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.

Alterações hemogasométricas em equinos submetidos à distensão do cólon menor / Blood gas alterations in horses subjected to small colon distention

O objetivo do presente estudo foi avaliar a hemogasometria venosa de equinos com lesões isquêmicas induzidas experimentalmente no cólon menor. Foram utilizados oito equinos sadios, com idades entre cinco e oito anos, sem raça definida. Os animais foram submetidos à celiotomia e a quatro horas de obstrução intraluminal do cólon menor. Foram realizadas coletas de amostras de sangue imediatamente antes da indução anestésica (T0), no momento em que a anestesia foi estabilizada (T1), quatro horas após a obstrução intraluminal (T4), e, durante o pós-cirúrgico, as coletas foram realizadas em intervalos de 12 horas até completar 72 horas (T16, T28, T40, T52, T64 e T76). Notou-se em T4 alcalose metabólica, com compensação respiratória por meio da hipoventilação. Esse quadro de alcalose foi brando e transitório, retornando os valores normais para a espécie em T16, com 12 horas de desobstrução intestinal.(AU)

The objective of this study was to evaluate the blood gas analysis of venous blood of horses with experimentally induced ischemic lesions on the lower colon. Eight healthy horses were used, with ages between five and eight years, mixed breed. The animals were subjected to celiotomy and four hours of lower colonic intraluminal obstruction. The harvests were made with the blood samples immediately before induction of anesthesia (T0), when the anesthesia was stabilized (T1), 4 hours after the intraluminal obstruction (T4) and during postsurgical times were performed at intervals of 12 hours to complete 72 hours (T16, T28, T40, T52, T64 and T76). The occurrence of metabolic alkalosis on T4 with respiratory compensation by hypoventilation was noted, this alkalosis period was bland and transient, returning the normal values for the specie on T16, 12 hours after the intestinal obstruction.(AU)

Factores asociados a hiponatremia adquirida en la comunidad / Factors associated with community-acquired hyponatremia

El desarrollo de la hiponatremia en la comunidad es un aspecto poco estudiado, y su frecuencia y los factoresque la condicionan son poco conocidos. Objetivos: Estudiar los factores clínicos y de laboratorio asociados a la hiponatremia de pacientes incidentes en el servicio de emergencia de un hospital general. Material y métodos: Estudio de casos y controles. Los casos fueron pacientes con Na+ sérico5 mg/dl. Se contrastaron las variables edad, sexo, sistemas comprometidos, gravedad del paciente y valor de loselectrolitos; gases arteriales; urea y creatinina. El tamaño de muestra fue de 20 casos y 40 controles (confianza 95%, potencia 80% y OR 4)...

The prevalence and associated factors for developing hyponatremia in the community have not been adequately studied. Objectives: To study the clinical and laboratory factors associated with hyponatremia in patients attending the emergency room of a general hospital. Methods: A case-control was carried out, cases were patients with serum sodium values below 135 mEq/l at the time of admission to the emergency room of Hospital Cayetano Heredia and controls were patients admitted at the same time as cases with serum sodium values from 135 y 145 mEq/l. Patients with serum creatinine values >5 mg/dl were excluded...

Adult presentation of Bartter syndrome type IV with erythrocytosis / Apresentação tardia de síndrome de Bartter tipo IV com eritrocitose

Abstract Bartter syndrome comprises a group of rare autosomal-recessive salt-losing disorders with distinct phenotypes, but one unifying pathophysiology consisting of severe reductions of sodium reabsorption caused by mutations in five genes expressed in the thick ascending limb of Henle, coupled with increased urinary excretion of potassium and hydrogen, which leads to hypokalemic alkalosis. Bartter syndrome type IV, caused by loss-of-function mutations in barttin, a subunit of chloride channel CLC-Kb expressed in the kidney and inner ear, usually occurs in the antenatal-neonatal period. We report an unusual case of late onset presentation of Bartter syndrome IV and mild phenotype in a 20 years-old man who had hypokalemia, deafness, secondary hyperparathyroidism and erythrocytosis.

