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Potassium is an unusual fixed Post Date: Thu, 16 Oct 2008 20:04:55 +0000 This, in turn, is an important determinant of both the availability of hydrogen ion for secretion and the disposition of the hydrogen ion within the tubular fluid.Potassium Reabsorption and Secretion. Potassium is an unusual fixed cation in that it undergoes both tubular reabsorption and secretion. Autor of the post: Undefined As judged by the action Post Date: Thu, 16 Oct 2008 19:53:07 +0000 Reabsorption occurs largely in the proximal tubule, secretion in the distal tubule (3 in Figure VIII-1). Since the major fraction of the filtered potassium is reabsorbed, and since this process is relatively immune to physiological stimuli or pharmacological agents, it follows, therefore, that variations in the amount of potassium actually excreted may be attributed to the distal secretory mechanism. As judged by the action of many diuretic agents, the volume of unreabsorbed glomerular filtrate that flows through the distal tubule is one of the determinants of the rate of potassium secretion. Autor of the post: Undefined Potentially bidirectional transport provides separate mechanisms Post Date: Thu, 16 Oct 2008 19:38:48 +0000 Thus, some drugs have the dual effect of increasing the urinary excretion of both sodium and potassium, the former by inhibition of reabsorption and the latter by augmentation of secretion (3 in Figure VIII-1). Scheme for renal transport of exogenous organic acids and bases.Potentially bidirectional transport provides separate mechanisms by which rate of excretion may be altered pharmacologically. Autor of the post: Undefined Two major secretory mechanisms for Post Date: Thu, 16 Oct 2008 19:23:04 +0000 Many drugs and drug metabolites are handled by these mechanisms.Excretion of Organic Acids and Bases. Two major secretory mechanisms for elimination of foreign organic compounds may now be identified in the proximal tubule: one for the transport of organic acids, the other for organic bases (see Figure VIII-3). Autor of the post: Undefined This is a consequence Post Date: Thu, 16 Oct 2008 19:03:46 +0000 While both mechanisms are dependent on energy derived from cellular metabolism, they are essentially independent systems, particularly to the extent that substances that compete for transport in one system do not influence the other. It has also been shown that some compounds that undergo tubular secretion may not necessarily be excreted in large amounts in the voided urine. This is a consequence of tubular reabsorption. Autor of the post: Undefined Since this appears Post Date: Thu, 16 Oct 2008 18:45:33 +0000 While secretion is an active mechanism, reabsorption of most of these compounds is passive and depends primarily on the permeability of the tubular epithelium to the nonionic moiety of the specific acid or base under consideration. The degree of reabsorption is correlated with the lipid solubility of the nonionic species. Since this appears to be a diffusion process, the magnitude of reabsorption depends on the concentration gradient of the nonionic form from tubular fluid to the peritubular space, and this, in turn, is influenced by the pH and volume of tubular fluid and by the pKa of the compound in question (see Chapter 1). Autor of the post: Undefined This complex system provides two separate Post Date: Thu, 16 Oct 2008 18:26:49 +0000 As a consequence, urine flow and urine pH are important factors in determining the rate of excretion for salicylate, probenecid, other benzoates, and many tertiary amines, all of which also undergo active tubular secretion. However, these same physiological variables, urine flow and pH, have relatively little influence on the excretion of hippurates or other lipid-insoluble compounds to which the renal tubular epithelium is impermeable.This complex system provides two separate means by which therapeutic agents may influence the excretion rate of an organic acid or base. Autor of the post: Undefined Diuretics are agents that increase Post Date: Thu, 16 Oct 2008 18:13:27 +0000 First, carrier-mediated transport mechanisms may be influenced by specific compounds. Second, the extent of ionization of weak acids or bases will be influenced by acidifying or alkalinizing agents; this and the rate of urine flow, which may be directly or indirectly influenced by drugs, will alter the amounts of such compounds that are reabsorbed by diffusion.Diuretics are agents that increase the rate of urine formation. Autor of the post: Undefined Under some conditions, the maintenance Post Date: Thu, 16 Oct 2008 17:53:47 +0000 Despite this simple definition, a large number of physiological and pharmacological factors are involved. It should also be emphasized that by common usage the term diuresis has two separate connotations: one refers to the increase in urine volume per se, the other to the net loss of solute and water. Under some conditions, the maintenance of an adequate urine volume in itself justifies the use of diuretic agents. Autor of the post: Undefined In general, the different types Post Date: Thu, 16 Oct 2008 17:38:00 +0000 However, by far the most important indication is the mobilization of edema fluid, that is, the production of a negative extracellularfluid balance. The effects of diuretics on solute excretion are of major importance for the understanding both of the underlying mechanisms of drug action and of the conse-quences of therapy. In general, the different types of diuretics are classified according to the manner by which they alter solute excretion. 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