Bartter's syndrome and Gitelman's syndrome: Pathogenesis, pathophysiology, and therapy

Bartter's syndrome was reported in 1962, and Gitelman's syndrome, which is subtype of Bartter's syndrome was described later. These syndromes are characterized by hypokalemia, hypochloremic metabolic alkalosis, normal to low blood pressure, although they show hyperreninemia, and hyperaldosteronemia. The cause of these diseases have been unexplained for a long time. Recently however, from 1996 to 2002, several causes have identified. Bartter's syndrome can occur due to a loss of function mutation in NKCC2, ROMK, CLC-Kb and barttin, or a gain of function mutation of calcium-sensing receptor. Gitelman's syndrome can occur due to a loss of function mutation in NCC. Different causes need different treatment and have different prognosis. In fact, we cannot examine all DNA sequences in regular hospitals. So it is our goal to make a clinical diagnostic standard to appropriate treatment.     

The syndrome of hypertension and hyperkalemia with normal GFR (Gordon's syndrome): is there increased proximal sodium reabsorption?

The syndrome of hypertension and hyperkalemia, hyperchloremic acidosis with normal glomerular filtration rate (Gordon's syndrome) is characterised by volume expansion, suppressed renin and reduced mineralocorticoid-induced renal clearance of potassium. The clinical and biochemical defects are aggravated by high salt diet and corrected by low salt diet, leading to the hypothesis of excessive sodium reabsorption in the nephron proximal to where aldosterone acts. In this study, we used lithium clearance as a marker of proximal sodium reabsorption in three patients with Gordon's syndrome, in order to further localise the site in the nephron of defective sodium handling. Fractional excretion of lithium was decreased, and absolute and fractional proximal reabsorption of sodium was increased compared to normal controls. In addition, absolute distal reabsorption of sodium was decreased, consistent with decreased mineralocorticoid activity. Fractional excretion of potassium was markedly decreased and did not rise with increased distal delivery of sodium during saline infusion. However, after severe dietary sodium restriction had elevated plasma aldosterone (lowering plasma potassium levels to normal), fractional excretion of potassium was raised by saline infusion. Reduced lithium clearance in patients with Gordon's syndrome supports the hypothesis of increased proximal sodium reabsorption in this condition.     

Bartter's and Gitelman's syndromes: from gene to clinic

Bartter's and Gitelman's syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis. Recently, investigators have been able to demonstrate mutations of six genes encoding several renal tubular transporters and ion channels that can be held responsible for Bartter's and Gitelman's syndromes. Neonatal Bartter's syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter's syndrome by mutations of ClC-Kb, Bartter's syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman's syndrome to mutations of NCCT and Bartter's syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR. We review the pathophysiology of these syndromes in relation to their clinical presentation.     

A comparison of Gordon's functional health patterns model and standard nursing care in symptomatic heart failure patients: A randomized controlled trial

BackgroundHeart failure (HF) is associated with poor quality of life and increased morbidity and mortality.AimThis study aimed to investigate effect of application of Gordon's functional health pattern (FHP) model in nursing care of symptomatic HF patients on quality of life, morbidity and mortality in the post-discharge 30-day.MethodsThis is a prospective randomized controlled study conducted in a single center. Experimental group received nursing care planned in accordance with Gordon's FHP model. 60 control and 60 experimental HF patients were included in the study. In the control group nursing care was given according to the standard protocol of the hospital whereas in the experimental group nursing care was given in accordance with Gordon's FHP model. Patients in both groups were followed up after discharge at 30th day.ResultsMean Minnesota Living with Heart Failure Questionnaire score improved significantly in the experimental group compared to the control group at 30th day (40.2 ± 23.5 vs 62.3 ± 22.9 respectively, p = 0.001). Seven patients (11.7%) in the experimental group and 17 patients (28.3%) in the control group were readmitted in the post discharge 30-day (p = 0.02). Kaplan-Meier survival curve analysis revealed significant difference in 30-day event free survival rates between groups (log-rank p = 0.31).ConclusionApplication of Gordon's FHP model in the nursing care of HF patients was associated with significantly improved quality of life, and reduced hospital readmission rates at 30th day. This was the only independent predictor of 30-day event free survival.     

