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2.
Am J Physiol Renal Physiol ; 318(6): F1418-F1429, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32308019

RESUMO

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of ß-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. In study 1 (n = 10), patients became alkalemic using 37 meq/L dialysate bicarbonate; in contrast, with the use of 27 meq/L dialysate, net bicarbonate loss occurred and blood bicarbonate decreased. Total OA losses were not higher with 37 meq/L dialysate bicarbonate (50.9 vs. 49.1 meq using 27 meq/L, P = 0.66); serum BHB increased in both treatments similarly (P = 0.27); and blood lactate was only slightly higher with the use of 37 meq/L dialysate (P = 0.048), differing by 0.2 meq/L at the end of hemodialysis. In study 2 (n = 7), patients achieved steady state on two bicarbonate prescriptions: they were significantly more acidemic when dialyzed against a 30 meq/L bicarbonate dialysate compared with 35 meq/L and, as in study 1, became alkalemic when dialyzed against the higher bicarbonate dialysate. OA losses were similar to those in study 1 and again did not differ between treatments (38.9 vs. 43.5 meq, P = 0.42). Finally, free fatty acid levels increased throughout hemodialysis and correlated with the change in serum BHB (r = 0.81, P < 0.001), implicating upregulation of lipolysis as the mechanism for increased ketone production. In conclusion, lowering dialysate bicarbonate does not meaningfully reduce organic acid generation during hemodialysis or modify organic anion losses into dialysate.


Assuntos
Ácido 3-Hidroxibutírico/sangue , Equilíbrio Ácido-Base , Alcalose/sangue , Bicarbonatos/administração & dosagem , Soluções para Hemodiálise/administração & dosagem , Falência Renal Crônica/terapia , Ácido Láctico/sangue , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcalose/diagnóstico , Alcalose/etiologia , Alcalose/fisiopatologia , Bicarbonatos/efeitos adversos , Bicarbonatos/metabolismo , Biomarcadores/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Soluções para Hemodiálise/efeitos adversos , Soluções para Hemodiálise/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Lipólise , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
Eur J Med Genet ; 62(10): 103728, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31325522

RESUMO

Persistent hypokalemic hypochloremic metabolic alkalosis represents a heterogeneous group of genetic disorders of which the most common is Bartter syndrome (BS). BS is an inherited renal tubulopathy caused by defective salt reabsorption in the thick ascending loop of Henle, which results in persistent hypokalemic hypochloremic metabolic alkalosis. Here we report a 10-year-old girl of a consanguineous family. She presented prenatally with severe polyhydramnios and distended bowel loops. Thereafter, she displayed failure to thrive and had recurrent admissions due to dehydration episodes associated with diarrhea, and characterized by hypokalemia, hypochloremia and metabolic alkalosis. BS was considered her working diagnosis for several years despite negative genetic analysis of the known genes associated with BS. Whole exome sequencing identified a novel homozygous c.1652delT deleterious frameshift mutation in the SLC26A3 gene, which confirmed the diagnosis of congenital chloride diarrhea (CCD), a rare autosomal recessive disease that mimics biochemically BS. A review of twelve additional reported cases of CCD that were initially misdiagnosed as BS, emphasizes CCD in the differential diagnosis of BS, and highlights the clinical discrepancies between these two entities. Taken together, our report further emphasizes the typical clinical features of CCD, and the importance of next generation sequencing in the diagnosis of syndromes with genetic heterogeneity. We suggest including SLC26A3 in the extended BS targeted gene panels.


Assuntos
Alcalose/diagnóstico , Alcalose/genética , Sequenciamento de Nucleotídeos em Larga Escala , Hipopotassemia/sangue , Hipopotassemia/diagnóstico , Alcalose/sangue , Criança , Diagnóstico Diferencial , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Testes Genéticos , Humanos
7.
Acta Clin Belg ; 74(1): 34-40, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30369299

RESUMO

Metabolic alkalosis defined by the increase of both plasma HCO3- level (>26 mmol/L) and blood arterial pH (>7.43) is quite frequent and usually accompanied by hypokalemia. Its pathogenesis requires both the generation of alkalosis and its maintenance. Generation may be due to excessive hydrogen ion loss by the gastrointestinal tract (e.g. vomiting) or by the kidney (e.g. use of loop diuretics) or may be due to exogenous base gain. Maintenance reflects the inability of the kidney to excrete the excess of bicarbonate because of hypovolemia, chloride depletion, hypokalemia, hyperaldosteronism, renal failure or a combination of these factors. The evaluation of volemic status and measurement of urinary Cl- and plasma levels of renin and aldosterone are crucial to identify the cause(s) of metabolic alkalosis. The cornerstone of treatment is the correction of existing depletions and the prevention of further losses. In vomiting-induced chloride depletion alkalosis, infusion of potassium chloride restores the excretion of bicarbonate by the kidney.


