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1、低钾血症诊断策略低钾血症诊断策略主要内容主要内容l钾平衡钾平衡l低血钾常见原因低血钾常见原因l低钾血症的诊断流程低钾血症的诊断流程主要内容主要内容l钾平衡钾平衡l低血钾常见原因低血钾常见原因l低钾血症的诊断流程低钾血症的诊断流程人体钾的数据人体钾的数据l正常血钾浓度正常血钾浓度3.55.5mmol/Ll体内钾总量。男性体内钾总量。男性5055mmol/Kg，女性，女性4050mmol/Kgl钾的分布钾的分布:细胞内细胞内98%，细胞外，细胞外2%l钾的生理需要量钾的生理需要量:0.4mmol/Kg,34g（75100mmol）l钾的排泄钾的排泄:肾肾85%，粪，粪10%，汗，汗5%l无钾摄入，
2、肾排钾无钾摄入，肾排钾4050mmol/日日钾平衡钾平衡l在细胞内液（在细胞内液（ICF）中）中K +中的浓度比细胞外液中的浓度比细胞外液（ECF）中的高）中的高 30-50倍，每日摄入倍，每日摄入K +量大约与量大约与ECF K +相当。相当。l维护正常的血清维护正常的血清K+浓度需要在浓度需要在ECF 和和ICF之间精细调之间精细调节节K+的分布（内部的分布（内部K+平衡）和肾排泄平衡）和肾排泄K+ （外部（外部K+平平衡）。衡）。l无论是在内部（无论是在内部（ECF 和和ICF）之间平衡紊乱（例如）之间平衡紊乱（例如 K+的转移）或外部平衡（如的转移）或外部平衡（如K+的消耗），均可导致
3、的消耗），均可导致低钾血症。低钾血症。转运转运K+的主要途径的主要途径维持细胞内高钾维持细胞内高钾Electrolyte Blood Press 8:38-50, 2010（Na+/H+ exchanger）Metabolic alkalosisCortical collecting ductCortical collecting ductROMK（Renal outer medullary K+ Channel）阿米洛利：作用于阿米洛利：作用于肾脏远端小管，阻肾脏远端小管，阻断断Na+-K+交换机制，交换机制，促使钠、氯排泄而促使钠、氯排泄而减少钾和氢离子分泌减少钾和氢离子分泌氢氯噻嗪主要抑
4、制氢氯噻嗪主要抑制远端小管前段和近远端小管前段和近端小管端小管(作用较轻作用较轻)对氯化钠的重吸收对氯化钠的重吸收，从而增加远端小，从而增加远端小管和集合管的管和集合管的Na+-K+交换，交换，K+分泌分泌增多。增多。氨苯喋啶：直接抑制氨苯喋啶：直接抑制肾脏远端小管和集合肾脏远端小管和集合管的管的Na+-K+交换，交换，从而使从而使Na+、C1-、水排泄增多，而水排泄增多，而K+排泄减少排泄减少 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（抑制基底膜外侧存在与Na+-K+-ATP酶有关的酶有
5、关的Na+、Cl-配对转运系统）配对转运系统），远端小管，远端小管Na+浓度升高，促进浓度升高，促进Na+-K+和和Na+-H+交换增加，交换增加，K+和和H+排排出增多。通过抑制亨氏袢对出增多。通过抑制亨氏袢对Ca2+、Mg2+的重吸收而增加的重吸收而增加Ca2+、Mg2+排泄。尚可能抑制近端小管和远端小管对排泄。尚可能抑制近端小管和远端小管对Na+、Cl-的重吸收，的重吸收，促进远端小管分泌促进远端小管分泌K+。l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，结果管腔液动重吸收，结果管腔液Na+、C1-浓度升高，而
6、髓质间液浓度升高，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、而导致水、Na+、Cl-排泄增多。由于排泄增多。由于Na+重吸收减少，远端小管重吸收减少，远端小管Na+浓度升高，促进浓度升高，促进Na+-K+和和Na+-H+交换增加，交换增加，K+和和H+排出排出增多。至于呋塞米抑制肾小管髓袢升支厚壁段重吸收增多。至于呋塞米抑制肾小管髓袢升支厚壁段重吸收Cl-的机制，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在与Na+-K
7、+-ATP酶有关的酶有关的Na+、Cl-配对转运系统，呋塞米通过配对转运系统，呋塞米通过抑制该系统功能而减少抑制该系统功能而减少Na+、C1-的重吸收。另外，呋塞米可能的重吸收。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，促进远端小的重吸收，促进远端小管分泌管分泌K+。呋塞米通过抑制亨氏袢对。呋塞米通过抑制亨氏袢对Ca2+、Mg2+的重吸收而的重吸收而增加增加Ca2+、Mg2+排泄排泄 肾对的肾对的K+调控调控l经肾小球滤过的经肾小球滤过的K K+ +大部分被近曲小管和亨利氏袢重吸大部分被近曲小管和亨利氏袢重吸收收l终尿中的终尿中的K K+
8、+最终主要是由远曲小管（最终主要是由远曲小管（DCTDCT）远端，连接）远端，连接小管和皮层集合管（小管和皮层集合管（CCDCCD）控制。）控制。l有两个因素影响有两个因素影响K K+ +的排泄：的排泄：CCDCCD终端流速终端流速= =尿渗透压尿渗透压容积容积/ /血浆渗透压血浆渗透压 或尿渗透压或尿渗透压/ /肌酐肌酐 CCD CCD主细胞净分泌主细胞净分泌K K+ +( K( K+ + CCDCCD)=)=（尿（尿/ /血浆血浆KK+ +)/()/(尿尿/ /血血浆渗透压）浆渗透压）肾对的肾对的K+调控调控Electrolyte Blood Press 8:38-50, 2010CCD,
9、cortical collecting ductENaC,epithelial Na+ channels.Aldosterone+HCO3plasma K+90 mEq/L)Cystic fibrosislCystic 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
10、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