Resumo A síndrome de Bartter compreende um grupo raro de doenças autossômicas recessivas perdedoras de sal, decorrentes de mutações em genes expressos na porção ascendente espessa da alça de Henle, com fenótipos distintos, porém fisiopatogenia única, que consiste em redução severa da reabsorção de sódio, e aumento da excreção urinária de hidrogênio e potássio, levando à alcalose hipocalêmica. A síndrome de Bartter tipo IV, causada por mutações com perda de função da bartina, uma subunidade do canal de cloro CLC-Kb expressa no rim e ouvido interno, geralmente se apresenta nos períodos ante e neonatal. No presente relato, descreve-se um caso não usual de síndrome de Bartter tipo IV com apresentação tardia e fenótipo atenuado, diagnosticado por análise molecular, em um homem adulto de 20 anos que se apresentava com hipocalemia, surdez, hiperparatireoidismo secundário e eritrocitose.

Síndrome de Bartter: avaliação do desenvolvimento estatural e perfil metabólico / Bartter's syndrome: evaluation of statural growth and metabolic profile

OBJETIVO: A síndrome de Bartter é uma doença rara, porém uma das mais frequentes condições congênitas perdedoras de cloro. Este trabalho teve como objetivo relatar a evolução de dez pacientes com a síndrome. MÉTODOS: Estudo observacional, descritivo, realizado pela análise de prontuários médicos relatando o perfil metabólico, a depuração de creatinina, o estado nutricional e pôndero-estatural de dez pacientes atendidos no Serviço de Nefrologia da Universidade Federal de São Paulo com características clínico-laboratoriais da síndrome de Bartter, seguidos por um período médio de 43 meses (3-76 meses). Durante o acompanhamento, o tratamento consistiu na administração de suplemento de potássio (100 por cento), magnésio (60 por cento), anti-inflamatórios não hormonais (90 por cento), inibidores de enzima conversora de angiotensina (40 por cento) e espironolactona (50 por cento). A análise estatística constou da comparação dos dados da primeira e da última consulta, utilizando-se o teste de Wilcoxon. RESULTADOSs: Observou-se melhora dos valores absolutos dos itens avaliados e do desenvolvimento pôndero-estatural com a terapêutica empregada, porém apenas a calemia [mediana inicial 3,05mEqL e final 3,25mEqL (p=0,01)] e o escore Z de peso idade [mediana inicial -2,47 e final -1,35 (p=0,02)] apresentaram melhora significante. Dos dez pacientes estudados, dois apresentavam diminuição da depuração de creatinina com doença renal crônica estágio 2 no final do acompanhamento (ambos tinham iniciado o acompanhamento com depuração renal comprometida). CONCLUSÕES: Há necessidade da instituição terapêutica precoce para melhorar os níveis séricos dos eletrólitos e o estado nutricional dos pacientes acometidos, sem comprometer a depuração de creatinina.

OBJECTIVE: Bartter's syndrome is one of the most important inherited diseases that cause chloride leak. The objective of this study was to report the follow-up of ten patients with the syndrome. METHODS: This observational study was based on the review of medical charts reporting the metabolic features, creatinine clearance, nutritional and anthropometric assessment of ten patients with Bartter's syndrome followed at the Nephrology Service of the Universidade Federal de São Paulo, in their first and last medical appointments, after a mean follow-up period of 43 months (3-76 months). During the follow-up, the management included the administration of potassium (100 percent) and magnesium (60 percent) supplements, non-steroidal anti-inflammatory agents (90 percent), angiotensin-converting enzyme inhibitors (40 percent) and spironolactone (50 percent). Statistical analysis was performed comparing the results of first versus last clinical appointment by non-parametric Wilcoxon test. RESULTS: Improvement of serum electrolytes and statural growth after the treatment was observed but only serum potassium [3.05mEq/L versus 3.25 mEq/L (p=0.01)] and weigh-for-age Z-score [initial median -2.47 versus -1.35 (p=0.02)] improved significantly. Out of the ten patients studied, two presented decrease of creatinine clearance with chronic kidney disease at stage 2 at the end of the follow-up. These patients had already started the follow-up with decreased creatinine clearance. CONCLUSIONS: There is a need of early treatment of patients with Bartter's syndrome in order to improve their electrolytes and nutritional condition without compromising the creatinine clearance.

