<4D F736F F F696E74202D20B8DFB8C6D1AAD6A2B2A1C0FDCCD6C2DB>

Size: px

Start display at page:

Download "<4D F736F F F696E74202D20B8DFB8C6D1AAD6A2B2A1C0FDCCD6C2DB>"

扬缪
5 years ago
Views:

1 高钙血症病例讨论中山大学附属第一医院儿科黄柳一

2 病例特点 5M, 男体重不增抬头不稳反复泌尿系感染右肾及输尿管积液血 Ca Ca/Cr IPTH 25(OH)D P N ALP

3 是否高钙血症

4 高钙血症的定义成人血钙 2.65mmol/L(2 次 ) 或游离钙 1.35mmol/L 儿童血钙 2.70mmol/L(2 次 ) 或游离钙 1.40mmol/L J Intensive Care Med, 2014

5 Representative normal values for age for concentrations of serum total calcium Age(yr) Serum total calcium(mg/dl) Mmol/L Infants Children Adult > Curr Opin Pediatr, 2010

6 是否真性高钙血症

7 Distribution of calcium. Calcuium Extracellular fluid mmol/l Intracellular fluid cytosol 0.1 μmol/l, ionized calcium nmol/l Protein bound 40% Ionized 50% Complexed 10% Albumin 80% Globulin 20% Crit Rev Clin Lab Sci, 2014

8 白蛋白与球蛋白对血钙的影响低白蛋白时可引起血钙 ( 假阴性 ) 一般不引起症状性低钙高球蛋白时可引起血钙 ( 假阳性 ) 一般不引起症状性高钙不影响离子钙 Crit Rev Clin Lab Sci, 2014

9 如何鉴别假性高钙血症假性高钙血症血浆蛋白不正常致血钙而离子钙正常鉴别方法校正钙 = 实测 Ca+(40- 实测 A)x0.02 (Ca 单位 mmol/l, 白蛋白 g/l) 检测离子钙 (>1.35mmol/L) Crit Rev Clin Lab Sci, 2014 A 或 10g/L, 血 Ca 或 0.2mmol/L

10 高钙血症严重吗

11 高钙血症的严重程度分类轻度血钙 mmol/L. 血钙升高程度中度血钙 mmol/L 3 血钙升高速度重度血钙 >3.4mmol/L 机体耐受程度轻中度可无症状或非特异, 严重可致死 J Intensive Care Med, 2014

12 Manifestations of Hypercalcemia. Feeding difficulties, undergrowth J Intensive Care Med, 2014

13 如何判断高钙危象血钙 >3.75mmol/L(3.5mmol/L) 全身软弱昏迷木僵精神失常心律失常, 甚至心跳骤停氮质血症死亡紧急处理 J Intensive Care Med, 2014

14 高钙血症的原因

15 血钙的调节体内 Ca 稳定由 3 种激素 3 个器官参与调节 PTH 1,25(OH)2-D 降钙素骨骼肠道肾脏

16 Regulation of calcium homeostasis Hormones Effect on Effect on intestine Effect on Blood bones kidneys level PTH Bone 1,25(OH) 2 D Ca 2+ resorption Indirectly Ca 2+, PO 4 reabsorption absorption PO 4 reabsorption Ca 2+ PO 4 125(OH) 1, D Weak effect Ca, PO 4 absorption Weak effect on Ca 2+ on bone resorption Ca 2+ reabsorption PO 4 Calcitonin Bone resorption No direct effects Ca 2+, PO 4 reabsorption Ca 2+ PO 4 任一环节异常高钙血症 Crit Rev Clin Lab Sci, 2014

17 高钙血症的原因 PTH 相关疾病恶性肿瘤 VitD 中毒或相关疾病肾性骨营养不良其他内分泌疾病药物性制动钙敏感受体基因突变其他成人原发性甲旁亢及恶性肿瘤占 90% 儿童常见原因与年龄相关

18 PTH 相关疾病原发性甲状旁腺功能亢进甲状旁腺腺瘤增生癌多发性内分泌瘤 I 型 II 型甲旁亢 - 颌面肿瘤综合症暂时性继发性新生儿甲旁亢三发性甲状旁腺功能亢进 PTH P J Intensive Care Med, 2014

19 恶性肿瘤乳腺癌肺癌肾癌头颈肿瘤白血病淋巴瘤骨髓瘤神经母细胞瘤骨转移 PTHrP PTH P 1,25(OH)D 异位 PTH ( 少见 ) Horm Metab Res, 2010

