低钾血症诊断策略.ppt

低钾血症诊断策略,成都军区总医院内分泌科 游志清,主要内容,钾平衡低血钾常见原因低钾血症的诊断流程,主要内容,钾平衡低血钾常见原因低钾血症的诊断流程,人体钾的数据,正常血钾浓度3.55.5mmol/L体内钾总量。男性5055mmol/Kg，女性4050mmol/Kg钾的分布:细胞内98%，细胞外2%钾的生理需要量:0.4mmol/Kg,34g（75100mmol）钾的排泄:肾85%，粪10%，汗5%无钾摄入，肾排钾4050mmol/日,钾平衡,在细胞内液（ICF）中K+中的浓度比细胞外液（ECF）中的高 30-50倍，每日摄入K+量大约与ECF K+相当。维护正常的血清K+浓度需要在ECF 和ICF之间精细调节K+的分布（内部K+平衡）和肾排泄K+（外部K+平衡）。无论是在内部（ECF 和ICF）之间平衡紊乱（例如 K+的转移）或外部平衡（如K+的消耗），均可导致低钾血症。,转运K+的主要途径维持细胞内高钾,Electrolyte Blood Press 8:38-50,2010,（Na+/H+exchanger）,Metabolic alkalosis,Cortical collecting duct,ROMK,（Renal outer medullary K+Channel）,阿米洛利：作用于肾脏远端小管，阻断Na+-K+交换机制，促使钠、氯排泄而减少钾和氢离子分泌,氢氯噻嗪主要抑制远端小管前段和近端小管(作用较轻)对氯化钠的重吸收，从而增加远端小管和集合管的Na+-K+交换，K+分泌增多。,氨苯喋啶：直接抑制肾脏远端小管和集合管的Na+-K+交换，从而使Na+、C1-、水排泄增多，而K+排泄减少,呋噻米本类药物主要通过抑制肾小管髓袢厚壁段对氯化钠的主动重吸收（抑制基底膜外侧存在与Na+-K+-ATP酶有关的Na+、Cl-配对转运系统），远端小管Na+浓度升高，促进Na+-K+和Na+-H+交换增加，K+和H+排出增多。通过抑制亨氏袢对Ca2+、Mg2+的重吸收而增加Ca2+、Mg2+排泄。尚可能抑制近端小管和远端小管对Na+、Cl-的重吸收，促进远端小管分泌K+。,呋噻米：本类药物主要通过抑制肾小管髓袢厚壁段对氯化钠的主动重吸收，结果管腔液Na+、C1-浓度升高，而髓质间液Na+、Cl-浓度降低，使渗透压梯度差降低，肾小管浓缩功能下降，从而导致水、Na+、Cl-排泄增多。由于Na+重吸收减少，远端小管Na+浓度升高，促进Na+-K+和Na+-H+交换增加，K+和H+排出增多。至于呋塞米抑制肾小管髓袢升支厚壁段重吸收Cl-的机制，过去曾认为该部位存在氯泵，目前研究表明该部位基底膜外侧存在与Na+-K+-ATP酶有关的Na+、Cl-配对转运系统，呋塞米通过抑制该系统功能而减少Na+、C1-的重吸收。另外，呋塞米可能尚能抑制近端小管和远端小管对Na+、Cl-的重吸收，促进远端小管分泌K+。呋塞米通过抑制亨氏袢对Ca2+、Mg2+的重吸收而增加Ca2+、Mg2+排泄,肾对的K+调控,经肾小球滤过的K+大部分被近曲小管和亨利氏袢重吸收终尿中的K+最终主要是由远曲小管（DCT）远端，连接小管和皮层集合管（CCD）控制。有两个因素影响K+的排泄：CCD终端流速=尿渗透压容积/血浆渗透压 或尿渗透压/肌酐 CCD主细胞净分泌K+(K+CCD)=（尿/血浆K+)/(尿/血浆渗透压）,肾对的K+调控,Q J Med 2005;98:305316,ENaC,epithelial Na+channels,肾对的K+调控,Q J Med 2005;98:305316,肾对的K+调控,Electrolyte Blood Press 8:38-50,2010,CCD,cortical collecting ductENaC,epithelial Na+channels.,Aldosterone,+,HCO3,plasma K+3.5mmol/L,TTKG 3indicates fast Na+or slow Cl disorders,K+：ROMK,+,-,ENaC,epithelial Na+channels,主要内容,钾平衡低血钾常见原因低钾血症的诊断流程,低血钾原因,缺钾性 摄入不足，3克/日，2周 排出过多 肾，胃肠，其他转移性：代碱，大量糖（+胰岛素），周瘫，应急，棉子油，氯化钡，叶酸，维生素B12稀释性：水过多，水中毒,主要内容,钾平衡低血钾常见原因低钾血症的诊断流程病史肾排钾评估血压血气分析血、尿电解质，RASS，皮质醇及ACTH,病史,起病急缓伴随症状过去史药物史家族史,评判肾排钾的指标，尤其是低钾麻痹时,常用的4个指标，均为随意尿fractional excretion of K+,K+排泄分数TTKG,transtubular K+gradient，跨小管 K+梯度urine K+/creatinine ratio，尿 K+/肌酐比值urine osmolality/creatinine，尿渗透压/肌酐比值主要目的：是否为肾排钾增多,Arch Intern Med.2004;164:1561-1566,A spot urine sample,Hypokalemic periodic paralysis(n=30),Nonhypokalemic periodic paralysis(n=13),a plasma K+3 mmol/L,TTKG,transtubular K+gradient,=(urine/plasma K+)/(urine/plasma osmolality).,RVH,renal vascular hypertension CAH,congenital adrenal Hyperplasia RTA,renal tubular acidosisCOA,coarctation of the aorta DKA,diabetic ketoacidosisRST,renin-secreting tumorsAME,apparent mineralocorticoid excess.,P,potassiumC,creatinine,GI,gastrointestinal,PP,periodic paralysis,PRA,plasma renin activityPAC,plasma aldosterone concentration,IJKD 2008;2:115-22,Andersen-Tawil syndrome,：CLD,CLD：Congenital chloride-losing diarrhea,Patients with a potassium excretion rate of 10 mmol/d to 15 mmol/d and a creatinine excretion rate of 10 mmol/d to 15 mmol/d will have a urine K/C ratio less than 1.5.