OBJETIVO: El síndrome de Bartter (SB) es una enfermedad rara, pero una de las más frecuentes condiciones congénitas perdedoras de cloro. Este trabajo tiene por objetivo relatar la evolución de diez pacientes con SB. MÉTODOS: Estudio observacional, descriptivo, obtenido mediante análisis de prontuarios médicos. Relata el perfil metabólico, la depuración de creatinina, el estado nutricio-nal y ponderoestatural de los diez pacientes atendidos en el ambulatorio de Tubulopatías de Universidade Federal de São Paulo con características clínico-laboratoriales de SB, seguidos por un periodo mediano de 43 meses (3-76 meses). Durante el seguimiento se practicó protocolo de tratamiento que consistió en la administración de suplemento de potasio (100 por ciento), magnesio (60 por ciento), anti-inflamatorios no hormonales (90 por ciento), inhibidores de enzima convertidora de angiotensina (40 por ciento) y espironolactona (50 por ciento). Se consideraron criterios de exclusión la presencia de alteraciones séricas y urinarias no compatibles con SB. El análisis estadístico constó de la comparación de datos de la primera y la última consulta, utilizándose la prueba de Wilcoxon. RESULTADOS: Se observó mejora numérica de los valores absolutos de los ítems evaluados y del desarrollo ponderoestatural con la terapéutica utilizada, pero solamente la calemia [mediana inicial 3,05mEq/L y final 3,25mEq/L (p=0,01)] y el escore Z de peso/edad [mediana inicial -2,47 y final 1,35 (p=0,02)] presentaron mejora significante. De los 10 pacien-tes estudiados, dos presentaban reducción de la depuración de creatinina con enfermedad renal crónica etapa 2 y en el final del seguimiento (ambos habían iniciado el seguimiento con depuración renal comprometida). CONCLUSIONES: Los datos enfatizan la necesidad de la ins-titución terapéutica precoz para mejorar los niveles séricos de los electrólitos y el estado nutricional, sin comprometer la depuración de creatinina.

Fibrosis quística que simula un síndrome de Bartter / Cystic fibrosis mimicking Bartter syndrome

La fibrosis quística es una enfermedad que se hereda como trastorno autosómico recesivo. La presentación clásica está caracterizada por enfermedad pulmonar crónica, deficiencia pancreática y concentraciones altas de electrolitos en sudor. En algunos pacientes la presentación puede ser monosíntomatica, por ejemplo, la depleción de electrolitos en sangre. El propósito de este informe es comunicar el caso de una lactante de 2 meses de edad diagnosticada de fibrosis quística, que inicialmente pareció ser un síndrome de Bartter. El motivo de ingreso fue un vómito, decaimiento y signos de deshidratación. Se realizó gasometría, estudio de electrolitos en sangre, determinación de concentración de electrolitos en la orina, prueba de electrolitos en sudor y estudio genético para fibrosis quística. La concentración de potasio (28 mEeq/L) hizo pensar en un síndrome de Bartter y se comenzó tratamiento con indometacina y cloruro de potasio; se normalizaron todos los parámetros. Dos meses después reingresó con deshidratación ligera por un vómito, trastornos mixtos del equilibrio ácido-base, hiponatremia, hipocloremia y ligera hiperpotasemia. Se realizaron electrolitos en sudor en 3 ocasiones y fueron positivos, y el estudio genético para fibrosis quística demostró una mutación delta F508.