20 VitD 中毒或相关疾病 VitD 中毒 ( 外源性 VitD ) 肉芽肿病淋巴瘤皮下脂肪坏死 ( 内源性 VitD) 外 25(OH)D 1,25(OH)D N/ PTH P 内 25(OH)D N 1,25(OH)D PTH P Curr Opin Pediatr, 2010

21 Granulomatous Diseases Causing Hypercalcemia Sarcoidosis Tuberculosis Leprosy Coccidiomycosis Histoplasmosis Candidiasis Eosinophilic granuloma Plasma cell granuloma Wegener s granulomatosis Berylliosis Silicone-induced granuloma Lymphoma Am J Med Sci, 2007

22 肾性骨营养不良慢性肾衰横纹肌溶解的恢复期及急性肾衰肾移植 P PTH 1,25(OH)D J Intensive Care Med, 2014

23 其他内分泌疾病甲状腺毒症 PTH P AKP 肾上腺皮质功能减低嗜咯细胞瘤甲状腺功能低下 J Clin Endocrinol Metab, 2005

24 药物性高血钙 VitA 中毒 VitD 中毒钙剂噻嗪类利尿剂锂锰茶碱胃肠外营养病史提示

25 制动致高血钙腿部骨折烧伤脊髓瘫痪长期卧床尿 Ca PTH 1,25(OH)D P J Intensive Care Med, 2014

26 钙敏感受体基因突变 ( 甲状旁腺肾 ) 家族性良性低尿钙高血钙尿 Ca 尿 Ca /Cr < 0.01 PTH N 或稍 25(OH)D N P 新生儿严重甲旁亢 PTH 血 Ca FHH 常显杂合子部分受体缺陷血钙较轻 NSHPT 常隐纯合子完全受体缺陷血钙严重 J Clin Endocrinol Metab, 2013

27 其他少见疾病特发性婴儿高钙血症 /William 综合症 1,25(OH)D PTH Jansen 干端软骨发育不良低磷血症 PTH P 1,25(OH )D AKP P 1,25(OH )D 低磷酸酯酶症 ALP P N 尿钙 J Clin Endocrinol Metab, 2005

28 其他少见疾病 Lactase deficiency Disaccharide intolerance Down syndrome Blue diaper syndrome Bartter syndrome Curr Opin Pediatr, 2010

29 特发性婴儿高钙血症常染色体隐性遗传 CYP24A 突变 1,25(OH)D 25(OH)D CYP24A 突变表型轻重不一肌张力减退口渴厌食消瘦精神运动迟缓便秘肾钙质沉着 1,25(OH)D PTH P Endocr prct, 2014

30 (A) normal vitamin D metabolism; (B) effects of 24-hydroxylase (A) normal vitamin D metabolism; (B) effects of 24 hydroxylase defiiency. 25-OH-D = 25-hydroxyvitamin D; 1,25-(OH)2D = 1,25- dihydroxyvitamin D. Endocr prct, 2014

31 如何诊断高钙血症

32 高钙血症的诊断病史钙 VitD 摄入史其他药物摄入史潜在疾病年龄

Differential diagnosis of hypercalcemia in neonates and infants (up to 2 years of age) Phosphate Depletion Hypophosphatentasia

hyperplasia Maternal hypoparathyroidism Inactivating mutations in Ca 2+ -sensing receptor gene - Familial hypocalciuric

necrosis Williams syndrome/idiopathic infantile hypercalcemia Other inborn metabolic disorders - Blue diaper syndrome Lactase

33 Differential diagnosis of hypercalcemia in neonates and infants (up to 2 years of age) Phosphate Depletion Hypophosphatentasia Premature infants on human milk or standard formula Parenteral nutrition Hyperparathyroidism p y - Congenital parathyroid hyperplasia Maternal hypoparathyroidism Inactivating mutations in Ca 2+ -sensing receptor gene - Familial hypocalciuric hypercalcemia Neonatal severe hyperparathyroidism Jansen s metaphyseal chondrodysplasia Hypervitaminosis D Subcutaneous fat necrosis Williams syndrome/idiopathic infantile hypercalcemia Other inborn metabolic disorders - Blue diaper syndrome Lactase deficiency - Disaccharide intolerance Bartter syndrome Down syndrome Severe congenital hypothyroidism Maternal hypercalcemia Vitamin A intoxication Curr Opin Pediatr, 2010

34 高钙血症的诊断实验室检查血 Ca 24h 尿 Ca 尿 Ca/Cr PTH PTHrP 1,25(OH)D P AKP Mg BUN Cr A G 甲状腺功能皮质醇基因检测其他 X 线骨扫描骨髓象等