-J Clin Invest 1959;38:114965,Cystic fibrosis,Andersen-Tawil syndrome,It is an autosmal-dominant channelopathy resulting in episodic attacks of muscle weakness(mainly acute hypokalemia,but can be normo-or hyperkalemia),cardiac arrhythmia(ventricular arrhythmias and QT prolongation)and distinctive physical features.These features often include a very small lower jaw(小颌畸形),dental abnormalities,low-set ears,widely spaced eyes,and unusual curving of the fingers or toes(clinodactyly).Some affected people also have short stature and an abnormal curvature of the spine(脊柱侧弯).,Andersen-Tawil syndrome,Two types of Andersen-Tawil syndrome are distinguished by their genetic causes.Type 1,which accounts for about 60 percent of all cases of the disorder,is caused by mutations in the KCNJ2 gene.The remaining 40 percent of cases are designated as type 2;the cause of these cases is unknownMutations in the gene KCNJ2 encoding a pore-forming subunit of the inward rectifier K channel protein,Kir2.1,which is expressed in skeletal muscles and heart,lead to this syndrome,Congenital chloride-losing diarrhea(CLD),Congenital chloride-losing diarrhea(CLD)is a rare autosomal recessive disorder characterized by watery diarrhea,hypokalemia and hypochloremic metabolic alkalosis with high fecal content of Cl(90 mEq/L),Cystic fibrosis,Cystic fibrosis(CF)is an exocrine disease affecting multiple organ systems.The defect in the cystic fibrosis transmembrane regulator(CFTR),acting primarily as a Cl channel,is associated with CF,.Hypokalemia is not uncommon in patients with CF,especially in tropical or subtropical areas.Defective chloride reabsorption by the dysfunctional CFTR in the sweat ducts of CF patients is responsible for excessive Cl and Na+loss in sweat.ECF volume depletion with secondary hyperaldosteronism not only causes Na+reabsorption and K+secretion in the CCD,but may also augment K+secretion in sweat ducts and thereby contribute to the hypokalemia.,Electrolyte Blood Press 8:38-50,2010,ECF,extracellular fluid BP,blood pressure,ECF,BP,RVH:right ventricular hypertrophy,AME:Apparent mineralocorticoid excess,DOC:11-deoxycorticosterone,Electrolyte Blood Press 8:38-50,2010,ECF,extracellular fluid BP,blood pressure,Liddles syndrome,其原因是.ENaC的或单位突变，导致其胞浆内C末端丢失或结构变化。突变后的 ENaC 保持被激活形式。not internalized(clathrin-coated pits pathway)or degraded(Nedd4 pathway)突变后的 ENaC对阿米洛利和氨苯喋啶敏感,Apparent mineralocorticoid excess(AME),AME,caused by mutations in the gene(HSD11B2)encoding renal-specific 11-hydroxysteroid dehydrogenase type 2(11-HSD2).is a rare but potentially fatal autosomal recessive form of hypertension and hypokalemic metabolic alkalosis associated with hyporeninemia and hypoaldosteronemia and an abnormal ratio of urinary metabolites of cortisol with a high tetrahydrocortisol:tetrahydrocortisone(THF:THE)ratio,11-HSD2,Cortisol,cortisone,MR,+,The principal cells of distal tubules,lycyrrhetinic acid,Electrolyte Blood Press 8:38-50,2010,ECF,BP,RTA,renal tubular acidosisGS,Gitelmans syndromeBS,Bartters syndrome,Bartters syndrome(BS)and Gitelmans syndrome(GS),BS results from defective reabsorption of NaCl in the LOH whereas GS is secondary to defective reabsorption of NaCl