Regulation of kidney on potassium balance and its clinical significance / 生理学报

Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na+ by the epithelial Na+ channel (ENaC) located at the apical membrane of principal cells. When Na+ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K+ efflux, H+ efflux, and Cl- influx are the 3 pathways that respond to Na+ influx, that is, all these 3 pathways are coupled to Na+ influx. In general, Na+ influx is equal to the sum of K+ efflux, H+ efflux, and Cl- influx. Therefore, any alteration in Na+ influx, H+ efflux, or Cl- influx can affect K+ efflux, thereby affecting the renal K+ excretion. Firstly, Na+ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na+ reabsorption, K+ excretion, as well as H+ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na+ and decreased excretion of both K+ and H+, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na+ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na+-K+-2Cl- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na+ by ENaC at the collecting duct, as well as increased excretion of K+ and H+, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H+ decreases. Both above conditions can lead to increased K+ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.

Acidose tubular renal tipo IV no pronto atendimento / Renal tubular acidosis type IV in emergency medical services

No Hospital de Base de São José do Rio Preto, uma paciente com diabetes melito tipo 2, apresentando quadro de acidose metabólica, foi tratada na emergência da clínica médica. Foi seguido inicialmente protocolo de cetoacidose diabética. Após um dia sem melhora clínica, com a hipótese diagnóstica de acidose tubular renal tipo IV, confirmada pela acidose metabólica hipercalêmica e hiperclorêmica, foi optado por introduzir fludrocortisona no tratamento. Devido à melhora clínica e laboratorial fechou-se o diagnóstico e a paciente encontra-se em acompanhamento no ambulatório.

At the Hospital de Base hospital in São José do Rio Preto, a type II diabetic patient presenting metabolic acidosis was treated at the internal medicine ER. Initially the diabetic ketoacidosis treatment protocol was followed. Due to no improvement after one day of treatment, the diagnostic hypothesis of renal tubular acidosis type IV was confirmed by the hyperkalemic and hyperchloremic metabolic acidosis. We treated the patient with fludrocortisone. Due to clinical recovery and improvement of laboratory results, the patient was discharged and is now an outpatient in our institution.

Influência do veículo na eficácia da reposição de potássio em ratos hipocalêmicos / Vehicle influence on potassium replacement effectiveness in hypokalemic rats

INTRODUÇÃO: Pacientes após cirurgia cardíaca são comumente tratados com diuréticos para controle de volume plasmático. A preocupação de distúrbios hipocalêmicos em adultos antes, durante ou após a cirurgia já foi ressaltada anteriormente, visto o risco de arritmias cardíacas. Clinicamente, a diluição da solução de potássio (K+) para administração por via intravenosa, em situações que requerem a sua reposição é realizada utilizando-se soro fisiológico (SF) ao invés de soro glicosado 5 por cento (SG5 por cento), possivelmente em vista de poder ocorrer estimulação da secreção de insulina, que interferiria sobre a qualidade da reposição de K+. Porém, não está comprovado experimentalmente se o SF e SG5 por cento poderiam realmente interferir na qualidade da reposição de potássio em ratos com hipocalemia. OBJETIVO: Analisar a influência da reposição de K+ diluído em diferentes veículos sobre as concentrações plasmáticas de K+([K+]p) em ratos submetidos a hipocalemia induzida por furosemida. MÉTODOS: Ratos Wistar adultos foram divididos em quatro grupos: K++SF, K++SG, SF e SG. Foi realizada a canulação da veia jugular para reposição e da veia femoral para coleta de sangue. O diurético furosemida na dose de 50mg/kg foi usado para induzir hipocalemia, foi analisado nível plasmático de potássio 24 h antes da injeção de furosemida, 24 h pós-indução e 30 minutos pós-reposição. RESULTADOS: Os níveis da [K+] pós-injeção de furosemida sofreram redução, comparado aos valores basais (pré-furosemida) em todos os grupos. Entretanto, os níveis [K+] retornaram aos valores basais tanto nos grupos que receberam K++SF ou K++SG, o que não foi observado nos grupos que receberam apenas SF e SG. Quanto ao Na+ plasmático, somente o grupo K+SF apresentou aumento após reposição. CONCLUSÃO: A reposição de K+ diluído tanto em SF quanto SG parece não afetar a qualidade da reposição de K+ plasmático em ratos

