Milk-Alkali Syndrome: A Century Old Cause of Resurgence of Severe Hypercalcemia Due to Excessive Use of Calcium Supplements

The milk-alkali syndrome (MAS) is characterized by a triad of elevated calcium levels, metabolic alkalosis and acute kidney injury that commonly occurs due to the combined intake of large amounts of calcium and absorbable alkali. The syndrome can have an acute onset with the rapid development of hypercalcemia and, if left untreated, may result in acute renal failure and metastatic calcification. An increased number of cases of MAS have recently been reported. This is likely due to the common use of over the counter (OTC) preparations of calcium for preventing and treating osteoporosis in postmenopausal women. Herein, we report a case of severe hypercalcemia due to prolonged intake of calcium carbonate supplements in the absence of any alkali.

El regulador de transmembrana de fibrosis quística (CFTR) disfuncional y sus efectos extrapulmonares / The dysfunction of transmembrane regulator in cystic fibrosis (CFTR) and its extrapulmonary effects

El daño del regulador de transmembrana de fibrosis quística (CFTR) puede causar una enfermedad grave fuera de los pulmones. El canal de cloruro (Cl-) ha sido el más estudiado, sin embargo, el bicarbonato (HCO3 -) tiene un rol muy importante en el comportamiento de las secreciones y la inflamación secundaria. El hecho de que CFTR funcione no sólo como un canal de Cl- sino también de HCO3- es un campo para la investigación y el desarrollo de fármacos para pacientes con daño genético o adquirido, este último frecuente en la población general. Algunos moduladores de CFTR pueden tener un beneficio terapéutico en el tratamiento de pancreatitis en ambas situaciones. La disfunción del CFTR a nivel renal puede resultar excepcionalmente en alcalosis metabólica y reducción del impulso ventilatorio. Hasta la fecha no está claro cuales serian sus efectos en los sistemas gastrointestinal y hepatobiliar.

Transmembrane regulator in cystic fibrosis (CFTR) can cause severe disease outside of the lungs. The chloride channel (Cl-) has been the most studied, however bicarbonate (HCO3 -) has a very important role in the behavior of secretions and secondary inflammation. The fact that CFTR works not only as a Cl- channel but also as an HCO3- channel is a field for research and development of drugs for patients with genetic or acquired damage, the latter frequent in the general population. Some CFTR modulators may have a therapeutic benefit in the treatment of pancreatitis in both situations. CFTR dysfunction at the renal level can exceptionally result in metabolic alkalosis and reduced ventilatory drive. To date it is not clear what its effects on the gastrointestinal and hepatobiliary systems would be.

Alteraciones del estado ácido básico en pacientes adultos con insuficiencia renal crónica / Acid-base status alterations in adult patients with chronic renal failure

RESUMEN Introducción: el portador de insuficiencia renal crónica puede presentar diversas alteraciones del estado ácido básico, siendo la acidosis metabólica la más frecuente. Objetivos: describir las características demográficas y clínicas y las alteraciones del estado ácido básico de pacientes adultos que ingresan con insuficiencia renal crónica en dos centros hospitalarios del Paraguay. Metodología: se aplicó un diseño observacional, descriptivo, transversal. Se incluyó a sujetos adultos de ambos sexos, portadores de insuficiencia renal crónica, que acudieron al Hospital Nacional (Itauguá) y Hospital Militar (Asunción) entre abril y noviembre del 2021. Se midieron variables antropométricas, clínicas y laboratoriales al ingreso. Los datos se sometieron a estadística descriptiva con el programa Epi Info 7™. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este, Paraguay. Resultados: se incluyó a 148 sujetos, siendo 78 (52,7 %) varones con edad media 58 ± 16 años y 70 (47,3 %) mujeres con edad media 54 ± 17 años. Las etiologías más frecuentes de la insuficiencia renal crónica fueron la diabetes mellitus e hipertensión arterial (44,5 %). Se detectó 12 sujetos (8,1 %) con gasometría normal. La alteración del estado ácido básico más frecuente fue la acidosis metabólica (87,2 %), predominando en este grupo los casos con brecha aniónica normal. Conclusiones: las alteraciones del estado ácido básico predominantes en pacientes con insuficiencia renal crónica fue la acidosis metabólica con brecha aniónica normal. Se sugiere aplicar los cálculos de los mecanismos compensadores para llegar al diagnóstico certero de estas alteraciones metabólicas.

ABSTRACT Introduction: the carrier of chronic renal failure can present various alterations of the basic acid state, being the metabolic acidosis the most frequent. Objectives: to describe the demographic and clinical characteristics and alterations in the acid-base status of adult patients admitted with chronic renal failure in two hospitals in Paraguay. Methodology: an observational, descriptive, cross-sectional design was applied. Adult subjects of both sexes, carriers of chronic renal failure, who attended the National Hospital (Itauguá) and the Military Hospital (Asunción) between April and November 2021 were included. Anthropometric, clinical and laboratory variables were measured at admission. The data was submitted to descriptive statistics with the Epi Info 7™ program. The study was approved by the Ethics Committee of the Universidad Privada del Este, Paraguay. Results: 148 subjects were included, being 78 (52.7 %) men with a mean age of 58 ± 16 years and 70 (47.3 %) women with a mean age of 54 ± 17 years. The most frequent etiologies of chronic renal failure were diabetes mellitus and arterial hypertension (44.5 %). 12 subjects (8.1 %) with normal blood gases were detected. The most frequent alteration of the acid-base status was metabolic acidosis (87.2 %), with cases with normal anion gap predominating in this group. Conclusions: the predominant acid-base status alterations in patients with chronic renal failure was metabolic acidosis with normal anion gap. It is suggested to apply the calculations of the compensatory mechanisms to arrive at the accurate diagnosis of these metabolic alterations.

