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.

Incidentes críticos en los docentes de enfermería: descubriendo una nueva identidad / Incidentes críticos em docentes de enfermagem: descobrindo uma nova identidade / Critical incidents in nursing academics: discovering a new identity

RESUMEN Objetivo: estudio cualitativo que siguió los principios de la teoría fundamentada con el fin de analizar la identidad profesional de docentes de enfermería por medio del análisis de incidentes críticos que más las desestabilizaban. Método: entrevistas semi-estructuradas fueron realizadas a siete enfermeras que actúan como docentes e investigadoras en una universidad privada de Barcelona. Resultados: el material empírico resultante fue organizado en dos categorías: caracterización de los incidentes críticos y reacción de las enfermeras frente a ellos. Conclusión: se concluye que la identidad profesional de estas enfermeras en el campo académico está aún en construcción y que la inexperiencia es el mayor obstáculo que enfrentan para gestionar los incidentes críticos en el trabajo docente. .

RESUMO Objetivo: estudo qualitativo que seguiu os princípios da teoria fundamentada em dados com o objetivo de analisar a identidade profissional de docentes de enfermagem por meio da análise de incidentes críticos que mais as desestabilizaram. Método: entrevistas semiestruturadas foram realizadas com sete enfermeiras que atuam como docentes e pesquisadoras em uma universidade privada de Barcelona. Resultados: o material empírico resultante foi organizado em duas categorias: caracterização dos incidentes críticos e reação das enfermeiras frente a eles. Conclusão: concluiu-se que identidade profissional dessas enfermeiras no campo acadêmico está ainda em construção e a que inexperiência é o maior obstáculo que enfrentam para gerenciar incidentes críticos no trabalho docente. .

ABSTRACT Objective: a qualitative study that followed the principles of the grounded theory in order to analyze the professional identity of nursing academics through the analysis of the most disturbing critical incidents. Method: semi-structured interviews were conducted with seven nurses who worked as professors and researchers in a private university in Barcelona. Results: the resulting empirical material was organized into two categories: characterization of critical incidents and responsiveness to the incident. Conclusion: the professional identity of nurses regarding the academic area is still under construction and inexperience is the major obstacle in the management of critical incidents in the teaching career. .

Resistência aos mineralocorticóides: pseudo-hipoaldosteronismo tipo 1 / Mineralocorticoid resistance: pseudohypoaldosteronism type 1

Pseudo-hipoaldosteronismo tipo 1 (PHA1) é uma doença genética rara, caracterizada por vômitos, desidratação, baixo ganho pôndero-estatural e perda urinária de sal no período neonatal. Indivíduos afetados apresentam hiponatremia, hipercalemia, aumento da atividade de renina plasmática e concentrações muito elevadas de aldosterona plasmática, secundárias a uma resistência renal ou sistêmica à aldosterona. A forma sistêmica do PHA1 é a mais grave, havendo necessidade de reposição de doses altas de NaCl. Os sintomas persistem por toda a vida. Mutações inativadoras nos genes codificadores das sub-unidades do canal de sódio sensível à amilorida (ENaC) em homozigose ou heterozigose composta são responsáveis pelo quadro clínico de PHA1 sistêmico. A forma renal do PHA1 tem apresentação clínica mais leve, com necessidade de suplementação de doses baixas de NaCl. Os sintomas regridem no final do primeiro ano de vida. Mutações inativadoras do gene do receptor do mineralocorticóide (MR) estão associadas à forma renal do PHA1 em várias famílias afetadas. O padrão de herança é autossômico dominante, entretanto casos esporádicos têm sido relatados. No presente trabalho, discutimos as ações e os mecanismos de ação da aldosterona, e os aspectos clínicos e fisiopatológicos envolvidos nas síndromes de resistência aos mineralocorticóides. Adicionalmente, os aspectos clínicos e moleculares de uma família brasileira com PHA1 secundário à mutação R947X no gene do MR são discutidos.

Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease characterized by neonatal renal salt wasting, vomiting, dehydration and failure to thrive. Affected patients present hyponatremia, hyperkalemia, associated with high levels of plasma renin and aldosterone resulting from a renal or systemic resistance to aldosterone. The systemic form of PHA1 results in a severe phenotype, and high doses of salt supplementation are necessary. The symptoms are life-long recurrent. This form is associated with autosomal recessive transmission. Homozygous or compound heterozygous loss of function mutations in the genes coding for the epithelial sodium channel (ENaC) subunities are responsible for this disease. The renal form of PHA1 results in a mild phenotype. Low doses of salt supplementation are required and usually the symptoms remit at the end of the first year of life. Heterozygous loss-of-function mutations in the mineralocorticoid receptor (MR) gene are associated with the renal form of PHA1 in the majority of the affected families but sporadic cases have been reported. In this review the mechanisms of aldosterone action and its effects are discussed. Additionally, clinical and molecular findings of a Brazilian family with the renal form of PHA1 caused by a nonsense mutation (R947X) in the MR gene are presented.