INTRODUCTION: Patients who undergo cardiac surgery are commonly treated with diuretic therapy for the management of volume overload. The concern of hypokalemia important in the adult population submitted to cardiac surgery has been described. Intravenous potassium (K+) replacement dilution is only recommended with sodium chloride 0.9 percent solution (SF0.9 percent), likely due to the putative effects of glucose solution 5 percent (SG5 percent) on insulin secretion, which influence K+ replacement quality. However, it is not yet experimentally proved the influence of SF0.9 percent and SG5 percent on K+ replacement quality. Objectives: To evaluate the effects of different vehicles of K+ replacement on blood K+ levels in furosemide hypokalemic rats. METHODS: Male Wistar rats divided into four groups: K+SF, K+SG, SF and SG. Jugular vein cannulation for K+ replacement and femoral vein cannulation for blood analysis. Furosemide (50mg/kg) to induce hypokalemia. We prepared the following solutions: vehicle 1.6mL (SF0.9 percent or SG5 percent) + 0.4 mL de K+ (19.1 percent) and for control groups only vehicle 2 mL. Furosemide (50 mg/kg) was used to induce hypokalaemia, it was analyzed potassium plasmatic levels 24 hours before furosemide injection, 24 hours after furosemide injection and 30 minutes after post-replacement. RESULTS: There was no significative difference in blood K+ levels before furosemide administration, after hypokalemic induction and after K+ replacement among all groups. Only SF+K presented blood Na+ levels increaseafter K+ replacement (P<0.05). CONCLUSION: K+ replacement in different vehicles did not affect blood K+ levels in rats

A Korean Family of Hypokalemic Periodic Paralysis with Mutation in a Voltage-gated Calcium Channel (R1239G)

Hypokalemic periodic paralysis (HOPP) is a rare disease characterized by reversible attacks of muscle weakness accompanied by episodic hypokalemia. Recent molecular work has revealed that the majority of familial HOPP is due to mutations in a skeletal muscle voltage-dependent calcium-channel: the dihydropyridine receptor. We report a 13-yr old boy with HOPP from a family in which 6 members are affected in three generations. Genetic examination identified a nucleotide 3705 C to G mutation in exon 30 of the calcium channel gene, CACNA1S. This mutation predicts a codon change from arginine to glycine at the amino acid position #1239 (R1239G). Among the three known mutations of the CACNA1S gene, the R1239G mutation was rarely reported. This boy and the other family members who did not respond to acetazolamide, showed a marked improvement of the paralytic symptoms after spironolactone treatment.

Parálisis periódica hipokalémica: a propósito de dos casos / Hipokalemic periodic paralysis: apropos of 2 cases

La parálisis periódica hipocalémica es una entidad poco frecuente, con un aparente rasgo genético, que reconoce una variada lista etiológica, dependiendo de las mismas la terapéutica a instaurar. Debido a la gravedad de la presentación clínica y a la restitución ad integrum luego del adecuado tratamiento del desorden electrolítico, es que se presentan los siguientes casos para su discusión.

Memorias del V curso internacional: avances en enfermedad diarreíca y desequilibrio hidroelectrolítico, 5 / Memories of the V international course: advances in diarrheic disease and hydroelectrolitical unbalance

La alcalosis metabólica es un aumento primario del bicarbonato del plasma que se produce por una ruptura de la alineación bicarbonato/presión de anhídrido carbónico con disminución en las concentraciones de hidrogeniones y aumento del pH del plasma. Se caracteriza por presentar el pH, el bicarbonato del plasma y la presión de anhídrido carbónico elevados en sangre arterial acompañada, normalmente, de hipokalemia e hipocloremia. Las causas que provocan la alcalosis metabólica se clasifican en cuatro grupos: 1. Por administración contínua de alimentos. 2. Por la respuesta de la alcalosis hacia los cloruros. 3. Por resistencia de la alcalosis hacia los cloruros y 4. Otras causas diferentes de los grupos anteriores pero que producen alcalosis metabólica. El cuadro clínico que presenta el paciente se caracteriza por la presencia de vómitos abundantes, generalmente en lactantes, con ausencia de bilis y acompañados de respiraciones lentas y superficiales, en ocasiones se presentan crisis de apnea o tambien el paciente manifiesta debilidad y decaimiento con calambres, pudiendo, además, mostrar signos clínicos de tetania. Además hay irritabilidad y signos de hipotasemia. Para el diagnóstico de la alcalosis metabolica además de la observación del vómito, se realizan estudios de: Gasometría, ionograma, pH en la orina y determinación de cloro y potasio en la orina. El método clínico para determinar el tratamiento consiste en detrminar primero la causa