Alcalosis respiratoria grave, la transformación de un cuadro funcional en orgánico. Caso clínico

Severe respiratory alkalosis is a life-threatening condition, as it induces hypo- calcaemia and extreme adrenergic sensitivity leading to cerebral and myocardial vasoconstriction. We report a 37-year-old woman with previous consultations for a conversion disorder. While she was infected with SARS-CoV-2 (without pulmonary involvement), she consulted in the emergency room due to panic attacks. On admission, she developed a new conversion crisis with progressive clinical deterioration, hyperventilation, and severe respiratory alkalosis (pH 7.68, Bicarbonate 11.8 mEq/L and PaCO2 10 mmHg). Clinically, she was in a coma, with respiratory and heart rates 55 and 180 per min, a blood pressure of 140/90 mmHg, impaired perfusion (generalized lividity, distal coldness, and severe skin mottling) and tetany. She also had electrocardiographic changes and high troponin levels suggestive of ischemia, and hyperlactatemia. She was managed in the hospital with intravenous benzodiazepines. The clinical and laboratory manifestations resolved quickly, without the need for invasive measures and without systemic repercussions.

Sistemática para el manejo del equilibrio ácido-base en pacientes graves / Systemization for the management of acid-base balance in seriously ill patients

Introducción: Las alteraciones del equilibrio ácido-base pueden ser de carácter primario. En la mayoría de los casos dependen de la complicación de una enfermedad preexistente. La frecuencia de estos trastornos es elevada, especialmente, en enfermos hospitalizados en las unidades de atención al paciente grave. Su aparición conlleva implicaciones pronósticas significativas. Objetivo: Sistematizar sobre el estado actual del manejo del equilibrio ácido-base. Método: Se realizó una revisión bibliográfica en la que se utilizaron las herramientas del método científico. Se examinó toda la bibliografía disponible publicada en los últimos cinco años y así, elaborar una síntesis crítica, acorde al criterio y las competencias de los autores sobre la temática. Resultados: Se expone la importancia de la evaluación clínica, que unida a los niveles de PCO2, y de exceso o déficit de bases en una gasometría arterial, permiten identificar el trastorno ácido base existente. Igualmente, se destaca que el CO2 tiene una función clave en el control de la ventilación, así como las modificaciones que produce al flujo sanguíneo cerebral, el pH y el tono adrenérgico. Otro aspecto importante fue la reciente práctica clínica de la "hipercapnia permisiva" para reducir el metabolismo tisular y de esta manera, mejorar la función del surfactante e impedir la nitración de las proteínas. Conclusiones: El manejo de los desequilibrios ácido-base debe ser del dominio de todos los profesionales vinculados a la asistencia médica, pues el retraso de su diagnóstico puede empeorar la evolución y el pronóstico de los pacientes graves(AU)

Introduction: Acid-base balance alterations can be of a primary nature. In most cases, they depend on the complication of a pre-existing disease. The frequency of these disorders is high, especially in patients hospitalized in critical care units. Its appearance carries significant prognostic implications. Objective: To systematize the current state of acid-base balance management. Method: A bibliographic review was carried out, for which the tools of the scientific method were used. All the available bibliography, published in the last five years, was examined; thus, a critical synthesis was prepared, according to the criteria and competences of the authors regarding the subject. Results: The importance of the clinical evaluation is exposed, which, together with PCO2 levels as well as excess or deficit of bases in an arterial blood gas, allow to identify the existing acid-base disorder. Likewise, it is highlighted that CO2 has a key function in ventilation control, together with the modifications it produces on cerebral blood flow, pH and adrenergic tone. Another important aspect was the recent clinical practice of "permissive hypercapnia" to reduce tissue metabolism and thus improve surfactant function and prevent protein nitration. Conclusions: The management of acid-base imbalances should be mastered by all professionals associated to medical care, since any delay in its diagnosis can worsen the evolution and prognosis of seriously ill patients(AU)

Recovery from severe metabolic alkalosis with acute kidney injury due to gastric cancer: a case report / Journal of Rural Medicine

Objective: Most cases of severe metabolic alkalosis have many causes that may result in renal failure and death. Therefore, these should be treated promptly for successful recovery.Patient: A 61-year-old man was hospitalized due to an acute kidney injury (creatinine level of 4.36 mg/dL) after a 3-month history of anorexia and recurrent vomiting. He had been treated for tuberculosis in the past.Results: Blood gas analysis revealed severe metabolic alkalosis with pH=7.66, HCO3=94 mmol/L, and pCO2=82.0 mmHg. Routine biochemical examination revealed severe hypokalemia (K 2.9 mEq/L) that was associated with prolonged QTc interval (0.52 seconds) on the electrocardiogram. Gastrofiberscopic examination also revealed severe stenosis and ulcerated scarring of the gastric pylorus and severe esophagitis. Intravenous hydration and correction of hypokalemia improved renal function and resolved metabolic alkalosis. An investigation that was repeated after 6 days revealed a creatinine level of 1.58 mg/dL, pH=7.47, HCO3=23.4 mmol/L, K=3.6 mEq/L, and QTc of 0.45 seconds. The patient underwent gastrectomy and adenocarcinoma was observed.Conclusion: We described a resolved case of severe metabolic alkalosis and acute kidney injury in a rural medical setting following conservative management.

