1,721,139 research outputs found
Bartter's and Gitelman's syndromes: Their relationship to the actions of loop and thiazide diuretics
No full textThe wider recognition of inherited Bartter’s and Bartter’s-like
syndromes, especially Gitelman’s, has come largely as
a result of the advances in, and application of, molecular
genetics. By exploiting pre-existing renal cell models
of ion transport, specifically for sodium and potassium, the
known mechanisms and sites of action of loop and thiazide
diuretics and the similarity of their chronic effects to these
syndromes, it was possible for geneticists to take a candidate
gene approach. This was initially successful but, when not all
cases could be explained on this basis, it forced a more
detailed clinical appraisal and better phenotyping, resulting in
the discovery of novel genes involved in controlling renal
sodium, potassium and chloride transport, and new insights
into renal tubular physiology. This is a good example of one
form of ‘translational research’, the message being the
importance of our ability to link (in this instance) basic renal
physiology and pharmacology, with clinical nephrology and
genetics.The wider recognition of inherited Bartter's and Bartter's-like syndromes, especially Gitelman's, has come largely as a result of the advances in, and application of, molecular genetics. By exploiting pre-existing renal cell models of ion transport, specifically for sodium and potassium, the known mechanisms and sites of action of loop and thiazide diuretics and the similarity of their chronic effects to these syndromes, it was possible for geneticists to take a candidate gene approach. This was initially successful but, when not all cases could be explained on this basis, it forced a more detailed clinical appraisal and better phenotyping, resulting in the discovery of novel genes involved in controlling renal sodium, potassium and chloride transport, and new insights into renal tubular physiology. This is a good example of one form of 'translational research', the message being the importance of our ability to link (in this instance) basic renal physiology and pharmacology, with clinical nephrology and genetics. © 2006 Elsevier Ltd. All rights reserved
An overview of divalent cation and citrate handling by the kidney
No full textUrinary calcium, magnesium and citrate levels are important in promoting or inhibiting renal stone formation. Here we review current information on the tubular handling of these ions. Most filtered calcium is reabsorbed in the proximal tubule and the thick ascending limb (TAL) of the loop of Henle, largely paracellularly; most of the remainder is reabsorbed in the distal tubule, transcellularly. Calcium reabsorption in the TAL and distal tubule is stimulated by parathyroid hormone and vitamin D; other factors influencing its renal handling include extracellular volume status and acid-base balance. Little filtered magnesium is reabsorbed in the proximal tubule; the bulk is reabsorbed paracellularly in the TAL, while most of the remainder is reabsorbed transcellularly in the distal tubule. Dietary intake, peptide hormones and chronic potassium depletion can all influence magnesium reabsorption in the TAL and distal tubule. Most filtered citrate is taken up across the apical membrane of the proximal tubule via a sodium-dicarboxylate co-transporter (NaDC-1). It also enters proximal tubular cells across the basolateral membrane; citrate contributes to the cells' oxidative metabolism. Citrate excretion is affected by acidbase balance, acetazolamide treatment, chronic potassium depletion and urinary excretion of calcium and magnesium. Where possible, we have indicated the mechanisms of these complex interactions. Copyright © 2004 S. Karger AG, Basel.Urinary calcium, magnesium and citrate levels are important in promoting or inhibiting renal stone formation. Here we review current information on the tubular handling of these ions. Most filtered calcium is reabsorbed in the proximal tubule and the thick ascending limb (TAL) of the loop of Henle, largely paracellularly; most of the remainder is reabsorbed in the distal tubule, transcellularly. Calcium reabsorption in the TAL and distal tubule is stimulated by parathyroid hormone and vitamin D; other factors influencing its renal handling include extracellular volume status and acid-base balance. Little filtered magnesium is reabsorbed in the proximal tubule; the bulk is reabsorbed paracellularly in the TAL, while most of the remainder is reabsorbed transcellularly in the distal tubule. Dietary intake, peptide hormones and chronic potassium depletion can all influence magnesium reabsorption in the TAL and distal tubule. Most filtered citrate is taken up across the apical membrane of the proximal tubule via a sodium-dicarboxylate co-transporter (NaDC-1). It also enters proximal tubular cells across the basolateral membrane; citrate contributes to the cells' oxidative metabolism. Citrate excretion is affected by acidbase balance, acetazolamide treatment, chronic potassium depletion and urinary excretion of calcium and magnesium. Where possible, we have indicated the mechanisms of these complex interactions. Copyright © 2004 S. Karger AG, Basel
Electrolytes and acid-base: Common fluid and electrolyte disorders
No full textDisturbances of fluid and electrolyte balance are common in clinical practice, especially in a hospital setting, and may be iatrogenic or compounded by inappropriate medical or surgical treatment. Their recognition and appropriate management are not necessarily difficult or complex; while specific formulae and standard protocols can be helpful at the bedside, there is no substitute for an understanding, and application, of some basic principles of renal and endocrine physiology, which is what this article tries to provide. Some knowledge of basic renal physiology (including transport function along the nephron and its regulation) is useful, because it makes it easier to work through, and understand, most clinical disorders of fluid and electrolyte balance. Unfortunately, patients seldom present with a single acid-base or fluid and electrolyte disturbance, so the real challenge is to determine which disorder came first, before rushing in and treating in isolation what might seem to be the major clinical abnormality. First, we need to consider the main homeostatic functions of the kidney and, more specifically, the essential workings of its functional unit, the nephron (glomerulus and renal tubule). © 2011 Elsevier Ltd. All rights reserved
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