35 Investigation of hypercalcemia. Crit Rev Clin Lab Sci, 2014

36 如何处理高钙血症

37 高钙血症的治疗措施 (1) 补液 (NS 或 2/3 张 ) 尿钙排泄通过稀释血 Ca 利尿 Lasix or HCT? 糖皮质激素阻断 1,25(OH)D 的作用尿 Ca 排泄降钙素抑制骨的重吸收肾小管 Ca 重吸收尿 Ca 排泄 J Intensive Care Med, 2014

38 高钙血症的治疗措施 (2) 二磷酸盐作用于破骨细胞而抑制骨重吸收血透用低或无钙的透析液低 Ca 低 VitD 饮食 (Calciloxo- 低 Ca 无 VitD 配方 ) 手术原发性甲旁亢 ( 儿童 ) 严重新生儿甲旁亢原发病的治疗 J Intensive Care Med, 2014

39 各种治疗方法的特点糖皮质激素起效慢维持时间短特别适用于 1,25(OH)D 机制者肿瘤等降钙素起效迅速 (2-4h 内 ) 不良反应小降 Ca 效果小 ( < 3mg/dl), 维持时间短, 易产生耐受二磷酸盐降 Ca 效果显著持续时间长 (1-3 周 ) 起效慢 (2-4 天 ), 儿童少用 ( 肾损骨发育 ) 适用于高血 Ca 伴低 P 透析迅速起效, 适用于伴有急性或慢性肾衰

40 高钙血症的治疗选择高钙危象盐水降钙素透析慢性高钙血症饮食疗法二膦酸盐糖皮质激素不同病情, 选择不同治疗方式 J Intensive Care Med, 2014

42 Laboratory values in differential diagnosis of hypercalcemia. Serum calcium Serum phosphorus Fractional excretion of calcium PTH PTHrP 25(OH)D 1,25(OH)D Familial hypocalciuric Nor < Nor N hypercalcemia NSHPT < 0.01 N or Subcutaneous fat N necrosis Williams syndrome N N or Primary >0.01 N hyperparathyroidism Humoral Malignancy a N N or Osteolytic malignancy N Granulomatous disease N Vitamin D intoxication N or Immobilization N Crit Rev Clin Lab Sci, 2014

43 Total body calcium.

phosphate parathyroid Adapted from: Kelly

In: Kappy MS, Allen DB, Geffner ME editor.

44 Hypercalcemia algorithm Adapted from: Kelly A Levine MA Disorders of calcium phosphate parathyroid Adapted from: Kelly A, Levine MA. Disorders of calcium, phosphate,parathyroid hormoneand vitamin D. In: Kappy MS, Allen DB, Geffner ME editor. Pediatric Practice: Endocrinology.Springfield: Charles C. Thomas Publisher, LTD; p

45 Hypercalcemia in children (over 2 years of age) and adolescents Excessive calcium intake Phosphate depletion Parenteral nutrition Hyperparathyroidism Hypervitaminosis D Excessive intake Granulomatous diseases: cat scratch fever; sarcoidosis; tuberculosis; histoplasmosis; coccidiomycosis; leprosy; HIV Chronic inflammatory disorders Acquired primary Malignancy associated hypercalcemia adenoma multi-glandular Primary bone tumors Metastatic tumors with osteolysis carcinoma Genetic primary Hepatic disease Tumors secreting PTHrP, prostaglandins, cytokines, growth factors autosomal dominant/récessive FHH familial MEN types I and IIa (IIb) Hyperthyroidism Adrenal insufficiency Pheochromocytoma Hyperparathyroidism-Jaw tumor Vasoactive intestinal polypeptide-secreting tumor Autonomous (tertiary) Drugs (thiazides, lithium, systemic retinoid derivatives, theophylline, acetosalicylic acid) Williams syndrome/ Idiopathic infantile hypercalcemia Milk alkali syndrome/ calcium gluttony

<4D6963726F736F667420576F7264202D2031302EBDCDB674A662A448C5E9A4BAAABAA76CA6ACBB50A54EC1C22E646F63>

<4D6963726F736F667420576F7264202D2031302EBDCDB674A662A448C5E9A4BAAABAA76CA6ACBB50A54EC1C22E646F63> 談鈣在人體內的吸收與代謝林文彬林園中醫診所 TEL:02-29609611 FAX:02-29694268 E-mail:lin5400@ms19.hinet.net 通訊處 : 板橋市林園街 24 號摘要成年人骨含鈣量約爲 1180g, 鈣在人體組織的代謝過程中主要受副甲狀腺素腎上