Diagnóstico de síndrome de Gitelman en paciente con condrocalcinosis / Diagnosis of gitelman syndrome in patient with condrocalcinosis

RESUMEN Introducción: El síndrome de Gitelman es una tubulopatía caracterizada por alcalosis metabólica hipopotasémica, hipomagnesemia e hipocalciuria. Sus efectos musculoesqueléticos son comunes, pudiendo provocar desarrollo de condrocalcinosis. Caso clínico: Paciente con condrocalcinosis de larga data asociada a hipomagnesemia crónica en tratamiento con calcio y magnesio. Tras la suspensión del tratamiento debido a una intervención quirúrgica presentó debilidad generalizada, alcalosis metabólica, hipopotasemia, hipomagnesemia e hipocalciuria con diagnóstico final de síndrome de Gitelman. Tras la instauración de tratamiento, mejoró clínica y analíticamente manteniendo cifras iónicas estables. Discusión y conclusiones: Resulta fundamental un adecuado diagnóstico de este tipo de tubulopatías, ya que un tratamiento adecuado evita complicaciones asociadas.

ABSTRACT Introduction: Gitelman syndrome is a renal tubule disease that involves hypokalaemic metabolic alkalosis, hypomagnesaemia and hypocalciuria. The musculoskeletal effects of Gitelman syndrome are common, including the development of chondrocalcinosis. Clinical case: A female patient with long-standing chondrocalcinosis associated with chronic hypomagnesaemia on treatment with calcium and magnesium. After the suspension of the treatment due to surgery, she presented with a generalised weakness, metabolic alkalosis, hypokalaemia, hypomagnesaemia and hypocalciuria, with final diagnosis of Gitelman syndrome. After re-introducing the treatment, she improved clinically, with electrolytes remaining stable. Discussion and conclusions: A proper diagnosis of this type of tubular diseases is essential because an adequate treatment avoids associated complications.

Distúrbios ácido-base nas doenças hepáticas / Acid-base disorders in liver diseases

O objetivo deste artigo foi abordar as controvérsias científicas acerca dos distúrbios ácido-base nas doenças hepáticas. Nos estágios avançados da doença hepática, os distúrbios ácido-base atuam de forma complexa, comprometendo a qualidade de vida do paciente e desafiando o manejo clínico. A literatura apresenta a alcalose respiratória como uma das principais alterações, porém há uma longa discussão sobre o mecanismo fisiopatológico; em especial, citam-se a hipóxia, a hipocapnia e o nível de progesterona. Nas desordens metabólicas, com destaque para a acidose, os estudos apontam principalmente o lactato, os unmeasured ions ou íons não medidos e as alterações hidroeletrolíticas, mas cada componente desse sobressai-se dependendo da fase da doença estudada, compensada ou descompensada. As controvérsias dos distúrbios ácido-base nas doenças hepáticas devem-se ora à complexidade da fisiopatologia da própria doença, ora à necessidade de mais estudos esclarecedores.

The aim of this study is to address the scientific controversy about acid-base disorders in liver diseases. In the end stage of liver diseases, the acid-base disorder has a complex performance, impairing the patient's quality of life and challenging the clinic management. Although the literature shows respiratory alkalosis as one of the main alterations, there is a long discussion about the pathophysiological mechanism, specially regarding hypoxia, hypocapnia, and progesterone level. In metabolic disorders, especially acidosis, the studies mainly indicate the lactate, unmeasured ions, and hydroelectrolytic alterations, but, depending on the disease phase, either compensated or decompensated, each element has a particular action. The controversy about acid-base disorders in liver diseases is associated with the complexity of this condition, as well as with the necessity of more specialized research.

Acute effect of sodium bicarbonate supplementation on the performance during CrossFit® training

Abstract Aim: To verify the acute effect of sodium bicarbonate (NaHCO3) supplementation on performance during CrossFit® workout. Methods: Nine experienced males (30.8 ± 3.5 years; 84.4 ± 9.5 kg; 177.5 ± 4.03 cm; 2.2 ± 1.0 years) in CrossFit® participated in this study. They were allocated to two conditions: a) supplementation with 0.3 g.kg-1 of body weight of NaHCO3 and b) supplementation with 0.045 g.kg-1 of body weight of sodium chloride (NaCl). Blood lactate was analyzed at two different moments: before (lac-pre) and after the training protocol (lac-post). The heart rate (HR) and the rating of perceived exertion (RPE) were also collected every two minutes during the execution of the training protocol, and the RPE was also collected after it was finished. At the end of the training protocol, a questionnaire to measure gastrointestinal side effects (GSE) was answered by the participants. Repetitions performed in the training protocol was computed to evaluate the performance during the workout. Results: The results showed that there were no differences found when comparing the conditions for all parameters. HR and RPE were different in the first few minutes (< 4-6 minutes) when compared to the final minutes (> 14 minutes) of the workout. The area under the curve of HR and RPE was significantly lower in the NaHCO3 condition. Conclusion: Acute NaHCO3 supplementation did not improve performance during workout 'Cindy' in experienced men. Supplementation also did not alter hemodynamic and perceptual parameters, nor did it cause any GSE. However, responses as a function of time were reduced with NaHCO3 supplementation.

