佝偻病-终稿课件

ricketsofvitaminDdeficiency

（营养性维生素D缺乏性佝偻病）哈医大二院儿内科周萍问题1.儿歌？2.为什么北方人更容易患佝偻病？3.缺钙后，为何有的患佝偻病，有的手足搐溺？4.全民补钙对吗？5.佝偻病是缺钙还是缺D？教学大纲掌握：VD缺乏性佝偻病的病因、发病机制、临床表现、治疗和预防VD缺乏性佝偻病和手足搐搦症的发病机制区别熟悉：VD缺乏症佝偻病的鉴别诊断了解：VD的来源、转化VD的生理功能与调节

summarizeDefinition:Ricketsisaverycommonchronicnutritionaldeficientdisease

VitaminDdeficiencycauserickets,ametabolicdisorderofcalciumandphosphoruswithafailuretomineralizeosteoidtissueofgrowingboneresultinginbonydeformities.

生长着的长骨干骺端或骨组织矿化不全成熟骨矿化不全表现为骨质软化症

inyoungchildrenespeciallyundertwoyearsoldofage.

北方患病率高于南方VD的生理脂溶性类固醇衍生物分类：VD2（麦角骨化醇）--植物

VD3（胆骨化醇）--人和动物皮肤吸收：食物VD小肠刷状缘淋巴管吸收皮肤合成VD3

直接吸收入血转运与贮存：与血浆中VD结合蛋白（DBP）结合后被转运,贮存于肝脏、脂肪、肌肉等组织内VitaminDMetabolismandPhysiology

代谢与生理VitaminDisagenerictermforagroupofsteroids,themostimportantingredientsofwhicharecholecalciferol（vitaminD3）andergocalciferol(vitaminD2)维生素D是一类类固醇，最主要的是胆骨化醇（维生素D3）和麦角骨化醇（维生素D2）ThenaturalsourceofvitaminDforthehumanisthecholecalciferolproducedintheskinfollowingexposuretotheultravioletradiationofsunshine,whichactivatestheskin7-dehydrocholesterolVitaminDMetabolismandPhysiology维生素D促进小肠细胞吸收Ca骨由细胞和间质组成，间质中含有无机盐和有机质。骨盐的成分主要是钙与磷酸化合而成的羟化磷灰石。骨组织成分：间充质细胞成骨细胞骨细胞失去分泌功能分泌基质和胶原纤维骨样组织骨间质，骨组织钙离子沉积骨发生：【长骨发生】

软骨静止区软骨增生区软骨基质钙化区骨化区骨化区骨小梁成骨区软骨基质()成骨细胞()破骨细胞()钙磷乘积：儿童之所以患佝偻病，是因为维生素D缺乏时，钙磷乘积下降(<40)，使成熟软骨细胞及成骨细胞不能钙化而继续增殖，形成骨骺端骨样组织堆积，临时钙化带增厚，骨骼膨大，形成临床所见肋骨串珠、手镯、脚镯征等，颅骨骨样组织堆积造成方颅。儿童、成人、老人钙磷代谢表现异同

SunexposureMotherSourceofVitD

FoodSupporttwoweeksNaturalfoods:inadequateMajorsourceSourcesofVitaminD

SunlightisthemostimportantsourceFishliveroilFish&seafood(herring&salmon)EggsPlantsdonotcontainvitaminD3VitaminD–

SourcesNotfoundnaturallyinmanyfoodsSynthesizedinbodyPlants(ergosterol)Sun-curedforagesFluidmilkproductsarefortifiedwithvitaminDOilyfishEggyolkButterLiverDifficultforvegetariansNaturalfoodsBreastmilk1µg

/LCow’smilk0.5-1µg/LEgg1.75µg

/100gButter0.75-1.5µg

/100g*VitD1µg=40IUContentofVitD表1富含维生素D食物一览表(国际单位/100克)品名含量品名含量鱼肝油1.9万鸡肝60沙丁鱼1300猪肝45鲱鱼315牛肝26大比目鱼44奶油50鸡蛋55人乳18蛋黄400牛乳0.35VD代谢的调节自身反馈作用血钙磷浓度与甲状旁腺素(PTH)的调节血钙磷浓度与降钙素(CT)的调节