How Bartter's and Gitelman's syndromes, and Dent's disease have provided important insights into the function of three renal chloride channels: ClC-Ka/b and ClC-5

Chloride channels are expressed in almost all cell membranes and are potentially involved in a wide variety of functions. The kidney expresses 8 of the 9 chloride channels of the ClC family that have been cloned so far to date in mammals. This review focuses on the pathophysiology of two renal disorders that have contributed recently to our understanding of the physiological role of chloride channels belonging to the ClC family. First are the related syndromes of Bartter's and Gitelman's, in which inactivating mutations of the genes encoding either of the ClC-Ks, or their regulatory beta-subunit barttin, have shown the important contribution of these chloride channels to renal tubular sodium and chloride (NaCl) transport along the loop of Henle and distal tubule. Second is the renal Fanconi syndrome known as Dent's disease, in which ClC-5 disruption has revealed the key role of this endosomal chloride channel in the megalin-mediated endocytotic pathway in the proximal tubule. The underlying pathophysiology of this inherited disorder demonstrates how ClC-5 is directly or indirectly required for the reabsorption of filtered low-molecular-weight proteins and bioactive peptides, also expression of membrane transporters, and clearance of calcium-based stone-forming crystals.     

Reye syndrome and Reye-like syndrome

Reye syndrome (RS) is an acute metabolic encephalopathy and hepatopathy affecting children and adolescents. Outbreaks of RS were common in United States until the early 1980s. However, after the abolition of salicylate (aspirin) therapy for infectious diseases such as influenza or varicella in patients under 18 years of age the incidence decreased. Now classical RS is rare and RS is considered a secondary mitochondrial disease. Reye-like syndrome (RLS), resulting from congenital errors of mitochondrial fatty oxidation, especially medium-chain acyl-CoA dehydrogenase deficiency, has increased due to progress in diagnostic techniques and methods after 1990. Diagnostic differentiation between RS and RLS is difficult because the end results of mitochondrial dysfunction in RS and RLS may be similar.     

多囊卵巢综合征与代谢综合征关系的研究

目的 探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)、胰岛素抵抗及代谢综合征(metabolic syndrome,MS)的关系.方法 临床收集101例PCOS患者的血糖、胰岛素、血脂、性激素等指标,按稳态模型(HOMA)计算胰岛素抵抗指数(HOMA-IR),依照4个不同的标准--美国国家胆固醇教育计划成人治疗方案第三次报告(ATPⅢ)(2005年)、国际糖尿病联盟(IDF)(2005年)、中华医学会糖尿病学分会(CDS)(2004年)和<中国成人血脂异常防治指南>制定联合委员会(JCDCG)(2007年),计算PCOS患者中MS的发生率.并将患者分为PCOS伴MS和PCOS不伴MS两组就相关指标进行比较.结果 ①根据ATPⅢ(2005)、IDF(2005)、CDS(2004)、JCDCG(2007)MS诊断标准,PCOS中MS的发病率分别为45.5%、43.6%、31.7%、32.7%.②PCOS伴MS和PCOS不伴MS的患者临床指标的比较:在年龄、腰围、腰臀比(WHR)、收缩压、空腹血糖(FBG)、胰岛分泌指数(HOMA-β)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、黄体激素(LH)、卵泡刺激素(FSH)、雌二醇(E2)、睾酮(T)、泌乳素(PRL)方面,两组差异无统计学意义;在体质量指数(BMI)、舒张压、餐后2小时血糖(PBG)、空腹胰岛素、餐后2小时胰岛素、甘油三酯(TG)、血尿酸方面,PCOS伴MS较PCOS不伴MS显著升高,在HOMA-IR则显著降低,差异有统计学意义.结论 按照MS的4个定义--ATP Ⅲ(2005)、IDF(2005)、CDS(2004)、JCDCG(2007)标准,PCOS患者中均有较高的MS的患病率.PCOS伴MS患者存在较明显的胰岛素抵抗,肥胖尤其是腹型肥胖与MS、胰岛素抵抗密切相关.     

胰岛素抵抗综合征与代谢综合征的异同及临床意义

胰岛素抵抗综合征(IRS)和代谢综合征(MS)一直是临床关注的热点。近年来,随着对IRS和MS的深入研究,人们对两者间的内在联系及其病理生理意义有了新的理解,IRS与MS既有内在联系又     

Leigh综合症和Leigh样综合症研究进展

Leigh综合症是一种破坏性很大的神经系统变性疾病,是婴幼儿最常见的线粒体疾病.本文对Leigh综合症和Leigh样综合症在遗传背景、致病力、诊断、治疗和预后方面的最新进展进行综述.