Síndrome de Bartter: una tubulopatía infrecuente de inicio antenatal / Bartter syndrome: an infrequent tubulopathy of prenatal onset

INTRODUCCIÓN: Síndrome de Bartter (SB) es una tubulopatía hereditaria, poco frecuente que tiene dos formas de presentación, forma grave de inicio antenatal (Bartter neonatal) y forma de aparición más tardía (Bartter clásico). En su forma antenatal se manifiesta con poliuria fetal, polihidroamnios de inicio precoz y severo, parto prematuro secundario y restricción de crecimiento intrauterino. La etapa postnatal presenta episodios recurrentes de deshidratación y desbalance electrolítico que pue den comprometer la sobrevida del paciente. OBJETIVO: Comunicar un caso de SB neonatal y presentar una revisión de la literatura en esta patología. CASO CLÍNICO: Prematuro 35 semanas, con antecedente de severo polihidroamnios diagnosticado a las 27 semanas de gestación, sin causa aparente. Desde su nacimiento evolucionó con poliuria y alcalosis metabólica hipokalémica haciendo plantear, en primera semana de vida, diagnóstico de Síndrome de Bartter neonatal. El laboratorio confirmó per didas urinarias de electrólitos. Fue manejado con balance hídrico estricto y suplementación de sodio y potasio, logrando estabilizar peso y desbalance electrolítico. Se mantiene en control nefrológico, con suplementación de gluconato de potasio y cloruro de sodio. Se agregó ibuprofeno al cuarto mes como parte del tratamiento. Al séptimo mes de vida, ecografía renal demostró nefrocalcinosis. Al año de vida se evidenció hipoacusia sensorioneural profunda requiriendo implante coclear. CONCLUSIÓN: Presencia de polihidroamnios severo de aparición temprana sin causa identificada debe hacer sospechar SB, que aun siendo infrecuente determina graves alteraciones hidroelectrolíticas y debe ser iniciado su tratamiento precozmente.

INTRODUCTION: Bartter syndrome (BS) is a rare inherited tubulopathy that has two presentation forms, the first one is a severe form of antenatal onset (neonatal Bartter) and the second one is a later on set form during the first years of life (classic Bartter). In the antenatal form, it manifests with fetal polyuria, polyhydramnios of early and severe onset, premature delivery, and intrauterine growth restriction. In the postnatal stage, it presents recurrent episodes of dehydration and electrolyte im balance that can compromise the survival of the patient. OBJECTIVE: To report a clinical case of neo natal BS and a review of the literature. CLINICAL CASE: Premature newborn of 35 weeks of gestation with history of severe polyhydramnios diagnosed at 27 weeks of gestation, without apparent cause. From birth, the patient presented polyuria and hypokalemic metabolic alkalosis making a diagnosis of Neonatal Bartter Syndrome in the first week of life. Laboratory tests confirmed urinary electrolyte losses. The patient was treated with strict water balance and sodium and potassium supplementa tion, achieving weight and electrolyte imbalance stabilization. The patient remains in control in the nephrology unit, with potassium gluconate and sodium chloride supplementation. At the fourth month, ibuprofen was added as part of treatment. At the seventh month of life, renal ultrasound showed nephrocalcinosis. At one year of life, profound sensorineural hearing loss was observed re quiring a cochlear implant. CONCLUSION: The presence of severe polyhydramnios of early onset with no identified cause should lead to suspicion of neonatal BS which even when infrequent determines severe hydroelectrolytic alterations and should be treated early.

Sodium bicarbonate supplementation improves performance in isometric fatigue protocol / A suplementação de bicarbonato de sódio melhora o desempenho em protocolo de fadiga isométrico / La suplementación de bicarbonato de sodio mejora el desempeño en protocolo de fatiga isométrico

ABSTRACT Introduction: Although sodium bicarbonate (NaHCO3) supplementation has been shown to decrease fatigue and improve high-intensity exercise performance, the effects on maintenance of isometric contractions are not clear. Objective: To investigate the effect of NaHCO3 on the performance of individuals subjected to a fatigue protocol in an isometric exercise on the isokinetic dynamometer. Methods: Participants were 12 men in a randomized, double-blind, crossover, placebo-controlled trial. Sixteen minutes after the intake of 0.3 g/kg of body mass of NaHCO3 or placebo, the participants performed an isometric fatigue protocol of right knee extension exercises during eight minutes at 70% of maximum voluntary isometric contraction. The fatigue indicator was the time point at which torque was reduced to 50% of the initial value. The length of resistance was assessed by maintaining the task over 50% of the initial torque. Lactate/blood pH concentrations and rate of perceived exertion (RPE) and pain (RPP) indexes were analyzed. The RPE of the session was evaluated 30 minutes after the test. Results: Blood pH was higher in pre-protocol and in the fatigue indicator after NaHCO3 intake, as were the blood lactate concentrations in the fatigue indicator and at the end of the protocol (p<0.001). NaHCO3 supplementation increased the time to fatigue and lessened the rate of decline of isometric peak torque at the end of the protocol (p<0.001). RPE and RPP were smaller at the end of the protocol in the NaHCO3 condition, and the RPE of the session was diminished (p<0.001). Conclusion: NaHCO3 supplementation enhances steady isometric contraction performance and reduces the internal load. Level of Evidence II; Diagnostic studies - Investigation of an examination for diagnosis.

