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Urate (the base form of uric acid) provides a fascinating example of the renal handling of organic anions that is particularly important for clinical medicine and is illustrative of renal pathology An elevated plasma concentration of urate can cause gout; therefore, its removal from the blood is important However, it is as though the kidney cannot make up its mind what to do with urate Urate is not protein bound and so is freely filterable Almost all the filtered urate is reabsorbed early in the proximal tubule; however, further on in the proximal tubule, urate undergoes active tubular secretion Then, in the straight portion, urate is once again reabsorbed The total rate of tubular reabsorption is normally much greater than the rate of tubular secretion, and so the mass of urate excreted per unit time is only a small fraction of the mass filtered We will not discuss the specific transport steps required to accomplish all of this, but most involve antiporters that exchange urate for another organic anion Although urate reabsorption is greater than secretion, the secretory process is homeostatically controlled to maintain relative constancy of plasma urate In other words, if plasma urate begins to increase because of increased urate production, the active proximal secretion of urate is stimulated, thereby increasing urate excretion Given these mechanisms of renal urate handling, the reader should be able to deduce the 3 ways by which altered renal function can lead to decreased urate

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73 SnS( s) + 2H + (aq )

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excretion and hence increased plasma urate, as in gout: (1) decreased filtration of urate secondary to decreased GFR, (2) excessive reabsorption of urate, and (3) diminished secretion of urate

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Proximal tubules possess several closely related transport systems for organic cations that are analogous to those for organic anions: Because of the large number of different transporters, a substantial amount of foreign and endogenous substances are transported (Table 5 2), the cations compete with one another for transport, and the transporters manifest a Tm limitation Organic cations enter across the basolateral membrane via one of several uniporters, members of the OCT family (organic cation transporter), and exit into the lumen via an antiporter, which exchanges a proton for the organic cation The proximal secretion of organic cations, as for organic anions, is particularly critical for the excretion of those cations extensively bound to plasma proteins and not filterable at the renal corpuscle However, again similar to organic anions, many of the organic cations secreted by the proximal tubules are not protein bound and, therefore, also undergo glomerular filtration and tubular secretion; creatinine is a good example Finally, and again analogous to organic anions, some organic cations are not only actively secreted by the proximal tubules but also may undergo other forms of tubular handling, mainly passive reabsorption or secretion

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What is the equilibrium constant for the above reaction The successive acid dissociation con 8 19 stants for H2S are 95 10 (K a1) and 1 10 (K a2) The Ksp, the solubility product constant, 25 for SnS equals 10 10 (A) (B) (C) (D) (E)

Endogenous substances Acetylcholine Choline Creatinine Dopamine Epinephrine Guanidine Histamine Serotonin Norepinephrine Thiamine Drugs Atropine Isoproterenol Cimetidine Meperidine Morphine Procaine Quinine Tetraethyl ammonium

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