in the DCT.High urine Ca2+and Mg2+excretion is universally present in lesions of the loop of Henle(LOH)whereas low urine Ca2+and high Mg2+excretion is invariably found in lesions of the distal convoluted tubule(DCT),CTAL,cortical thick ascending limb,Bartters syndrome(BS)and Gitelmans syndrome(GS),The five subtypes of BS arise from inactivation mutations in genes encoding the Na+/K+/2Cl cotransporter(NKCC2),K+channel(ROMK),kidney-specific Cl channel(CLCNKB),barttin(BSND)and calcium-sensing receptors(CaSR),Fig.Transport proteins in the thick ascending limb(TAL)of loop of Henle(LOH)(left panel)and distal convoluted tubule(DCT)(right panel)affected by gene mutations.,Electrolyte Blood Press 8:38-50,2010,Bartters syndrome(BS)and Gitelmans syndrome(GS),At the molecular level,GS is mostly due to inactivating mutations in the SLC12A3 gene,which encodes the thiazide-sensitive Na+/Cl cotransporter(NCC)on the apical membrane of the DCT,Fig.Mechanisms for persistent hypokalemia in Gitelmans syndrome(GS),ROMK,renal outer medullary K+channel CNT,cortical connecting tubulesNCC,thiazide-sensitive Na+/Cl cotransporter,Electrolyte Blood Press 8:38-50,2010,Bartters syndrome(BS)and Gitelmans syndrome(GS),A maternal history of polyhydramnios,age of onset,neurologic symptoms,deafness,presence of nephrocalcinosis or renal stones,and serum divalent concentration with their urine excretion rates help distinguish among the subtypes of BS and GS.Because Cl-channels are expressed in both the basolateral membrane of LOH and DCT,some patients with classical BS may have clinical profiles similar to that of GS.,Bartters syndrome(BS)and Gitelmans syndrome(GS),Unlike BS,non-steroid anti-inflammatory drugs(NSAIDs)are usually not effective in patients with GS due to the relatively normal urinary prostaglandin E2 excretion.,Characteristic of Bartters syndrome(BS)and Gitelmans syndrome(GS),AR,autosomal recessive,SeSAME,seizures,sensorineural deafness,ataxia,mental retardation,and electrolyte imbalance,PHYSIOLOGICAL REVIEWS Vol.80,No.1,January 2000,Orphanet Journal of Rare Diseases 2008,3:22,DCT-1(top)and DCT-2(bottom)cells in normal(left)and Gitelmans(right)individuals are shown.,PHYSIOLOGICAL REVIEWS Vol.80,No.1,January 2000,17-羟化酶缺乏，最多见于女性患者，有些到成年表现为皮质醇低水平，ACTH代偿性增高。原发性闭经，性幼稚，很少有男性假两性畸形。盐类皮质激素分泌过多引起高血压，以11-脱氧皮质酮增高为主。部分联合缺乏17,20裂解酶，不缺乏皮质醇，无肾上腺皮质增生。,11-羟化酶缺乏使皮质醇和皮质酮的形成受阻，ACTH释放过高，致深度黑色素沉着，由于11-去氧皮质酮分泌过量而引起高血压，无明显性征异常。,21-羟化酶的不足或缺乏使17-羧孕酮不能转化为皮质醇，多见的不足有二种形式：（1）多种多样的丢钠，醛固酮低或缺乏；（1）更常见的是非丢钠型，多毛，男性化，低血压和色素沉着常见。,Hyperchloremic metabolic acidosis-renal tubular acidosis(RTA),Hyperchloremic metabolic acidosis involving both K+depletion and direct or indirect loss of HCO3An indirect estimate of NH4+can be obtained from the urine anion gap(Na+K+Cl)or osmolal gap(measured-calculated urine osmolality)/2.Positive urine net charge and osmolal gap less than 100 mOsm/kg H2O are indicative of low urine NH4+excretion,pointing to the diagnosis of RTA.Intravenous NaHCO3 loading at a rate of 2-3 mEq/kg/hour can be administered to separate proximal from distal RTA,谢谢!,