佝偻病手足抽搐症 ppt课件

Rickets of Vitamin D DeficiencyRickets of Vitamin D Deficiency Peng Jing Xiangya Hospital, CSU 2010. 11 Background What happened to these children ? First thorough account of rickets Francis Glisson(1650)Francis Glisson(1650) Martins e Silva J. Acta Reumatol Port,2007. 32:205.Martins e Silva J. Acta Reumatol Port,2007. 32:205. Mellanby Edward(1918) Isolation of the antiricketic factor from liver oil MellanbyMellanby E. E. Br Med J, Br Med J, 1924 1924 , 24: 895, 24: 895 Adolf windaus (1922) Synthetically prepare vitamin D3 “ no more campaign on rickets” In the 1970s VeenaVeena BahlBahl. Nutrition & Food Science, 1993, 81 :2. Nutrition & Food Science, 1993, 81 :2 Rowe PM. LancetRowe PM. Lancet, ,20012001, ,357:1100357:1100 In the 2000s “ “I think this is a I think this is a major major unrecognized epidemicunrecognized epidemic in in the United States. It affects the United States. It affects children and adults of all children and adults of all ages, all races, and both ages, all races, and both sexes. Its very significant. ”sexes. Its very significant. ” “Vitamin D deficiency “Vitamin D deficiency symptoms in children symptoms in children have have long been overlookedlong been overlooked.” .” The Lancet: “re-emergence of rickets” Rickets of vitamin D deficiency 营养性维生素D缺乏性佝偻病 To be familiar with its pathology, diagnosis To be familiar with its pathology, diagnosis and differential diagnosisand differential diagnosis Teaching aims To master its etiology,clinical manifestations, To master its etiology,clinical manifestations, treatment and prevention of Ricketstreatment and prevention of Rickets Definition What is Rickets? Mineralization:矿化 Osteoid:骨样组织 Osteomalacia:骨软化症 Rickets is the term signifying a failure in mineralization of growing bone or osteoid tissue due to deficiency of vitamin D The source and conversion of Vitamin D Resource of VitD Calciferol (vitD2) Cholecalciferol (vitD3) 7-dehydrocholesterol in skin 296310nm Materno-fetus Dietary and therapeutic source Activation of VitD VitD2 VitD3 25(OH)D3 1,25(OH)2D3 DBP Hydrooxylated in the renal Hydrooxylated in the Liver Circulating form Biologically active form Function of 1,25(OH)2D3 Facilitation of intestinal Facilitation of intestinal absorption of calcium and absorption of calcium and phosphorusphosphorus Reabsorption of phosphorus in the kidneys Direct effect on mineral metabolism of bone Accommodation of cell proliferation and immune system Receptors（intestins, renal, bone） Function of 1,25(OH)2D Quiz Tell us the function of 1,25(OH)2D3. What is the biologically active form of vitamin D? 25(OH) D3 What is the major circulating form of vitamin D ? 1,25(OH)2D3 Antiricketic function：intestines, renal, bone Others：anticancer，immunomodulation Etiology etiology Disease Inadequate intake Rapid growth Inadequate exposure in sunlight VitD deficiency during perinatal period children VitD deficiency during perinatal period Whether all pregnancies should be given vitamin D need for a large placebo-controlled double-blind trial. (Cochrane collaboration) etiology Diseases Inadequate intake Rapid growth Inadequate exposure in sunlight VitD deficiency during perinatal period children Seasons RegionsSkin colourslatitudes Inadequate exposure in sunlight Spring Autum City Countryside Black Asian White Higher Lower etiology Disease Inadequate intake Rapid growth Inadequate exposure in sunlight VitD deficiency during perinatal period children Rapid growth Multiple SinglePremature Full term etiology Diseases Inadequate intake Rapid growth Inadequate exposure in sunlight VitD deficiency during perinatal period children Supply calcium without VitD Delay auxiliary foods (辅食) Milk：25 IU/1L Yolk：98IU/1g Calcium deficiency = Vitamin D deficiency Inadequate intake of Vit D etiology Diseases Inadequate intake Rapid growth Inadequate exposure in sunlight VitD deficiency during perinatal period children Antiseizure therapy抗癫痫治疗 phenobarbital Celiac disease Cystic disease胆道疾病 胃肠道疾病 苯巴比妥 Disease (chronic gastrointestinal diseases/ hepatic disease / renal disease) Quiz What is the major cause of rickets ? Inadequate exposure in sunlight Pathology 骨的进一步生长 软骨储备区 软骨增生区 软骨钙化区 成骨区 q 骺软骨不断生长并被骨组织替换。 CalcifyCa*P 40 钙盐沉着 3y Osseous changes + hypotonic + neural syndrome 早期激期 恢复期 后遗症期 1. Neurologic symptoms （sweating and irritation） 2. No osseous changes（骨骼无异常） 1. craniotabes (颅骨软化) 3. Serum calcium and phosphorus , 25(OH)VitD PTH AKP 4. X ray is normal Early stage( 1yr） Bowlegs (“O” 型腿)Knock-knees (“X”型腿) hypotony Crookback （驼背）Frog belly (蛙腹) 2010. 