11、 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. Liddles syndromel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。l突变后的 ENaC 保持被激活形式。 not internalized (clathrin-coated pits pathway) or degraded (Nedd4 pathway
12、)l突变后的 ENaC对阿米洛利和氨苯喋啶敏感Apparent mineralocorticoid excess (AME)lAME ,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 associa
13、ted with hyporeninemia and hypoaldosteronemia and an abnormal ratio of urinary metabolites of cortisol with a high tetrahydrocortisol:tetrahydrocortisone (THF:THE) ratio11-HSD2CortisolcortisoneMR+The principal cells of distal tubuleslycyrrhetinic acidElectrolyte Blood Press 8:38-50, 2010ECF, BPRTA,r
14、enal tubular acidosisGS,Gitelmans syndromeBS,Bartters syndromeBartters syndrome (BS) and Gitelmans syndrome (GS)lBS results from defective reabsorption of NaCl in the LOH whereas GS is secondary to defective reabsorption of NaCl in the DCT.lHigh urine Ca2+ and Mg2+ excretion is universally present i
15、n 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)lThe five subtypes of BS arise from inactivation mutations in g
16、enes 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
17、) affected by gene mutations.Electrolyte Blood Press 8:38-50, 2010Bartters syndrome (BS) and Gitelmans syndrome (GS)lAt 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 D
18、CTFig. Mechanisms for persistent hypokalemia in Gitelmans syndrome (GS)ROMK, renal outer medullary K+ channel CNT, cortical connecting tubulesNCC, thiazide-sensitive Na+/Cl cotransporterElectrolyte Blood Press 8:38-50, 2010Bartters syndrome (BS) and Gitelmans syndrome (GS)lA maternal history of poly
19、hydramnios, 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. lBecause Cl- channels are expressed in both the basolateral membrane of LOH and D
20、CT, some patients with classical BS may have clinical profiles similar to that of GS. Bartters syndrome (BS) and Gitelmans syndrome (GS)lUnlike BS, non-steroid anti-inflammatory drugs (NSAIDs) are usually not effective in patients with GS due to the relatively normal urinary prostaglandin E2 excreti
21、on. Characteristic of Bartters syndrome (BS) and Gitelmans syndrome (GS) AR, autosomal recessiveSeSAME, seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance17-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，
22、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)lHyperchloremic metabolic acidosis involving both K+ depletion a
23、nd direct or indirect loss of HCO3lAn indirect estimate of NH4+ can be obtained from the urine anion gap (Na+K+Cl) or osmolal gap (measured-calculated urine osmolality)/2.lPositive 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.lIntravenous NaHCO3 loading at a rate of 2-3 mEq/kg/hour can be administered to separate proximal from distal RTA
