1、,Rickets of Vitamin D Deficiency,Peng JingXiangya Hospital, CSU,2010. 11,Background,What happened to these children ?,First thorough account of rickets,Francis Glisson(1650),Martins e Silva J. Acta Reumatol Port,2007. 32:205.,Mellanby Edward(1918),Isolation of the antiricketic factor from liver oil,
2、Mellanby E. Br Med J, 1924 , 24: 895,Adolf windaus (1922),Synthetically prepare vitamin D3,“ no more campaign on rickets”,In the 1970s,Veena Bahl. Nutrition & Food Science, 1993, 81 :2,Rowe PM. Lancet,2001,357:1100,In the 2000s,“I think this is a major unrecognized epidemic in the United States. It
3、affects children and adults of all ages, all races, and both sexes. Its very significant. ” “Vitamin D deficiency symptoms in children have long 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 and diffe
4、rential diagnosis,Teaching aims,To master its etiology,clinical manifestations, treatment and prevention of Rickets,Definition,What is Rickets?,Mineralization:矿化 Osteoid:骨样组织 Osteomalacia:骨软化症,The source and conversion of Vitamin D,Resource of VitD,Calciferol (vitD2),Cholecalciferol (vitD3),7-dehydr
5、ocholesterol 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 absorption of calcium
6、and phosphorus,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 vitami
7、n 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,VitD deficien
8、cy 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,Inadequate exposure i
9、n sunlight,etiology,Disease,Inadequate intake,Rapid growth,Inadequate exposure in sunlight,VitD deficiency during perinatal period,Rapid growth,etiology,Diseases,Inadequate intake,Rapid growth,Inadequate exposure in sunlight,VitD deficiency during perinatal period,Supply calcium without VitD,Delay a
10、uxiliary 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,Antiseizure therapy,抗癫痫治疗,phenobarbital,Celiac disease,Cystic d
11、isease,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,骺软骨不断生长并被骨组织替换。,Calcify,Ca*P, 40 钙盐沉着, 35 旧骨脱钙,钙磷的作用,34,Decreased serum calcium level,Deficiency of VitDLess
12、 calcium is absorbedfrom the intestine,Hypocalcemic,Parathormone （PTH）,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,甲状旁腺素 （PTH）,3
13、5,osteoporosis occurs（骨膜增厚，骨质疏松软化）temporary calcification line lost normal shape or extinction （临时钙化带失去正常形态或消失） Osteoid tissue stacking（骨样组织堆积）Epiphyseal ribbon broader （干骺端变宽）,Parathyriod glands 甲状旁腺,Quiz,Calcium deficiency=Vitamin D deficiency,?,Quiz,Clinical manifestations,Could you help us, doct
14、or?,Case report,8-month-old female child Exclusively breast-fed without vitamin supplement The mother did not receive any vitamins or calcium Presented with irritation and night sweating for 4 months Physical examination showed pulvinar bald(枕秃), cephalus quadratus（方颅）, without primary teeth erupion
15、. Clinical diagnosis ?,Rickets of vitamin D deficiency,Summary,Early stage,Active rickets,Healing rickets,Sequela stage, 6m,6m-2y,6m-2y, 3y,Osseous changes + hypotonic + neural syndrome,早期,激期,恢复期,后遗症期,42,Neurologic symptoms （sweating and irritation） 2. No osseous changes（骨骼无异常）craniotabes (颅骨软化) 3.