Cystic fibrosis is a disease that is inherited as a recessive autosomal disorder. The classical presentation is characterized by chronic lung disease, pancreatic deficiency and high concentrations of electrolytes in sweat. In some patients, the presentation may be monosymptomatic as, for example, the depletion of electrolytes in blood. The objective of this paper is to report the case of a 2-months-old female infant with diagnosis of cystic fibrosis that initially seemed to be a Bartter syndrome. The reason to be admitted was vomit, dwindles and dehydration signs. Gasometry, study of electrolytes in blood, determination of concentration of electrolytes in urine, test of electrolytes in sweat and genetic study for cystic fibrosis were performed. The concentration of potassium (28 mEeq/L) made us think about Bartter syndrome, and treatment with indometacin and potassium chloride was indicated. All the parameters were normalized. Two months later, she was readmitted with mild dehydration caused by a vomit, mixed disorders of the acid-base balance, hyponatremia, hypochloremia and mild hyperpotassemia. Electrolytes were determined in sweat three times and they were positive. The genetic study for cystic fibrosis showed a delta F508 mutation.

Effects of acid-base imbalance on vascular reactivity

Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo) and those occurring within the intracellular space (pHi), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI2/cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

Hipopotassemia secundária a alcalose metabólica / Secondary hypopotassemia to metabolic alkalosis

A partir de um caso, freqüentemente encontrado na prática clínica, foram correlacionadas a hipopotassemia a alcalose metabólica (e näo as perdas digestivas de potássio). A interpretaçäo correta dos dados clínicos e laboratoriais permite o tratamento adequado da hipopotassemia.

Transepithelial pH gradients in cortical distal tubules during metabolic alkalosis

1. The cortical distal tubule of the rat kidney participates in the regulation of acid-base balance, showing bicarbonate reabsorption, secretion or absence of transport under different experimental conditions. In the present study, we measured differences in transepithelial pH using double ion-exchange resin/reference microelectrodes in control and alkalotic (chronic plus acute) male Wistar rats and in alkalotic rats receiving a K+ supplement in diet and infusion. 2. pH was measured in the tubule lumen during stationary microperfusion with 25 mM bicarbonate Ringer solution, and in peritubular vessels next to the perfused tubules. 3. Differences in transepithelial pH were 0.70 +/- 0.12 (N = 16) pH units in early distal tubules (ED) and 1.03 +/- 0.050 (N = 15) in late distal tubules LD) of control rats, 0.22 +/- 0.056 (N = 17) in ED and 0.25 +/- 0.050 (N = 20) in LD of alkalotic rats, and -0.02 +/- 0.039 (N = 24) in ED and -0.02 +/- 0.040 (N = 24) in LD of K(+)-supplemented alkalotic rats. 4. In control rats, the transepithelial potential difference (PD) (-8.9 +/- 1.45 mV (N = 16) in ED and -32.7 +/- 2.99 mV (N = 15) in LD) was not large enough to explain transepithelial H+ and HCO3- gradients, suggesting the presence of an active transport mechanism responsible for their maintenance. 5. The present data show that the cortical distal tubule is able to establish transepithelial pH (HCO3-) differences, that these differences are reduced by alkalosis and abolished by alkalosis plus K+ supplementation, and that, although inversion of pH gradients (evidence for bicarbonate secretion) was observed in individual tubules, this inversion was not significant in the groups studied

Evaluation of distal tubular function in aminoglycoside induced nephropathy

Acute metabolic acidosis potentiates the nephrotixicity of aminoglycosides by impairing the adequate excretion of ammonium and titratable acidity. The present study assesses distal tubular function after aminoglycoside administration in the rat. Two aminoglycosides, gentamicin and netilmicin were given to rats either in low doses equivalent to those used clinically (BG4 and BN5 groups) or in doses ten times higher (BG40 and BN50). The rats were subjected to acute metabolic alkalosis and the pCO2 of urine was continuously evaluated. the regression lines obtained by plotting the differences between urine and blood pCO2 as a function of urinary HCO3 in low dose models were simsilar to those obtained for the control group. However, the slopes obtained for BG40 and BN50 were significantly different from the control, suggesting an impairment of H+ secretion