VitD2,3自身反馈自身反馈VD的自身反馈调节25-(OH)D31,25-(OH)2D3VD代谢的调节-PTH(parathormone)血磷血钙PTH肾1,25(OH)2D成骨细胞骨破骨细胞

血钙骨重吸收

低血钙VitD2,325-(OH)D3VitD的调节；血钙磷浓度+PTH低血磷1,25-(OH)2D3

VD代谢的调节-CT(calcitonin)血钙CT肾1,25(OH)2D血磷肾1,25(OH)2D1,25-(OH)2D3

VitD的调节高血钙VitD2,325-(OH)D3VitD的调节高血磷+CTVD的生理与DBP结合：85%血中1,25(OH)2D3与白蛋白结合：15%游离：0.4%对靶器官发挥生物效应肠肾骨VD的生理功能肠：促小肠粘膜细胞合成钙结合蛋白（CaBP）促进钙、磷从肠道吸收，促使骨钙沉积。肾：促进肾小管对钙、磷的重吸收，利于骨矿化。骨：促进成骨细胞的增殖和破骨细胞分化。与PTH、CT一起，对维持体液和组织的钙磷内环境起主要作用。Antirachiticfunction抗佝偻病作用1.Facilitationofintestinalabsorptionofcalciumandphosphorus促进小肠对钙和磷的吸收2.Directeffectonmineralmetabolismofbone(depositionandreabsorption)对骨的矿物质代谢有直接作用（沉积和重吸收）Antirachiticfunction抗佝偻病作用3.Inconjunctionwithparathormoneandcalcitonin与甲状旁腺素和降钙素相协同4.Amajorroleinhomeostasisofcalciumandphosphorusinthebody’sfluidsandtissues对体液和组织中钙和磷的平衡的调节起重要作用病因—掌握日照不足AbsenceofsunshineVD摄入不足Dietarydeficiency

生长速度快Rapidgrowth疾病影响Diseasefactors药物影响InfluenceofthedrugEtiology1.Lackofsunshinedueto:1)Lackofoutdooractivities2)Lackofultravioletlightinfallandwinter3)Toomuchcloud,dustvapourandsmokeEtiology

2.Improperfeeding:1)InadequateintakeofVitaminDBreastmilk0-10IU/100mlCow’smilk0.3-4IU/100mlEggyolk25IU/averageyolkHerring1500IU/100g2)ImproperCaandPratioEtiology

3.Fastgrowth,increasedrequirementRelativedeficiency4.Diseasesfactors:Liverdiseases,renaldiseasesGastrointestinaldiseasesEtiology

5.Drugfactors:Antiepileptic抗癫痫药Glucocorticosteroid糖皮质类固醇发病机制pathogenesis（掌握）：VitaminD-deficientricketscanbeconceptualizedtobethebody'sattempttomaintainnormalserumcalciumlevels.机体为维持血钙水平而对骨骼造成的损害VitD缺乏肠道吸收钙磷低血钙甲状旁腺PTH分泌破骨细胞作用骨重吸收血钙正常或偏低肾小管重吸收磷血磷钙磷乘积骨矿化受阻佝偻病血钙不能恢复正常手足搐搦PTH分泌发病机制（掌握）ClinicalManifestations

Thediseaseoccursmostcommonlyfromagesof3monthsto2years.Theprincipalmanifestationsarechangesofgrowingskeleton,weaknessandrelaxationofmuscles,andnonspecificneuropsychicsymptoms.主要表现为生长最快部位的骨骼改变、肌肉松弛及神经兴奋性改变Clinicalmanifestation-EarlystageUsuallybeginat3monthsoldSymptoms:mentalpsychiatricsymptomsIrritability,sleepless,hidrosis多汗Signs:occipitalbald枕秃NoobviousskeletalchangesXraychanges:normalorchangeslightlyClinicalmanifestation-EarlystageLaboratoryfindings:SerumCa,PnormalordecreasedslightlyAKPnormalorelevatedslightly25(OH)D3decreasedCanormal,PnormalorAKP