RESUMO Introdução: A suplementação de bicarbonato de sódio (NaHCO3) tem demonstrado atenuar a fadiga e melhorar o desempenho do exercício de alta intensidade, mas os efeitos sobre a manutenção de contrações isométricas são pouco claros. Objetivo: Investigar o efeito do NaHCO3 no desempenho de indivíduos submetidos ao protocolo de fadiga em exercício isométrico no dinamômetro isocinético. Métodos: Doze homens participaram do estudo randomizado, duplo-cego, cruzado e controlado por placebo. Sessenta minutos após ingestão de 0,3 g/kg de massa corporal de NaHCO3 ou placebo, os participantes realizaram protocolo isométrico de fadiga dos extensores do joelho direito, com duração de oito minutos, a 70% da contração isométrica voluntária máxima. Foi considerado indicador de fadiga o momento em que o torque aplicado diminuiu para 50% do valor inicial. A duração da resistência foi avaliada com a manutenção da tarefa acima de 50% do torque inicial. As concentrações de lactato e pH do sangue, assim como os índices de percepção subjetiva de esforço (PSE) e dor (PSD) foram analisados. A PSE da sessão foi avaliada 30 minutos após o teste. Resultados: O pH sanguíneo foi maior pré-protocolo e no indicador de fadiga após ingestão de NaHCO3, assim como as concentrações de lactato sanguíneo no indicador da fadiga e ao final do protocolo (p < 0,001). A suplementação de NaHCO3 aumentou o tempo para atingir a fadiga e atenuou o declínio do pico de torque isométrico no final do protocolo (p < 0,001). A PSE e PSD foram menores ao final do protocolo com NaHCO3 e a PSE da sessão foi atenuada (p < 0,001). Conclusão: A suplementação de NaHCO3 melhora o desempenho de contrações isométricas sustentadas e atenua a carga interna. Nível de Evidência II; Estudos diagnósticos - Investigação de um exame para diagnóstico.

RESUMEN Introducción: La suplementación de bicarbonato de sodio (NaHCO3) ha demostrado atenuar la fatiga y mejorar el desempeño del ejercicio de alta intensidad, pero los efectos sobre el mantenimiento de contracciones isométricas son poco claros. Objetivo: Investigar el efecto de NaHCO3 en el desempeño de individuos sometidos al protocolo de fatiga en ejercicio isométrico en el dinamómetro isocinético. Métodos: Doce hombres participaron del estudio aleatorizado, doble ciego, cruzado y controlado por placebo. Sesenta minutos después de la ingestión de 0,3 g/kg de masa corporal de NaHCO3 o placebo, los participantes realizaron protocolo isométrico de fatiga de los extensores de la rodilla derecha con duración de ocho minutos a 70% de la contracción isométrica voluntaria máxima. Se consideró indicador de fatiga el momento en que el torque aplicado disminuyó para 50% del valor inicial. La duración de la resistencia fue evaluada con el mantenimiento de la tarea por encima del 50% del torque inicial. Fueron analizadas las concentraciones de lactato y pH sanguíneos, así como los índices de percepción subjetiva de esfuerzo (PSE) y dolor (PSD). La PSE de la sesión fue evaluada 30 minutos después del test. Resultados: El pH sanguíneo fue mayor pre-protocolo y en el indicador de fatiga después de la ingestión de NaHCO3, así como las concentraciones de lactato sanguíneo en el indicador de la fatiga y al final del protocolo (p<0,001). La suplementación de NaHCO3 aumentó el tiempo para alcanzar la fatiga y atenuó el declive del pico de torque isométrico al final del protocolo (p<0,001). La PSE y PSD fueron menores al final del protocolo con NaHCO3 y la PSE de la sesión fue atenuada (p<0,001). Conclusión: La suplementación de NaHCO3 mejora el rendimiento de las contracciones isométricas sostenidas y atenúa la carga interna. Nivel de Evidencia II; Estudios diagnósticos - Investigación de un examen para diagnóstico.

A case of Gitelman syndrome: our experience with a patient treated in clinical practice on a local island / Journal of Rural Medicine

Background: Gitelman syndrome (GS) is an autosomal recessive salt-losing renal tubulopathy resulting from mutations in the thiazide-sensitive Na-Cl cotransporter (NCC) gene. Notably, lack of awareness regarding GS and difficulty with prompt diagnosis are observed in clinical practice, particularly in rural settings.Case presentation: We report a case of a 48-year-old man with GS who presented to a local clinic on a remote island. Occasional laboratory investigations incidentally revealed a reduced serum potassium level of 2.6 mmol/L. A careful medical interview revealed episodes of intermittent paralysis of the lower extremities and muscular weakness for >30 years. Subsequent laboratory investigations revealed hypomagnesemia, hypocalciuria, and hypokalemic metabolic alkalosis. Based on the patient’s history, clinical presentation, and laboratory investigations, we suspected GS. Genetic testing revealed a rare homozygous in-frame 18 base insertion in the NCC gene that might have resulted from the founder effect, consequent to his topographically isolated circumstances.Conclusion: More case studies similar to our study need to be added to the literature to gain a deeper understanding of the functional consequences of this mutation and to establish optimal management strategies for this condition, particularly in rural clinical settings.