16、Serum calcium and phosphorus , 25(OH)VitD PTH AKP 4. X ray is normal,Early stage( 6m ),Question 1 Why？,Sweating Irritation,Irritation Bone pain,vitDdeficiency,Mechanism,低钙血症,神经、肌肉兴奋性增高,激惹、骨痛,Question 2 Why is that?,46,Neurologic symptoms （sweating and irritation） 2. No osseous changes（骨骼无异常）craniota
17、bes (颅骨软化) 3. Serum calcium and phosphorus , 25(OH)VitD PTH AKP 4. X ray is normal,Early stage( 6m ),Question 3: If in progress?,If not recognized and properly treated, vitamin D deficiency may cause pain, fractures, skeletal deformity, growth retardation, dental defects, delayed developmental miles
18、tones and, in severe cases, hypocalcemic tetany and seizures.,Alteration of bones,craniotabes pigeon breast bowlegs and knock-knees cephalus quadratus rachitic,48,Active rickets( 6m-2y ),Increasing neural symptoms Typical alteration of bone(s) 3. changes of muscle tone 4. Serum calcium and phosphoru
19、s AKP 25(OH)VitD PTH 5. X ray is abnormal,49,Prematurity craniotabes pigeon breast harrison groove “X”form leg、“O” form leg,rachitic rosary cephalus quadratus rachitic,Osteomalacia,Osteoid staking,alteration of bone,Skull (头颅,16moths),Thorax（胸部,612months）,Extremity（四肢,1yr）,hypotony,2010. 11,Question
20、 4: How to confirm the diagnosis,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,Calcium and phosphorus AKP PTH 25(OH)VitD,Alteration of bones,Su
21、mmary,Sweating Irritation,58,Healing rickets( 6m-2y ),1. Clinical manifestations become invisible 2. Serum biochemistry exams are becoming normal. 3. X rays are becoming normal,59,Sequela stage( 3y ),1. No clinical manifestations 2. Normal serum Ca, P and AKP 3. Normal X ray 4. Skeletal deformities,
22、Quiz,What are major clinical features ofRickets of VitD deficiency?,61,佝偻病各期临床表现,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,
23、family history, disease) Physical examination,clinical,Diagnosis,Serum 25-(OH)D level is decreased(20ng/mL)*,64,Differential diagnosis,65,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-depend
24、ent 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,66,粘多糖病,鉴别诊断,67,软骨发育不良,鉴别诊断,68,脑积水,Treatment,Treatment,vitamin D,Calcium,71,objective:Control disease an
25、d prevent bone deformity.,Natural and artificial sunlight exposure 2. Oral administration of VitD VitD2 2000-4000 IU/d 2-4w 400IU/d 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),72,Mo
26、nitoringAfter treatment initiation, all patients will required careful monitoring.,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. A rise in the level of phosphorus followed by c
27、alcium 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.,73,Prevention,Breast feed
28、ingEnsure adequate exposure to sunlightVitamin 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,74,The American Academy of p
29、ediatrics(AAP),all breastfed infant and bottlefed infants (receiving less than 500ml formula daily) should receive 200 IU vitamin D daily.,75,Tetany of vitamin D deficiency维生素D缺乏性手足搐搦症,76,General consideration,77,General consideration,Tetany of vitamin D deficiency occurs most frequently under the a
30、ges 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.,78,Definition,VitD deficiency causes hypocalcemia directly increases peripheral neuromuscular irritability, which can cause convulsion or l
31、ocal muscle tic,79,Pathology,80,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,81,Serum Ca,Accommodation of Ca l 1,25（OH）2D3、PTH、CTPH Plasma protein concentrati
32、onPlasma phosphorus concentration,The compose of Serum Ca (1%)ionic Ca （47%）: physioactivityprotein binding Ca （47%）: unactivity compound （6%）: binding with organic acid and inorganic acid,unactivity,82,hypocalcemia,Deficiency of VitDLess calcium is absorbedfrom the intestine,hypocalcemia,Parathormo
33、ne （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,83,Clinical manifestations,84,Clinical manifestations,Latent tetany
34、 No symptoms Positive signs Chvostek Trousseau Peroneal reflex serum calcium lever is less than 1.75-1.88mmol/L,Manifest tetany Laryngospasm Carpopedal spasm Convulsions Serum calcium lever is is often well under 1.75mmol/L,85,Figure: Carpopedal spasm,86,diagnosis,87,diagnosis,History- age, season,
35、history of VD dificiency, symptoms and signs of rickets,Clinical manifestations - convulsion without fever, repeat occurs, consciouse after seizures without CNS signs,Total Ca - 1.75-1.88mmol/L, ionic Ca1.0mmol/L。,88,Differential diagnosis,Convulsion without fever hypomagnesemia Hypoparathyroidism H
36、ypoglycemia Infantile spasms,otherscentral never system infectiousacute laryngitis,89,Case 1,病例分析：假设同学们在急诊室值班，一个6个月的婴儿，因为抽搐急诊入院，请问你如何进行抽搐查因的分析？如何进行诊治。 （5分钟分组讨论，5分钟陈述观点）,90,Treatment,91,treatment,Emergency treatment Basic life support (establish airway, oxygen inhalation and mechanical ventilation) Anticonvulsant and control laryngospasm Calcium supplementation Others : Administration of VitD,
