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The concept of free-water production Post Date: Fri, 17 Oct 2008 1:22:40 +0000 While it is true that free-water production must ultimately influence the solute concentration of the residual body fluids, nevertheless, in the clinical use of diuretics the free-water production has relatively minor therapeutic implications. This is partly due to the fact that urinary excretion is promptly balanced by a variable dietary intake of both solute and water.The concept of free-water production has played an interesting role in localizing the site of diuretic action within the nephron. Autor of the post: Undefined There is no evidence Post Date: Fri, 17 Oct 2008 1:12:30 +0000 It must be strongly emphasized that, in order to infer intrarenal sites of action on the basis of the excretion of solute and water, observations must be made under one or the other of two physiological extremes—either in the absence of ADH or under its maximal influence. The former condition is obtained during unequivocal water diuresis or in patients with diabetes insipidus of posterior pituitary origin; the latter conditionmay be achieved by water restriction, infusion of hypertonic solute, or administration of exogenous ADH. There is no evidence that the available diuretic drugs directly alter the action of ADH itself. Autor of the post: Undefined If sodium reabsorption is inhibited Post Date: Fri, 17 Oct 2008 0:57:28 +0000 Figure VIII-2 shows the pattern obtained with three different diuretics. These can be evaluated in terms of the mechanisms and with the nomenclature previously described in Figure VIII-1, The interpretations that have been advanced are essentially as follows. If sodium reabsorption is inhibited in the proximal tubule (ie, 1-A), an increased amount of solute will be delivered to the more distal segments, including the ascending limb (1 -B). Autor of the post: Undefined In addition, in the case Post Date: Fri, 17 Oct 2008 0:40:40 +0000 With the greater load to this latter site, an increased amount of sodium would be reabsorbed along with chloride, leading to an increase in either the positive or the negative free-water production. This is the result obtained with mannitol. In addition, in the case of positive free-water production, some of the increase might also be attributed to augmented sodium reabsorption in the most distal nephron (1-C). Autor of the post: Undefined Despite the resultant diuresis Post Date: Fri, 17 Oct 2008 0:23:20 +0000 A second pattern is illustrated by ethacrynic acid. If chloride and sodium reabsorption were to be inhibited predominantly in the ascending limb (1-B), the urine would tend to remain isosmotic. Despite the resultant diuresis, the production of both positive and negative free water would be impaired. Autor of the post: Undefined Since the rate of negative Post Date: Fri, 17 Oct 2008 0:04:53 +0000 A third possibility is illustrated with chlorothiazide. The findings have been interpreted in terms of the inhibition of sodium reabsorption at a distal site, that is, 1-C. Since the rate of negative free-water production is normal, it is inferred that there is no inhibition of transport in the ascending limb (1-B). Autor of the post: Undefined Of course, the demonstration Post Date: Thu, 16 Oct 2008 23:45:12 +0000 However, since positive free-water production is partially inhibited, it has been proposed that the drug acts at the most distal site of sodium reabsorption.Although there is uncertainty about some of the interpretations that have been proposed, there can be no doubt that different diuretics act by distinct and separate mechanisms as judged by free-water production. Of course, the demonstration of an action at one site does not invariably exclude an action elsewhere. Autor of the post: Undefined In this discussion, the term free-water Post Date: Thu, 16 Oct 2008 23:25:40 +0000 By these criteria, osmotic diuretics and acetazolam-ide act proximally, ethacrynic acid and furosemide act on the ascending limb, and chlorothiazide acts on the distal segment. The site of mercurial action is less conclusive; many studies in the dog appear not to be in agreement with those in man.In this discussion, the term free-water production has been used instead of free-water clearance. Autor of the post: Undefined Despite these semantic difficulties Post Date: Thu, 16 Oct 2008 23:07:05 +0000 In the literature, the term clearance has been employed, with positive free water being designated as CH 0 and negative free water as T° H 0. Despite auspicious precedent, the term Ń˙__0 is incorrect if literally translated as "the renal clearance of water," and the term T° H 0 was initially based on premises that have become obsolete. Despite these semantic difficulties, the concept of free water remains valid, but the term production is preferable to that of clearance. Autor of the post: Undefined The concept of hydrogen ion Post Date: Thu, 16 Oct 2008 22:54:52 +0000 Fine distinctions between actual generation and net production of free water are beyond the scope of the present discussion.Hydrogen Ion Secretion. The concept of hydrogen ion secretion has played an important role in the development of modern theories of renal function and of the action of therapeutic agents. 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