Summary
Since abnormalities in the renal handling of sodium and water in both the proximal and distal tubule have been described in primary hypothyroidism, this study was undertaken to examine renal tubular hydrogen secretion in this disorder. Metabolic acidosis was induced in hypothyroid rats (H) and their age matched controls (C) by the administration of an oral ammonium chloride load of 0.15 g/24 h/kg for three days. On day 3 animals were prepared for clearance and acid-base studies, receiving an infusion of Ringer's solution of 0.6 ml/hr/100 g during surgery and the experimental procedure. A 26% decrease in GFR (P<0.005) and a doubling in fractional excretion of sodium (P<0.02) were observed in H rats. The lowest blood pH and average bicarbonate concentration and the excretion of chloride were similar in the two groups, indicating that the acid load was reabsorbed and led to similar degrees of systemic acidification. Urine flow also was comparable in the two groups. Minimal urine pH after NH4Cl was 6.21±0.06 in H and 5.68±0.09 in C (P<0.001). Ammonium excretion was 28% (P<0.05) lower in H than in C. The defect in urine acidification in H was only partially corrected after 5 days on a low sodium diet and DOCA administration for 2 days. Fractional bicarbonate excretion at normal blood pH and bicarbonate concentration was not different in the two groups. These data indicate that hypothyroid rats have a mild defect in urine acidification and that it is localized predominantly in the distal tubule.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Better, O. S., Goldschmid, Z., Chaimowitz, C., Alroy, G. G.: Defect in urinary acidification in cirrhosis (The role of excessive tubular reabsorption of sodium in its etiology). Arch. intern. Med.130, 77–83 (1972)
Ekins, R. P.: The estimation of thyroxine in human plasma by an electrophoretic technique. Clin. chim. Acta5, 453–459 (1960)
Emmanouel, D. S., Lindheimer, M. D., Katz, A. I.: Mechanism of impaired water excretion in the hypothyroid rat. J. clin. Invest.54, 926–934 (1974)
Fregly, M. J., Brimhall, R. L., Galindo, O. J.: Effect of the antithyroid drug propylthiouracil on the sodium balance of rats. Endocrinology71, 693–700 (1962)
Fregly, M. J., Cade, J. R., Waters, I. W., Straw, J. A., Taylor, R. E.: Secretion of aldosterone by adrenal glands of propylthiouracil-treated rats. Endocrinology77, 777–784 (1965)
Giebisch, G., Malnic, G., Klose, R. M., Windhager, E. E.: Effect of ionic substitutions on distal potential difference in the rat kidney. Amer. J. Physiol.211, 560–568 (1966)
Hills, A. G., Reid, E. L.:\(P_{{\text{CO}}_2 } \) and\(P_{{\text{NH}}_3 } \) in mammalian kidney and urinary tract related to urine pH and flow. Amer. J. Physiol.219, 423–434 (1970)
Holmes, E. W., Jr., DiScala, V. A.: Studies on the exaggerated natriuretic response to a saline infusion in the hypothyroid rat. J. clin. Invest.49, 1224–1236 (1970)
Huth, E. J., Mayock, R. L., Kerr, R. M.: Hyperthyroidism associated with renal tubular acidosis. (Discussion of possible relationship). Amer. J. Med.26, 818–826 (1959)
Kadenbach, B.: Effect of thyroid hormones on mitochondrial enzymes. In: Regulation of metabolic processes in mitochondria, J. R. Tager, ed., pp. 508–517. Amsterdam: Elsevier 1966
Kurtzman, N. A., White, M. G., Rogers, P. W.: Aldosterone deficiency and renal bicarbonate reabsorption. J. Lab. clin. Med.77, 931–940 (1971)