Síndrome pseudo Bartter asociado a la infusión endovenosa de colistina

RESUMEN El Síndrome Pseudo Bartter (PB) es una patología rara que consiste en una tubulopatía perdedora de sal debida a una alteración en la función de la rama ascendente del asa de Henle. Puede estar asociada con el uso de fármacos como la colistina. Conduce a una disminución sérica de electrolitos en sangre con hiperreninemia, hiperaldosteronemia y alcalosis metabólica, con repercusión en el área neuromotora y cardiovascular principalmente. Presentamos una serie de 3 pacientes que recibieron tratamiento con colistina, con edad media 66,6±20,4 años, predomino del sexo femenino. El Síndrome PB apareció a los 13,6±4,7 días del uso de colistina. Tras la instauración terapéutica presentaron disminución sérica de calcio, potasio y magnesio, acompañados de alcalosis metabólica y normotensión, resolviendo el cuadro a los 5,6±3,2 días. La aparición del Síndrome PB tras el uso de la colistina es rara, las alteraciones producidas por la tubulopatía no responden a la corrección insistente de los déficits solamente, requieren de tratamiento adicional para su resolución. La falta de conocimiento de esta complicación puede presentar desenlaces fatales para los pacientes y una intervención oportuna produce soluciones aparentemente alentadoras.

ABSTRACT Pseudo Bartter Syndrome (PB) is a rare pathology that consists of a salt-losing tubulopathy due to an alteration in the function of the ascending limp of the loop of Henle. It may be associated with the use of drugs such as colistin. It leads to a serum decrease of blood electrolytes with hyperreninism, hyperaldosteronism and metabolic alkalosis, with repercussion in the neuromotor and cardiovascular areas mainly. We present a series of 3 patients who received treatment with colistin, with a mean age of 66,6±20,4 years, predominantly female. PB Syndrome appeared at 13,6±4,7 days after the use of colistin. After the therapeutic initiation they presented serum decrease of calcium, potassium and magnesium, accompanied by metabolic alkalosis and normal blood pressure, all of them have shown resolution of the metabolic disturbances at 5,6±3,2 days. The appearance of PB Syndrome after the use of colistin is rare. The alterations produced by the tubulopathy do not respond to the insistent correction of the deficits only and require additional treatment for their resolution. The lack of knowledge of this complication could lead to fatal outcomes for patients and a timely intervention produces apparently encouraging solutions.

Situación del estado ácido-base de pacientes incidentes a la emergencia de Medicina de un hospital nacional de Lima Perú y su asociación a variables clínicas / Situation of the acid-base disorders and their association with clinical variables in incident patients at the emergency room in a national hospital in Lima, Peru

Objetivos: Determinar la frecuencia de trastornos del estado ácido-base de pacientes admitidos al Departamento de Emergencia de un hospital general de Lima-Perú y su asociación con enfermedades prevalentes. Material y métodos: Estudio transversal descriptivo y analítico cuyo tamaño de muestra calculado fue en 108 pacientes a quienes el médico tratante solicitó estudio de gasometría arterial. La muestra fue obtenida por saturación hasta alcanzar el tamaño mínimo calculado. Resultados: El disturbio ácido-base más frecuentemente hallado fue el trastorno mixto de la acidosis metabólica asociado con la alcalosis respiratoria (50% casos) coexistiendo en pacientes con disfunción renal aguda o crónica y shock, seguido del disturbio único de alcalosis respiratoria (26,2% casos) asociada a enfermedad respiratoria y gastrointestinal. Conclusiones: Los trastornos mixtos de acidosis metabólica con alcalosis respiratoria son altamente relevantes y la alcalosis respiratoria es el fenómeno puro más frecuente. (AU)

Objectives: To determine the frequency of acid-base disorders and their association with prevalent diseases in patients admitted to the emergency department of a national hospital in Lima. Methods: Cross-sectional study with a sample size of 108 patients in whom the treating physician requested arterial blood gases determination. The sample was attained by saturation until reaching the targeted sample size. Results: The most common acid-base disorder was mixed metabolic acidosis (50%) co-existing in patients with acute or chronic renal dysfunction and shock, followed by respiratory alkalosis (26.2%) associated to respiratory and gastro-intestinal disorders. Conclusions: Mixed metabolic acidosis and respiratory alkalosis are the most frequent acid-base abnormalities observed in this setting, respiratory alkalosis is the most common single acid-base disorder found. (AU)

Clinical characterization and diagnosis of cystic fibrosis through exome sequencing in Chinese infants with Bartter-syndrome-like hypokalemia alkalosis / 医学前沿

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.

Síndrome de pseudo-Bartter como presentación inicial de fibrosis quística

Las manifestaciones clínicas de la fibrosis quística comprometen diferentes órganos; siendo los sistemas respiratorio y gastrointestinal los más frecuentemente afectados. Puede presentarse como un desequilibrio ácido-base y electrolítico conocido como síndrome de pseudo-Bartter que se define como un episodio de deshidratación con alcalosis metabólica hipoclorémica hiponatrémica e hipocalémica en ausencia de alteración tubular renal. Se presenta el caso clínico de un lactante menor masculino de cuatro meses con dos hospitalizaciones previas por deshidratación moderada y desequilibrio hidroelectrolítico con hiponatremia. La tercera hospitalización fue el 27 de enero de 2017 por 20 días. En esta ocasión fue admitido por gastroenteritis aguda, con deshidratación moderada, desequilibrio hidroelectrolítico, y observación por un trastorno metabólico. Por presentar deshidratación con alcalosis metabólica hipoclorémica hiponatrémica e hipocalémica sin tubulopatía renal se diagnosticó síndrome de pseudo Bartter y se sospechó fibrosis quística que se corroboró con medición de electrolitos en sudor y análisis molecular de las mutaciones . Conclusión: Debe considerarse el diagnóstico de fibrosis quística en un niño, sobre todo menor de dos años, con deshidratación, alcalosis metabólica hiponatrémica hipoclorémica aunque no haya presentado síntomas respiratorios o gastrointestinales típicos de la enfermedad. El diagnóstico temprano es fundamental para mejorar el pronóstico y la sobrevida a largo plazo

