924 7. MERCURIALS 



mercurials, I am not convinced that it is more important than resorption 

 from the glomerular filtrate. If 1-5% of the total plasma mercurial is in a 

 freely diffusible form, this fraction will certainly be filtered readily and 

 concentrated in the lumen; renal accumulation occurs with many drugs 

 which are bound to the plasma proteins. Second, only the free mercurial is 

 available to the tubular cells from the peritubular fluid, and it is difiicult 

 to envision a mechanism by which the cells can pick up or actively secrete 

 protein-bound mercurial. The tubular cells undoubtedly accumulate mer- 

 curials from the plasma as do other tissues, and may secrete them to some 

 extent, but the rates of excretion are not such as to imply secretion as the 

 major pathway. It is also strange that mecurials of so many different struc- 

 tures would be actively secreted; those with carboxylate groups might be 

 carried by the transport system for acids, as Campbell (1959) postulated 

 for mercaptomerin, but neither probenecid nor p-aminohippurate interferes 

 with the excretion of mercurials in the dog (Kessler et al., 1957 b). In any 

 event, there is little likelihood that the pattern of mercurial distribution in 

 the kidney can be directly correlated with the site of action. Weiner et al. 

 (1959) emphasized that there is no obvious relationship between diuresis 

 and the total amount of mercurial in the kidney or its parts, and stated, 

 "Diuresis is a consequence of the action on a specific renal receptor by a 

 very small amount of mercury." 



(E) Stop-flow technique. Serial sampling of urine following ureteral clamp- 

 ing allows an analysis of the composition changes throughout the nephron, 

 and such studies have uniformly pointed to a proximal rather than a distal 

 site of mercurial action (Kessler et al., 1958; Vander et al., 1958). This ap- 

 plies exclusively to the site of inhibition of Na+ resorption and diuresis. 



(F) Differential damage to renal cells. It has been thought that those por- 

 tions of the nephron most readily damaged by toxic doses of the mercurials 

 might be the same portions primarily affected to produce diuresis. Suzuoki 

 (1912) was the first to show by adequate methods that mercurials can dam- 

 age rather selectively the more terminal portions of the proximal tubules. 

 Edwards (1942), on the other hand, claimed that Hg++ exerts selective 

 damage on the central region of the proximal convoluted tubule, injury 

 to the distal convolution being rarely seen. The loops of Henle are too thin 

 and squamous to permit satisfactory examination. Simonds and Hepler 

 (1945) confirmed the observations of Suzuoki in finding selective damage 

 to terminal proximal tubules. More recent work has not greatly extended 

 our knowledge. Relatively little damage to the glomeruli has been confirm- 

 ed (Staemmler, 1956) even when a severe nephrosis is produced, although 

 Schorcher and Loblich (1960) found some changes in the glomerular filtra- 

 tion membrane by electron microscopy. Tubular cells show apical edema 

 and vacuolization, these occurring primarily in the proximal segment in 

 rats injected with meralluride (Sanabria, 1963). The brush border may show 