25-(OH)D3↓,PTH↑EarlystageTheearlymanifestationsinricketsincludeirritability,restlessness,suddencryingatnight,alopeciainocciput,andincreasedsweatingparticularlyaroundtheheadwhichisirrelativewithroomtemperatureandseasons.初期，表现为兴奋，不安，夜啼，枕秃和多汗枕秃thelossofhairintheoccipitalposition活动期（激期）Advancedstage：症状symptom体征physicalsignX线表现X-raymanifestation血生化改变bloodbiochemistryClinicalmanifestation-

Advancedstage一、Osseouschanges骨骼改变1.Head头部：①颅骨软化Craniotabes

：6月以内，乒乓球颅ping-pong-ballsensation②方颅Box-likehead

：8-9月以上③前囟闭合延迟delayedclosureofanteriorfontanelle：可迟至2-3岁，头围增大④乳牙萌出延迟delayederuption,withabnormalorder,defects：可迟至10个月甚至1岁多方出牙，3岁才出齐

Skullchange头颅骨的改变

①Oneoftheearlysignsofricketsintheinfantunder6monthsofageiscraniotabes.Thethinskullbonecanbeindentedlikeaping-pongballbypressureofthefinger,snappingbackwhenthepressureisreleased.六个月以内的婴儿颅骨软化，用指尖压枕骨或顶骨的后部有压乒乓球样的感觉，松手后很快恢复。

Skullchange头颅骨的改变

②Thecentralpartsoftheparietalandfrontalbonesareoftenthickened,formingprominencesorbosses,whichgivetheheadaboxlikeappearance六个月后额骨和顶骨中心增厚，形成方盒样头

方颅Squarehead（boxlikehead）马鞍颅saddlelikehead

Skullchange头颅骨的改变

③Growthoftheskullbonesisdelayed,sothatthefontanelleandsutureclosuresaredelayed.囟门和骨缝闭合延迟Skullchange头颅骨的改变④Teethchange牙齿的改变Eruptionofthetemporaryteethmaybedelayed,andtheremaybedefectsoftheenamelandextensivecaries.Thepermanentteeththatarecalcifyingmayalsobeaffected乳牙长出晚，牙釉质缺陷和广泛龋齿，恒牙也如此extensivecaries2.Chest胸部：1岁左右①rachiticrosary肋骨串珠：又称为佝偻病串珠②pigeonchest鸡胸、funnel-shapedchest漏斗胸③Harrisongroove肋膈沟：又称郝氏沟

Enlargementofthecostochondraljunctionsmaybecomeprominent;thebeadingoftheribsisnotonlypalpablebutalsovisible.肋骨与肋软骨交界处因骨样组织堆积膨大而形成钝圆形隆起，呈串珠样改变

①

rachiticrosary肋骨串珠

rachiticrosary肋骨串珠RachiticrosaryThesternumwithitsadjacentcartilageappearstobeprojectedforward,producingtheso-calledpigeonbreastdeformity.

肋骨骺部内陷，以致胸骨向前突出，形成鸡胸。如胸骨剑突部向内凹陷，形成漏斗胸。②

pigeonchest鸡胸

Funnelbreast漏斗胸

漏斗胸

鸡胸pigeonchestfunnel-shapedchestChickenbreastAhorizontaldepression,Harrisongroove,developsalongthelowerborderofthechest.膈肌附着处的肋骨受牵拉而内陷形成的一道横沟-郝氏沟③Harrisongroove肋膈沟郝氏沟

Harrisongrooves

郝氏沟Harrisongroove3.四肢①佝偻病手、足镯：6月以上，②下肢畸形：1岁左右“O”型、“X”型、“K”型腿

Fourlimbs

Extremitieschange四肢骨改变①theepiphysealenlargementatthewristsandanklesbecomesmorenoticeable.腕和踝关节的骨骺增宽，形成钝圆形环状隆起，呈手，脚镯。braceletsofhands手镯braceletsoffeet脚镯