Assuntos
Alcalose/etiologia , Idoso de 80 Anos ou mais , Alcalose/diagnóstico , Alcalose/terapia , Diagnóstico Diferencial , Feminino , Humanos
8.
Nephrol Dial Transplant ; 34(1): 38-39, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29982819

RESUMO

Hypokalaemia with alkalosis can suggest excess aldosterone. Aldosterone stimulates the collecting duct mineralocorticoid receptor (MR) to upregulate the epithelial sodium channel (ENaC) and stimulate electrogenic sodium reabsorption, with secretion of potassium and protons. Gitelman, Bartter and Liddle syndrome, and liquorice ingestion all cause hypokalaemic alkalosis. This mini-review outlines the pathophysiology of these conditions as well as how to differentiate them.


Assuntos
Alcalose/diagnóstico , Síndrome de Bartter/diagnóstico , Biomarcadores/metabolismo , Glycyrrhiza/efeitos adversos , Hipopotassemia/diagnóstico , Aldosterona/metabolismo , Alcalose/etiologia , Alcalose/metabolismo , Síndrome de Bartter/complicações , Síndrome de Bartter/metabolismo , Diagnóstico Diferencial , Canais Epiteliais de Sódio/metabolismo , Humanos , Hipopotassemia/etiologia , Hipopotassemia/metabolismo , Túbulos Renais/metabolismo , Potássio/metabolismo , Sódio/metabolismo
9.
Nephron ; 139(4): 293-298, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29649820

RESUMO

BACKGROUND: Acid-base disturbances are frequent in critically ill patients. Arterial blood gas (ABG) is the gold standard in the diagnosis of these disturbances, but it is invasive with potential hazards. For patients with a central venous catheter, venous blood gas (VBG) sampling may be an alternative, less-invasive diagnostic tool. However, the accuracy of a central VBG-based acid-base disorder diagnosis compared to an ABG is unknown. The primary objective of this study was to assess the accuracy of a central VBG-based acid-base disorder diagnosis compared to the "gold standard" ABG in critically ill patients. METHODS: This was a study of adult patients in a medical intensive care unit that had simultaneously drawn ABG and central VBG samples. Expert acid-base diagnosticians, all nephrologists, diagnosed the acid-base disorder(s) in each blood gas sample. The central VBG diagnostic accuracy was assessed with percent agreement, sensitivity, and specificity compared to the ABG-based diagnosis. RESULTS: The study involved 23 participants. Overall, the central VBG had 100% sensitivity for metabolic acidosis, metabolic alkalosis, and respiratory acidosis, and lower sensitivity (71%) for respiratory alkalosis, and high percent agreement, ranging from 75 to 94%. VBG-based diagnoses in vasopressor-dependent patients (n = 13, 56.5%) performed similarly to the entire sample. CONCLUSIONS: In critically ill adult patients, central VBG may be used to detect and diagnose acid-base disturbances with reasonable diagnostic accuracy, even in shock states, compared to the ABG. This study supports the use of central VBG for diagnosis of acid-base disturbances in critically ill patients.


Assuntos
Equilíbrio Ácido-Base , Desequilíbrio Ácido-Base/diagnóstico , Gasometria/métodos , Cuidados Críticos/métodos , Desequilíbrio Ácido-Base/sangue , Acidose/diagnóstico , Adulto , Idoso , Alcalose/diagnóstico , Cateterismo Venoso Central , Estado Terminal , Estudos Transversais , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
BMJ Case Rep ; 20182018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29535093