11 Question 4: How to confirm the diagnosis Biochemistry Labs Calcium :2 (2.25 2.75mmol/L ) Phosphorus : 1 (1.3 2.3mmol/L) CaP: 35 (35 45mg/dL) PTH : 10 （110pmol/L） AKP: 240（50240U /L) Golden standard: Serum 25-(OH)D3 level is decreased(20ng/mL)* X ray changes Biochemist ry Calcium and phosphorus AKP PTH 25(OH)VitD Alteratio n of bones Radiograp hy Neurolog ic symptom s Craniotabes Pigeon breast Bowlegs and knock-knees Cephalus quadratus Rachitic Osteoporosis Temporary calcification line extinction Osteoid tissue stacking Epiphyseal ribbon broader Summary Sweating Irritation Healing rickets( 6m-2y ) 1. Clinical manifestations become invisible 2. Serum biochemistry exams are becoming normal. 3. X rays are becoming normal 58 Sequela stage( 3y ) 1. No clinical manifestations 2. Normal serum Ca, P and AKP 3. Normal X ray 4. Skeletal deformities 59 Quiz What are major clinical features of Rickets of VitD deficiency? 分期 初期 激期 恢复期 后遗症期 神经 肌肉 改变 夜啼 多汗 激惹 运动机能迟缓 肌张力低下 智力发育低下 好转 无 骨骼 改变 无 骨骼软化 骨样组织堆积 好转 畸形 生化 检查 X线 PTH Ca P AKP 25(OH)D (-) PTH Ca P AKP 25(OH)D (+) 好转 好转 正常 正常 佝偻病各期临床表现 61 Diagnosis laboratory Radiographic exam Serum levels of calcium and phosphorus Elevated PTH and AKP Urinalysis, renal and liver function 。 Prematurity Medical history (gestational age, diet, degree of sunlight exposure, family history, disease) Physical examination clinical Diagnosis Serum 25-(OH)D level is decreased(20ng/mL)* Differential diagnosis 64 Differential diagnosis Rickets of anti VitD (抗维生素D佝偻病) 1. X-linked hypophosphatemic rickets(低血磷性抗维生素D 佝偻病) 2. renal tubule acidosis (远端肾小管性酸中毒) 3. vitamin D-dependent rickets (VitD依赖性佝偻病) 4. renal rickets (肾性佝偻病) 5. liver rickets (肝性佝偻病)strongly s/o recent Asphyxia Mucopolysaccharidosis (粘多糖病) achondroplasia (软骨发育不全) Hydrocephalus (脑积水) s/o recent Asphyxia 65 粘多糖病 鉴别诊断 66 软骨发育不良 鉴别诊断 67 脑积水 68 Treatment Treatment sunlight exposure vitamin Dvitamin D Calcium objective: Control disease and prevent bone deformity. 1. Natural and artificial sunlight exposure 2. Oral administration of VitD 1. VitD2 2000-4000 IU/d 2-4w 400IU/d 2. calcifediol(2g/kg.d) calcitriol (0.05 0.2g/kg.d) 3. Intramuscle injection of VitD2/3 VitD 30-60万IU 1-3 times 4. Calcium 0.5-1.0g/d, 30 to 75 mg/kg.d (hungry bone) 71 Monitoring After treatment initiation, all patients will required careful monitoring. 1. Serum ca, p and AKP, urinary ca/creatinine ratio and kidney function should be measure 4 weeks after the start of therapy. These tests should be repeated after 3 months. 2. A rise in the level of phosphorus followed by calcium 3. Reappearance of urinary calcium excretion 2. Radiograhs should be obtained after 3 months of therapy. If the radiographs do not show evidence of healing, the possibility of poor adherence to treatment, malabsorption, or of other forms of rickets should be considered. 72 Prevention 1. Breast feeding 2. Ensure adequate exposure to sunlight 3. Vitamin D supplementation is recommended 400IU/d Premature neonate、multiple fetals、low birth weight infants：1 week after birth 800IU/d*3 mon400 IU/d Full term neonate：2weeks after birth 400IU/d*2 years old 4. VitD for pregnant women 73 The American Academy of pediatrics(AAP) all breastfed infant and bottlefed infants (receiving less than 500ml formula daily) should receive 200 IU vitamin D daily. 74 Tetany of vitamin D deficiency 维生素D缺乏性手足搐搦症 75 General consideration 76 General consideration Tetany of vitamin D deficiency occurs most frequently under the ages of 6 month. Tetany is rare today owing to widespread prophylactic use of vitamin D. Tetany is occasionally associated with celiac disease, such as diarrhea. 77 Definition VitD deficiency causes hypocalcemia directly increases peripheral neuromuscular irritability, which can cause convulsion or local muscle tic 78 Pathology 79 结合钙-Constructing of bone 99% 游离钙 -Accommadation in cell excretion, signal entrainment, stimulated nerve muscle convection, blood clotting, and blood oxygen traffic Biologic function of Ca 80 Serum Ca Accommodation of Ca l 1,25（OH）2D3、PTH、CT PH Plasma protein concentration Plasma phosphorus concentration The compose of Serum Ca (1%) ionic Ca （47%）: physioactivity protein binding Ca （47%）: unactivity compound （6%）: binding with organic acid and inorganic acid,unactivity 81 hypocalcemia Deficiency of VitD Less calcium is absorbed from the intestine hypocalcemia Parathormone （PTH） 100 No serum Ca P* Mobilization of calcium and phosphorus from the bone kidney Decrease ph reabsorption Maintain the serum calcium level rickets tetany A failure in mineralization of growing bone or osteoid tissue Mechanism 82 Clinical manifestations 83 Clinical manifestations Latent