②Thebendingofthesoftenedshaftsofthefemur,tibia,andfibularesultsinbowlegsorknock-knees.Greenstickfracturesoccurinthelongbones;thereareoftennoclinicalsymptoms.由于骨质软化与肌肉关节松弛，小儿双下肢因负重而出现股骨、胫骨、腓骨弯曲，形成严重膝内翻（“O”型）、或膝外翻（“X”型）畸形，长骨可发生青枝骨折。下肢生理性弯曲正常下肢发育过程手镯

O型腿

X型腿4.脊柱Spinalcolumn

：kyphosis后凸畸形，严重可骨盆畸形5.肌肉改变Muscularchanges：低血磷—糖代谢障碍，表现全身肌肉松弛、乏力、肌张力降低，运动功能发育落后Motordevelopmentdelayed；腹肌张力低下，腹部膨隆成蛙腹potbelly6.Othernervousandmentalsymptoms

：神经发育迟缓—表情淡漠、语言落后；免疫力低下

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韧带松弛

脊柱后弯二、佝偻病激期血生化改变25-OHD3下降明显PTH升高明显血Ca稍降血P下降明显AKP增高明显三、佝偻病激期X线改变BlurringofthepreparatorycalcificationlineMetaphyseslikeacup骨骺端钙化带消失，呈毛刷样、杯口样改变Wideningoftheepiphysealcartilage骨骺软骨带增宽（大于2mm）rarefactionofthebone骨质稀疏，骨皮质变薄骨干弯曲畸形或青枝骨折

返回正常上肢长骨X线佝偻病上肢长骨X线正常下肢长骨X线佝偻病下肢长骨X线

佝偻病治疗前

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First

佝偻病治疗后

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Firsthealingstage恢复期：症状：减轻、消失体征：减轻、消失X线改变：治疗2~3周后有显著改善，出现不规则钙化线血生化：血Ca、P渐正常AKP1~2月降至正常

Sequelaestage

后遗症期：2岁以后多见不同程度的骨骼畸形血生化正常X线骨骼干骺端病变消失诊断症状体征血生化X线检查鉴别诊断（熟悉）一、先天性甲状腺功能低下生后2-3月开始出现甲状腺功能不足现象1、相同点：生长发育迟缓、体格明显矮小、出牙迟、前囟大而闭合晚、腹胀等。2、不同点：该病患儿智能低下、有特殊面容3、鉴别：血清TSH、T4鉴别诊断（熟悉）二、软骨营养不良1、相同点：头大、前额突出、长骨骺端膨出、胸部串珠、腹大等2、不同点：四肢及手指短粗、五指齐平，腰椎前突、臀部后突3、骨骼X线特征性改变：长骨粗短弯曲、干骺端变宽呈喇叭口状鉴别诊断（熟悉）--体征相同而病因不同三、家族性低磷血症（1）多为X连锁遗传，少数常染色体隐性遗传，也有散发（2）原发缺陷为肾小管重吸收磷和25-(OH)D3羟化障碍（3）佝偻病症状多在1岁以后，2-3岁仍有活动性佝偻病表现（4）血钙正常，血磷明显降低，尿磷增加（5）常规治疗剂量VD治疗无效，需同时口服磷鉴别诊断（熟悉）--体征相同而病因不同四、远端肾小管酸中毒（1）远曲小管泌氢不足，大量钠、钾、钙从尿中丢失，继发甲状旁腺功能亢进，骨质脱钙及佝偻病症状（2）VD疗效不显著（3）骨骼畸形明显，身材矮小（4）代酸、多尿、碱性尿，血钙、磷、钾均低，血氯高，伴低钾症状鉴别诊断（熟悉）--体征相同而病因不同五、维生素D依赖性佝偻病：常染色体隐性遗传（1）Ⅰ型：肾脏1-羟化酶缺陷，25-(OH)D3浓度高，高氨基酸尿症（2）Ⅱ型：1,25-(OH)2D3靶器官