Luetscher, J. A., Cohn, A. P., Camargo, C. A., Dowdy, A. J., Callaghan, A. M.: Aldosterone secretion and metabolism in hyperthyroidism and myxedema. J. clin. Endocr.23, 873–880 (1963)
Malnic, G., Giebisch, G.: Mechanism of renal hydrogen ion secretion. Kidney Int.1, 280–296 (1972)
Mason, A. M. S., Golding, P. L.: Hyperglobulinaemic renal tubular acidosis: A report on nine cases. Brit. med. J.III, 143–146 (1970)
Michael, U. F., Barenberg, R. L., Chavez, R., Vaamonde, C. A., Papper, S.: Renal handling of sodium and water in the hypothyroid rat. (Clearance and micropuncture studies). J. clin. Invest.51, 1405–1412 (1972)
Michael, U. F., Kelley, J., Alpert, H., Vaamonde, C. A.: Impaired renal diluting capacity in the hypothyroid rat with hereditary diabetes insipidus. Kidney Int.6, 76A (1974)
Murphy, B. E. P., Pattee, C. J.: Determination of thyroxine utilizing the property of protein binding. J. clin. Endocr.24, 187–196 (1964)
Osorio, J. A., Zadunaisky, J. A.: Clearances de inulina y diodrast y peso renal en ratas tratadas con I131 y polvo de tiroides. Rev. Soc. argent. Biol.32, 195–203 (1956)
Oster, J. R., Hotchkiss, J. L., Carbon, M., Vaamonde, C. A.: Abnormal renal acidification in alcoholic liver disease. J. Lab. clin. Med.85, 451–466 (1975)
Read, A. E., Sherlock, S., Harrison, C. V.: Active ‘juvenile’ cirrhosis considered as part of a systemic disease and the effect of corticosteroid therapy. Gut4, 378–393 (1963)
Rector, F. C., Jr.: Micropuncture studies on the mechanism of urinary acidification. In: Renal metabolism and epidemiology of some renal diseases, pp. 9–31. York, Pennsylvania: Maple Press 1964
Sartorius, O. W., Calhoon, D., Pitts, R. F.: Studies on the inter-relationships of the adrenal cortex and renal ammonia excretion by the rat. Endocrinology.52, 256–265 (1953)
Seligson, D., Seligson, H.: A microdiffusion method for the determination of nitrogen liberated as ammonia. J. Lab. clin. Med.38, 324–330 (1951)
Snedecor, G. W., Cochran, W. G.: Statistical methods, 6th Ed. Ames: The Iowa State University Press 1968
Stéphan, F., Jahn, H., Réville, P.: Action de l'insuffisance thyroidienne sur la survie du rat surrénalectomisé. C. R. Acad. Sci. (Paris)251, 1666–1668 (1960)
Stéphan, F., Réville, P., Jahn, H.: Etude expérimentale des effets de l'hypothyroidisme sur le pouvoir de concentration et de dilution du rein. J. Urol. Néphrol.72, 849–872 (1966)
Szezepski, O., Walczak, M., Bittner, K., Maciejewski, J., Szekalski, S., Korman, E.: The behaviour of indices of acidbase equilibrium in children with hypothyroidism. Endokr. pol.21, 125–131 (1970)
Talal, N., Zisman, E., Schur, P. H.: Renal tubular acidosis, glomerulonephritis and immunologic factors in Sjögren's syndrome. Arth. and Rheum.11, 774–786 (1968)
Tannen, R. L.: The relationship between urine pH and acid excretion—the influence of urine flow rate. J. Lab. clin. Med.74, 757–769 (1969)
Wrong, O., Davies, H. E. F.: The excretion of acid in renal disease. Quart. J. Med.28, 259–313 (1959)
Zisman, E., Buccino, R. A., Gorden, P., Bartter, F. C.: Hyperthyroidism and renal tubular acidosis. Arch. intern. Med.121, 118–122 (1968)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Michael, U.F., Chavez, R., Cookson, S.L. et al. Impaired urinary acidification in the hypothyroid rat. Pflugers Arch. 361, 215–220 (1976). https://doi.org/10.1007/BF00587285
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00587285