RESUMO

A 62-year-old woman presented with an 11-month history of worsening nasal symptoms of rhinorrhoea, anosmia, nasal congestion and intermittent epistaxis. MRI revealed a large mass in the upper nasal vault. Biopsy of the mass revealed an olfactory neuroblastoma. While waiting resection, she acutely developed severe proximal muscle weakness, lethargy and lower extremity oedema. Blood glucose was elevated, and hypokalaemic metabolic alkalosis was noted. Elevated serum cortisol level of 95.7 µg/dL (8.7-22.4 µg/dL) and markedly elevated 24-hour urinary cortisol level of 6962.3 µg/24 hours (4.0-50.0 µg/24 hours) with concurrent adrenocorticotropic hormone (ACTH) level of 171 pg/mL (6-58 pg/mL) were suggestive of an ACTH-dependent source of hypercortisolism. A subsequent positive high-dose dexamethasone suppression test was consistent with ectopic ACTH production. She underwent near-total resection of the right nasal mass followed by radiotherapy, resulting in complete resolution of signs and symptoms of cortisol excess.


Assuntos
Síndrome de ACTH Ectópico/terapia , Alcalose/diagnóstico , Estesioneuroblastoma Olfatório/diagnóstico por imagem , Hipopotassemia/diagnóstico , Imagem por Ressonância Magnética , Cavidade Nasal/diagnóstico por imagem , Neoplasias Nasais/diagnóstico por imagem , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/diagnóstico , Alcalose/terapia , Estesioneuroblastoma Olfatório/cirurgia , Feminino , Humanos , Hidrocortisona/uso terapêutico , Hipopotassemia/terapia , Pessoa de Meia-Idade , Cavidade Nasal/patologia , Neoplasias Nasais/cirurgia , Resultado do Tratamento
16.
Vet Clin North Am Small Anim Pract ; 47(2): 197-200, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27914757

RESUMO

Metabolic alkalemia is characterized by an increase in bicarbonate concentration and base excess, an increase in pH, and a compensatory increase in carbon dioxide pressure. This article outlines indications for analysis, reference ranges, causes, and clinical signs of metabolic alkalosis. Algorithms for evaluation of patients with acid-base disorders and metabolic alkalosis are included.


Assuntos
Alcalose/veterinária , Doenças do Gato/etiologia , Doenças do Cão/etiologia , Desequilíbrio Ácido-Base , Alcalose/diagnóstico , Alcalose/etiologia , Animais , Bicarbonatos/metabolismo , Doenças do Gato/diagnóstico , Gatos , Doenças do Cão/diagnóstico , Cães
20.
J Clin Endocrinol Metab ; 101(6): 2390-5, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27050945

RESUMO

CONTEXT AND OBJECTIVE: Diabetic ketoacidosis (DKA) is associated with a metabolic alkalosis, which is thought to be due to vomiting. However, alkalosis can occur in DKA without vomiting. We retrospectively reviewed the acid-base disturbances in DKA admissions without vomiting. PARTICIPANTS AND METHODS: We included admissions of the patients with blood glucose and beta-hydroxybutyrate (ßOHB) levels > 250 mg/dL and > 1.0 mmol/L, respectively. Admissions without vomiting were classified into a group with a ßOHB > 3.0 mmol/L (DKA group) and a group with ßOHB of 1.0-3.0 mmol/L (pre-DKA group). The acid-base status was analyzed by the modified base excess (BE) method. BE effects were calculated by changes in sodium (BE free water, [BEFW]), and chloride (BECl). Positive and negative values for each parameter suggested alkalosis and acidosis, respectively. RESULTS: Forty-five included admissions were divided into DKA (n = 34) and pre-DKA (n =11) groups. Sodium-corrected chloride level and the chloride/sodium ratio were significantly lower in the DKA group than in the pre-DKA group. In both groups, BEFW values were modestly negative. The mean BECl values were positive in both groups, but significantly higher in the DKA group. The alkalinizing effects by hypochloremia diminished the base deficit in the DKA group by approximately 25%. The BECl value significantly correlated with serum total ketone levels (r = 0.66; P < .0001). CONCLUSION: The modified BE method successfully proved the presence of hypochloremic alkalosis in DKA without vomiting. This suggests the direct participation of serum ketoacids in the pathogenesis of hypochloremic alkalosis.


Assuntos
Alcalose/diagnóstico , Cetoacidose Diabética/sangue , Adulto , Idoso , Alcalose/sangue , Alcalose/complicações , Glicemia , Cetoacidose Diabética/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Desequilíbrio Hidroeletrolítico , Adulto Jovem
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