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Studies on the pathophysiology of acute renal failure

II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride

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Virchows Archiv B

Summary

Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgCl2 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzymes studied were alkaline phosphatase, 5′-nucleotidase, acid phosphatase, α-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5′-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and α-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta.

These results support the hypothesis that Hg+ +, when given in a sublethal dose, is associated with early histochemical changes in the brush border of the proximal tubule, which may be related to early changes in sodium reabsorption and to the subsequent development of acute renal failure. The observation that changes in plasma membrane-associated enzymes occur early and prior to alterations in enzymes of mitochondria and the endoplasmic reticulum suggests that Hg++ interacts initially with the plasma membrane.

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Authors and Affiliations

  1. Department of Pathology, School of Medicine, University of Maryland, 31 S. Greene Street, 21201, Baltimore, Maryland, USA

    R. C. Zalme, E. M. McDowell & B. F. Trump

  2. Department of Pathology, University of Arizona Medical Center, 85721, Tucson, Arizona, USA

    R. B. Nagle

  3. Department of Nephrology, Division of Medicine, Walter Reed Army Institute of Research, 20012, Washington, D.C., USA

    J. S. McNeil

  4. Nephrology Service, Veterans Administration Hospital, 150 South Huntington Avenue, 02130, Boston, Massachusetts, USA

    W. Flamenbaum

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  1. R. C. Zalme
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  2. E. M. McDowell
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  3. R. B. Nagle
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  4. J. S. McNeil
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  5. W. Flamenbaum
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  6. B. F. Trump
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Submitted in partial fulfillment of a Master of Science degree from the Department of Pathology, University of Maryland Medical School, Baltimore, Maryland

This is contribution #328 from the Cellular Pathobiology Laboratory

This work was supported by Grant #DAMD-17-75-C-5010 from the USARDC

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Zalme, R.C., McDowell, E.M., Nagle, R.B. et al. Studies on the pathophysiology of acute renal failure. Virchows Arch. B Cell Path. 22, 197–216 (1976). https://doi.org/10.1007/BF02889216

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