The clinical manifestations of cystic fibrosis may involve multiple organs. Although the respiratory and gastrointestinal are the most commonly affected systems, it can present as an acid- base and electrolyte imbalance called pseudo -Bartter syndrome which is defined as an episode of dehidration with metbolic alkalosis with hypochloremia, hyponatremia and hypokalemia in the absence of renal tubular pathology. We report a case of a 4-month-old male infant with 2 previous episodes of moderate dehydration and hydroelectrolyte imbalance with hyponatremia. He was admitted on January 27 th 2017 for 20-days hospital stay. On his 3th hospitalization, he was admitted with acute gastroenteritis, moderate dehydration, hydroelectrolyte imbalance, and probable metabolic disorder. Due to the presence of metabolic hypochloremic alkalosis with hyponatremia and hypokalemia without renal tubulopathy, Pseudo Bartter Syndrome was diagnosed and cystic fibrosis was suspected and corroborated later with the measurement of sweat electrolytes and molecular analysis of mutations. Conclusion: The diagnosis of cystic fibrosis must be suspected in a child, especially those under 2 years old, with hyponatremic hypochloremic,hypokalemic metabolic alkalosis dehydration should be considered even in the absence of respiratory or gastrointestinal symptoms, which are typically present in this disease. An early diagnosis is essential to improve the prognosis and long term survivor

Aproximación físico-química a las alteraciones ácido base en la orina de ovinos con alcalosis hipoclorémica / Physical-chemical approach to acid-base alterations in the urine of sheep with hypochloremic alkalosis / Aproximação físico-química às alterações ácido base na urina de ovinos com alcalose hipoclórica

Resumen La aproximación físico-química para determinar el pH urinario es relativamente nueva y no se ha usado en condiciones patológicas en animales. En el presente artículo, el objetivo principal fue demostrar la validez de esta teoría en la orina de ovinos con alcalosis metabólica hipoclorémica. Se realizó un estudio de tipo experimental para la inducción de la alcalosis metabólica hipoclorémica en ovinos. Durante el periodo de control y de inducción se determinaron en la orina: pH calculado, pH medido, excreción neta de ácido, amonio y diferencia de iones fuertes en la orina (SID) cada 24 h hasta el desarrollo de la aciduria paradójica o el deterioro físico de los sujetos. Se determinó la correlación de Pearson (p) entre el pH medido y calculado a partir del modelo del SID en la orina. Se observó una correlación alta entre el pH urinario medido y el calculado usando el SID calculado con base en la excreción neta de ácido (p = 0,874). La correlación entre SID calculado y pH en orina fue significativa (p = 0,839). Sin embargo, la correlación entre el SID y el pH medido de la orina fue moderada (p = 0,588). Se concluye que existe una alta correlación entre el pH calculado a partir del SID usando la excreción neta de ácido y el pH medido en la orina de ovinos con alcalosis metabólica hipoclorémica. Esto indica que el pH urinario depende fuertemente del SID y, por lo tanto, la reducción en el pH puede ser explicada por la disminución del SID.

Abstract The physical-chemical approach to determine urinary pH is relatively new and has not yet been used in pathological conditions in animals. The main objective of this paper was to demonstrate the validity of this theory in the urine of sheep with hypochloremic metabolic alkalosis. An experimental-type study was conducted to induce hypochloremic metabolic alkalosis in sheep. During the control and induction periods, calculated pH, measured pH, net acid excretion, ammonium and strong ion difference (SID) in urine were examined every 24 hours until development of paradoxical aciduria or physical deterioration of subjects. Pearson's correlation (p) was determined between measured and calculated pH based on SID in urine. A high correlation between measured and calculated urine pH was observed using SID calculated from net acid excretion (p = 0.874). The correlation between calculated SID and urine pH was significant (p = 0.839). However, the correlation between SID and measured urine pH was moderate (p = 0.588). It is concluded that there is a high correlation between pH calculated from SID using net acid excretion and pH measured in the urine of sheep with hypochloremic metabolic alkalosis. This indicates that urine pH depends strongly on SID and, therefore, a reduction in pH can be explained by a decrease in SID.

Resumo A aproximação físico-química para determinar o pH urinário é relativamente nova e não tem sido usado em condições patológicas em animais. Neste artigo, o objetivo principal foi demonstrar a validez desta teoria na urina de ovinos com alcalose metabólica hipoclórica. Realizou-se um estudo de tipo experimental para a indução da alcalose metabólica hipoclórica em ovinos. Durante o período de controle e de indução determinaram na urina: pH calculado, pH medido, excreção neta de ácido, amônio e diferença de íons fortes na urina (SID) cada 24 horas hasta o desenvolvimento da aciduria paradoxal ou a deterioração física dos sujeitos. Determinou-se a correlação de Pearson (p) entre o pH medido e calculado a partir do modelo do SID na urina. Observou-se uma correlação alta entre o pH urinário medido e o calculado usando o SID calculado a partir da ex creção líquida de ácido (p = 0,874). A correlação entre SID calculado e pH em urina foi significativa (p = 0,839). Contudo, a correlação entre o SID e o pH medido da urina foi moderada (p = 0.588). Conclui-se que existe uma alta correlação entre o pH calculado a partir do SID usando a excreção líquida de ácido e o pH medido na urina de ovinos com alcalose metabólica hipoclórica. Isto indica que o pH urinário depende fortemente do SID e, portanto, a redução no pH pode ser explicada pela diminuição do SID.

