV light) 7-dehydro cholesterol Vitamin D3Ergosterol Vitamin D2LiverOH-group added25-Hydroxy vitamin D3Storage form of vitamin (~3 months storage in liver)KidneyOH-group added by 1-hydroxylase1,25-dihydroxy vitamin D3Active form of vitamin D, a “steroid hormone”OH-group added by 24-hydroxylase24,25-dihydroxy vitamin D3Inactive form of vitamin D, ready for excretion
10 FUNCTIONSCalcium metabolism: vitamin D enhances ca absorption in the gut & renal tubules.Cell differentiation: particularly of collagen & skin epitheliumImmunity: 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 levelsPhosphorus absorption (small intestine)HormoneRegulation of gene expressionCell growth
16 Etiology 1. Lack of sunshine due to: 1) Lack of outdoor activities 2) Lack of ultraviolet light in fall and winter3) Too much cloud, dust vapour and smoke
17 Etiology 2. Improper feeding: 1) Inadequate intake of Vitamin D Breast milk IU/100mlCow’s milk IU/100mlEgg yolk IU/average yolkHerring IU/100g2) Improper Ca and P ratio
18 Etiology 3. Fast growth, increased requirement Relative deficiency 4. Diseases and drug:Liver diseases, renal diseasesGastrointestinal diseasesAntiepilepticGlucocorticosteroid
19 GROUPS AT RISK Infants Elderly Dark skinned Covered women Kidney failure patientsPatients with chronic liver diseaseFat malabsorption disordersGenetic types of ricketsPatients on anticonvulsant drugs
20 Vitamin D deficiency Deficiency of vitamin D leads to: Rickets in small children.OsteomalaciaOsteoporosis
21 Parathyroid Hormone (PTH) Calcium-sensor protein in the thyroid glandDetects low plasma calcium concentrationsEffects of parathyroid hormoneUrine / kidneysIncreases calcium reabsorptionIncreases phosphorus excretionStimulates 1-hydroxylase activity in the kidneys25-OH D 1,25-(OH)2 DPTH required for resorption of Ca from boneActivates a calcium pump on the osteocytic membraneActivates 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 slightlyCa, P productRickets
24 Pathogenesis Low secretion of PTH Failure of decalcification of bone Low serum Ca levelRachitic 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 stageUsually begin at 3 months oldSymptoms: mental psychiatric symptomsIrritability, sleepless, hidrosisSigns: occipital baldLaboratory findings: Serum Ca, P normal ordecreased slightly, AKP normal or elevated slightly,25(OH)D3 decreasedRoentgenographic changes: normal or change slightly
27 Clinical manifestation Advanced stageOn 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 fontanelle2) Teeth: delayed eruption, with abnormal order, defects3) Chest: rachitic rosary, Harrison’s groove, pigeon chest, funnel-shaped chest, flaring of ribs
28 Clinical manifestation 4) Spinal column: scoliosis,kyphosis, andlordosis5) 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
29 Clinical manifestation Laboratory findings: Serum Ca and P decreasedCa and P product decreasedAKP elevatedRoentgenographic changes: Wrist is the best site forwatching the changes.Late appearance of ossification centerWidening of the epiphyseal cartilageBlurring of the preparatory calcification linemetaphyses like a cuprarefaction of the bonethinned 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
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 infantA(B) Healing after 28 days of treatment(C) After 41 days of treatmentBC
44 Treatment 2. Prevention of complications 3. Special therapy 1. Food and nursing care2. Prevention of complications3. Special therapy1) Vitamin D therapyA. General methodVitamin 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 Prevention1. 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
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 oilFish & sea food (herring & salmon)EggsPlants do not contain vitamin D3
50 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
52 Vitamin D Toxicity Calcification of soft tissue Hypercalcemia Lungs, heart, blood vesselsHardening of arteries (calcification)HypercalcemiaNormal is ~ 10 mg/dlExcess blood calcium leads to stone formation in kidneysLack of appetiteExcessive thirst and urinationInfants: