佝偻病终稿

rickets of vitamin D deficiency （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,definition,Vitamin D deficiency 体内VD不足,a metabolic disorder of calcium and phosphorus钙磷代谢紊乱,bony deformities骨骼病变,小儿体内维生素D不足引起钙磷代谢失常的一种慢性营养性疾病。,summarize,Definition : Rickets is a very common chronic nutritional deficient disease Vitamin D deficiency cause rickets, a metabolic disorder of calcium and phosphorus with a failure to mineralize osteoid tissue of growing bone resulting in bony deformities. 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 in young children especially under two years old of age. 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,Vitamin D Metabolism and Physiology 代谢与生理,Vitamin D is a generic term for a group of steroids, the most important ingredients of which are cholecalciferol（vitamin D3）and ergocalciferol (vitamin D2 ) 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）,The natural source of vitamin D for the human is the cholecalciferol produced in the skin following exposure to the ultraviolet radiation of sunshine, which activates the skin 7- dehydrocholesterol,Vitamin D Metabolism and Physiology,VD的活化,VD在体内经两次羟化始能发挥生物效应 肝脏 肾脏VD 25-OHD 1,25-(OH)2D 25-羟化酶 1-羟化酶反映VD的营养状况(11-60ng/ml)，但生物活性微弱,肝脏羟化部位在肝细胞微粒体和线粒体中。肾脏羟化部位在肾近曲小管上皮细胞线粒体中。,维生素D促进小肠细胞吸收Ca,软骨的生长发育及与佝偻病发生,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：,骨间质，骨组织,钙离子沉积,骨发生：,软骨内成骨软骨细胞静止区 软骨细胞增生区软骨细胞肥大区基质钙化区成骨区,Index,Up,First,【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 ( ),佝偻病病理,软骨细胞肥大区的病理：由于钙磷不足而类骨质不能钙化，不钙化就不能有血管侵入，也就不能有软骨的融解与破坏，自然也就不能成骨，这就必然造成大量的软骨组织堆集，成骨区的病理改变：此区新生的骨小梁较少，且排列不规则，但因无钙沉积，所以有新形成的类骨组织堆集。, 佝偻病X线片示意图,Index,Up,First,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,Sun exposure,Mother,Source of Vit D,Food,Support two weeks,Natural foods: inadequate,Major source,Sources of Vitamin D,Sunlight is the most important source Fish liver oil Fish & sea food (herring & salmon) Eggs Plants do not contain vitamin D3,Vitamin D Sources,Not found naturally in many foodsSynthesized in bodyPlants (ergosterol)Sun-cured foragesFluid milk products are fortified with vitamin DOily fishEgg yolkButterLiverDifficult for vegetarians,Natural foodsBreast milk 1 g /LCows milk 0.5-1g /LEgg 1.75 g /100gButter 0.75-1.5g /100g,* Vit D 1 g = 40IU,Content of Vit D,表1 富含维生素D食物一览表(国际单位/100克),VD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,自身反馈,自身反馈,VD的自身反馈调节,VD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,VitD2,3,25-(OH)D3,VitD的调节；血钙磷浓度,VD代谢的调节-CT (calcitonin),血钙 CT 肾1,25(OH)2D 血磷 肾1,25(OH)2D,VitD的调节,VitD2,3,25-(OH)D3,VitD的调节,VD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。,Antirachitic function 抗佝偻病作用,1. Facilitation of intestinal absorption of calcium and phosphorus 促进小肠对钙和磷的吸收2. Direct effect on mineral metabolism of bone (deposition and reabsorption) 对骨的矿物质代谢有直接作用（沉积和重吸收）,Antirachitic function 抗佝偻病作用,3. In conjunction with parathormone and calcitonin 与甲状旁腺素和降钙素相协同4. A major role in homeostasis of calcium and phosphorus in the bodys fluids and tissues 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 Absence of sunshineVD摄入不足 Dietary deficiency 生长速度快 Rapid growth 疾病影响 Disease factors药物影响 Influence of the drug,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,Etiology,2. Improper feeding: 1) Inadequate intake of Vitamin D Breast milk 0-10IU/100ml Cows milk 0.3-4IU/100ml Egg yolk 25IU/average yolk Herring 1500IU/100g 2) Improper Ca and P ratio,Etiology,3. Fast growth, increased requirement Relative deficiency4. Diseases factors: Liver diseases, renal diseases Gastrointestinal diseases,Etiology,5. Drug factors: Antiepileptic 抗癫痫药 Glucocorticosteroid 糖皮质类固醇,发病机制 pathogenesis（掌握）：,Vitamin D - deficient rickets can be conceptualized to be the bodys attempt to maintain normal serum calcium levels. 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）,Clinical Manifestations,The disease occurs most commonly from ages of 3 months to 2 years. The principal manifestations are changes of growing skeleton, weakness and relaxation of muscles, and nonspecific neuropsychic symptoms. 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,Clinical manifestation-Early stage,Usually begin at 3 months oldSymptoms: mental psychiatric symptoms Irritability, sleepless, hidrosis多汗Signs: occipital bald 枕秃No obvious skeletal changesX ray changes: normal or change slightly,Clinical manifestation-Early stage,Laboratory findings: Serum Ca, P normal or decreased slightly AKP normal or elevated slightly 25(OH)D3 decreased Ca normal ,P normal or AKP 25-(OH)D3, PTH,Early stage,The early manifestations in rickets include irritability, restlessness, sudden crying at night, alopecia in occiput, and increased sweating particularly around the head which is irrelative with room temperature and seasons. 初期，表现为兴奋，不安，夜啼，枕秃和多汗,枕秃,the loss of hair in the occipital position,活动期（激期） Advanced stage ： 症状 symptom 体征 physical sign X线表现 X-ray manifestation 血生化改变 blood biochemistry,Clinical manifestation- Advanced stage,一、Osseous changes 骨骼改变 1. Head 头部：颅骨软化 Craniotabes ：6月以内， 乒乓球颅 ping-pong-ball sensation 方颅 Box-like head ：8-9月以上前囟闭合延迟 delayed closure of anterior fontanelle ：可迟至2-3岁，头围增大乳牙萌出延迟delayed eruption, with abnormal order, defects ：可迟至10个月甚至1岁多方出牙，3岁才出齐,Skull change 头颅骨的改变 One of the early signs of rickets in the infant under 6 months of age is craniotabes. The thin skull bone can be indented like a ping - pong ball by pressure of the finger, snapping back when the pressure is released. 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。,Skull change 头颅骨的改变 The central parts of the parietal and frontal bones are often thickened, forming prominences or bosses, which give the head a boxlike appearance 六个月后额骨和顶骨中心增厚，形成方盒样头,方颅,Square head（ boxlike head）,马鞍颅saddle like head,Skull change 头颅骨的改变 Growth of the skull bones is delayed, so that the fontanelle and suture closures are delayed. 囟门和骨缝闭合延迟,Skull change 头颅骨的改变,Teeth change 牙齿的改变 Eruption of the temporary teeth may be delayed, and there may be defects of the enamel and extensive caries. The permanent teeth that are calcifying may also be affected 乳牙长出晚，牙釉质缺陷和广泛龋齿，恒牙也如此,extensive caries,2. Chest 胸部：1岁左右 rachitic rosary 肋骨串珠：又称为佝偻病串珠 pigeon chest 鸡胸 、funnel-shaped chest 漏斗胸 Harrison groove 肋膈沟：又称郝氏沟,Enlargement of the costochondral junctions may become prominent; the beading of the ribs is not only palpable but also visible. 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, rachitic rosary 肋骨串珠,rachitic rosary,肋骨串珠 Rachitic rosary,The sternum with its adjacent cartilage appears to be projected forward, producing the so-called pigeon breast deformity. 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。, pigeon chest 鸡胸 Funnel breast 漏斗胸,漏斗胸 鸡 胸,pigeon chest,funnel-shaped chest,Chicken breast,A horizontal depression, Harrison groove, develops along the lower border of the chest. 膈肌附着处的肋骨受牵拉而内陷形成的一道横沟-郝氏沟, Harrison groove 肋膈沟,郝氏沟 Harrison grooves,郝氏沟Harrison groove,3. 四肢佝偻病手、足镯：6月以上，下肢畸形：1岁左右 “O”型、 “X”型、“K”型腿,Four limbs,Extremities change 四肢骨改变 the epiphyseal enlargement at the wrists and ankles becomes more noticeable. 腕和踝关节的骨骺增宽，形成钝圆形环状隆起，呈手，脚镯。,bracelets of hands 手 镯,bracelets of feet 脚 镯, The bending of the softened shafts of the femur, tibia, and fibula results in bowlegs or knock - knees. Greenstick fractures occur in the long bones; there are often no clinical symptoms. 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Spinal column ： kyphosis 后凸畸形，严重可骨盆畸形5.肌肉改变 Muscular changes： 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Motor development delayed ；腹肌张力低下，腹部膨隆成蛙腹potbelly6. Other nervous and mental symptoms ：神经发育迟缓表情淡漠、语言落后；免疫力低下 返回,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,Blurring of the preparatory calcification lineMetaphyses like a cup骨骺端钙化带消失，呈毛刷样、杯口样改变Widening of the epiphyseal cartilage骨骺软骨带增宽（大于2mm）rarefaction of the bone 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,Index,Up,First, 佝偻病治疗后,Index,Up,First,healing stage 恢复期 ： 症状：减轻、消失 体征：减轻、消失 X线改变：治疗23周后有显著改善，出 现不规则钙化线 血生化：血Ca、P渐正常 AKP 12月降至正常,Sequelae stage 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）型：肾脏1-