Alcalose metabólica induzida por bicarbonato de sódio: mecanismos de ação, dose utilizada e efeitos sobre o desempenho em ciclismo de alta intensidade / Induced metabolic alkalosis by sodium bicarbonate: action mechanisms, dose and effects on highintensity cycling performance

A relação entre a alcalose metabólica e o desempenho esportivo tem sido investigada através de anipulações do pH sanguíneo. Entre as formas de manipulação do pH, o bicarbonato de sódio (NaHCO3) é o componente químico mais utilizado quando se pretende induzir um estado de alcalose sanguínea previamente ao exercício. Embora os benefícios do NaHCO3 no desempenho tenham sido amplamente demonstrados em exercícios intermitentes de alta intensidade, não há um consenso na literatura e pouco ainda é conhecido quanto aos efeitos do NaHCO3 em exercícios contínuos de ciclismo de alta intensidade. Nesse sentido, foram abordados na presente revisão os principais aspectos envolvidos na ingestão aguda e crônica de NaHCO3, enfatizando os mecanismos de ação dessa substância, especificações acerca da dose utilizada e seus efeitos sobre o desempenho em ciclismo de alta intensidade. Os resultados dos estudos apresentados na presente revisão revelam que a ingestão aguda de 0,3 g∙kg-1 de massa corporal (MC) de NaHCO3 é eficaz em melhorar o desempenho em eventos de alta intensidade se consumido em torno de 90 minutos antes do exercício. Para a ingestão crônica, uma dose de 0,5 g∙kg-1 ∙dia1 de MC durante 5-6 dias seria benéfica para o exercício de alta intensidade. Esses seriam os limites em ambos os protocolos para induzir um estado de alcalose metabólica e posteriormente melhorar o desempenho sem promover ou atenuando qualquer sintoma relacionado à sensações de desconforto gastrointestinal. Dessa forma, ambas as formas de ingestão de NaHCO3, aguda e/ou crônica, parecem melhorar o desempenho durante o ciclismo de alta intensidade realizados de modo contínuo, enfatizando a importância da suplementação de NaHCO3 como um recurso ergogênico. Porém, pesquisas adicionais utilizando protocolos de ingestão crônica e testando seus efeitos sobre o desempenho em provas mais prolongadas são requeridas devido ao reduzido número de investigações e o potencial efeito ergogênico dessa substância...(AU)

The relationship between metabolic alkalosis and exercise performance has been investigated through manipulation of the blood and muscle pH. Among the forms of pH manipulation, the sodium bicarbonate (NaHCO3) is the most used chemical component when is intentioned to induce a blood alkalosis state prior to exercise. While the benefits of NaHCO3 in performance have been widely demonstrated in high-intensity intermittent exercise, there is no consensus in the literature and little is known about the effects of NaHCO3 in continuous high-intensity cycling exercise. Thus, it was addressed in this present review the main aspects involved in acute and chronic NaHCO3 ingestion, giving a focus to the action mechanisms of this substance, specifications about the used dose and their effects on highintensity cycling performance. The results of the present review show that acute ingestion of 0.3 g∙kg-1 of body mass (BM) of NaHCO3 is effective in improving performance in high-intensity events if this substance is consumed in about 90 minutes prior to exercise. For chronic ingestion, a dose of 0.5 g∙kg1 ∙day-1 BM during 5-6 days should be beneficial for the high-intensity exercise. For both protocols these would be the limits to induce a metabolic alkalosis state and further improve the performance without promoting or attenuating any symptoms related to the gastrointestinal discomfort sensations. Thus, both acute and/or chronic NaHCO3 ingestion seem to improve performance during high-intensity cycling performed in a continuous mode, emphasizing the importance of NaHCO3 supplementation as an ergogenic aid. However, further research using chronic ingestion of protocols and testing their effects on performance in more prolonged tests are required due to the small number of studies and the potential ergogenic effect of this substance...(AU)

Síndrome de pseudo-Bartter en paciente pediátrico con fibrosis quí­stica estable / Pseudo-Bartter syndrome in stable cystic fibrosis pediatric patient

The pseudo-Bartter´s syndrome (PBS) is a disorder characterized by metabolic alkalosis, hyponatremia, hypochloremia, hypokalemia in the absence of renal tubular disease. The PBS can be one of the complications of cystic fibrosis or may be the initial presentation of the disease in children and adults. The objective is to present a clinical case emphasysing the importance of diagnostic suspicion in cystic fibrosis.

El síndrome de Pseudo-Bartter (SPB) se caracteriza por alcalosis metabólica, hiponatremia, hipocloremia, hipocalemia en ausencia de enfermedad tubular renal. El SPB puede ser una complicación de la Fibrosis Quística (FQ) o la forma de presentación inicial de esta enfermedad, en niños y en adultos. El objetivo es presentar un caso clínico, enfatizando en la importancia de tener un alto índice de sospecha de esta condición.