The effect of alkalosis on the glucose-mediated insulin release by the rat

Efecto de la alcalosis sobre la secreción de insulina en la rata. Las ratas intactas que reciben una dosis de bicarbonato de sodio por vía gástrica entran en alcalosis por un período de tres horas durante el cual tienen bajos niveles plasmáticos de fosfato y calcio iónico y elevada excreción urinaria de cAMP, "clearance" de fosfato e incorporación de calcio del líquido extracelular al tejido pancreático, todos efectos conocidos del aumento de secreción de hormona paratiroidea (PTH). La secreción total de insulina en las dos horas siguientes a la estimulación con glucosa se halló significativamente aumentada en los animales alcalóticos intactos, respecto de sus controles simultáneos. La respuesta de las ratas alcalóticas paratiroidectomizadas, en cambio, sugirió agotamiento o inhibición de la secreción de insulina. Se propone la hipótesis de que la PTH, al aumentar la permeabilidad de las células beta del páncreas al calcio, compensa el efecto adverso, para la secreción de insulina, de la reducción de la concentración de calcio ionizado en el líquido extracelular que se observa en alcalosis

Efectos de la acidosis y alcalosis en retículo sarcoplásmico de corazón / The effect of acidosis and alcalosis in the sarcoplasmic reticulum of the heart

Se presentan los resultados del estudio de algunas funciones del retículo sarcoplásmico aislado del corazón de perro en condiciones acidosis y de alcalosis, en el rango de un pH de 6.0 a 7.8. El agua intravesicular medida a pH 6.0 es de 4.7 micronl por mg de proteína y disminuye un 15% hasta 4 micronl a pH 8.0 que se relaciona con un descenso en la turbidez de un 13.5%. Se encuentra un pH óptimo de 7.2 para la ATP asa dependiente de Ca**2+ con una actividad específica de 580 nmolas de ATP hidrolizado/min/mg de proteína. La ATP basal, dependiente de Mg**2+ es insensible a cambios de pH. Se alcanza una acumulación máxima de calcio de 45.1 + ou - 1.4 nmolas por mg de proteína entre pH 6.0 y 6.6. A pH mayor la cantidad de calcio acumulado disminuye progresivamente. La velocidad de transporte de calcio en estado estacionario muestra un pH óptimo de 6.7. Las constante cinéticas calculadas para el transporte de calcio muestran que la afinidad del retículo por este catión es máxima entre pH 6.87 y 7.02. La velocidad máxima del transporte disminuye progresivamente al pasar de pH 6.1 a 7.16. Cuando se cambia el pH de ácido a alcalino durante el proceso de transporte, se produce la salida del cacio acumulado en forma proporcional al incremento de pH. Este efecto es reversible. Se observa un desacople entre la acumulación de calcio y la hidrólisis de ATP a pH superiores a 6.6 debido al aumento en la velocidad de salida del calcio. Los valores encontrados de pK y de número de portones por mg de proteína que se disocian de grupos ionizables son 6.53 y 0.68 respectivamente para la ATP asa dependiente de calcio, 7.09 y 0.60 para el transporte de calcio y 7.41 y 0.39 para la salida de calcio. Concluimos que el transporte y la afinidad por el calcio del retículo sarcoplásmico cardiaco son óptimos entre pH 6.8 y 7.0, lo que corresponde con la zona de ph intracelular informado para el tejido cardiaco normal. Nuestros datos están de acuerdo con una disminución de la contractilidad durante la acidosis. Se propone una vía de salida de calcio en retículo que es sensible al pH y diferente de la bomba de calcio que es la única vía de entrada