The Myopathy of Phosphate Depletion

  • Nachman Brautbar
  • Shaul G. Massry
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 178)


Phosphate depletion is commonly associated with proximal muscle weakness, muscle pain, impaired resting membrane potential (1) and mild elevation of creatine phosphokinase and aldolase (1). Phosphorus depletion in experimental animals has been shown to cause severe muscle weakness and creatinuria (2). Fuller and associates (1) examined the effect of phosphate depletion and repletion on skeletal muscle in the dog; they found that resting muscle membrane potential and muscle content of potassium and total phosphorus fell, while muscle sodium, chloride and water content rose with phosphate depletion. All these abnormalities returned to, or towards, normal with phosphate repletion. Further studies by the same group of investigators demonstrated that overt rhabdomyolysis may be precipitated by the superimposition of severe hypophosphatemia on pre-existing subclinical myopathy (3). In addition, a rise in creatine phosphokinase occurs in patients who develop acute fall in the serum levels of phosphorus (4). The observation that myopathic symptoms develop only in severe hypophosphatemia (4), and that acute hypophosphatemia may be associated With acute rhabdomyolysis suggest that both serum and cellular inorganic phosphorus levels play an important role in the myopathy.


Creatine Phosphate Inorganic Phosphorus Creatine Phosphokinase Ethanolamine Phosphatidyl Mitochondrial Oxygen Consumption 
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  1. 1.
    T.J. Fuller, N.W. Carter, C. Barcenas, J.P. Knochel, Reversible changes of the muscle cell in experimental phosphorus deficiency, J. Clin. Invest. 57: 1019 (1976).PubMedCrossRefGoogle Scholar
  2. 2.
    H. Schneider and H. Steenbock, A low phosphate diet and the response of rats to vitamin D, J. Biol. Chem. 128: 159 (1939).Google Scholar
  3. 3.
    J.P. Knochel, C. Barcenas, J.R. Cotton, Hypophosphatemia and rhabdomyolysis, J. Clin. Invest. 62: 1240 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    J.P. Knochel, Hypophosphatemia, West. J. Med. 134: 15 (1981).Google Scholar
  5. 5.
    N. Brautbar, R. Baczynski, C. Carpenter, S. Moser, P. Geiger, P. Einander, S.G. Massry, Impaired energy metabolism in rat myocardium during phosphate depletion, Amer. J. Physio. 242: F699 (1982).Google Scholar
  6. 6.
    R.J. Solaro, D.C. Panyg, F.N. Briggs, The purification of cardiac myofibrils with triton X-100. Biochem. Biophys. Acta 245: 259 (1971).PubMedCrossRefGoogle Scholar
  7. 7.
    Methods of Enzymatic Analysis. Editor: H.W. Bergmeyer, Volume I, pp. 473–474, Academic Press, Inc., New York, 1974.Google Scholar
  8. 8.
    E.G. Bligh and E.G. Dyer, A rapid method of total lipid extraction and purification, Can. J. Physiol. 37: 911 (1959).Google Scholar
  9. 9.
    N. Brautbar, J. Tabernero-Romo, J. Coats, S.G. Massry, Impaired myocardial lipid metabolism in phosphate depletion, Kidney Int. (In Press).Google Scholar
  10. 10.
    J.K. Kaitaranta and S.P. Bessman, Determination of phospholipids by a combined liquid chromatography-automated phosphorus analyzer, Anal. Chem. 53: 1232 (1981).Google Scholar
  11. 11.
    G.R. Barlett; Phosphorus assay in column chromatography, J. Biol. Chem. 234: 466 (1959).Google Scholar
  12. 12.
    R.L. Veech, W.R. Lawson, N.W. Cornell, Cytosolic phosphorylation potential, J. Biol. Chem. 254: 6538 (1979).PubMedGoogle Scholar
  13. 13.
    S.P. Bessman and P.J. Geiger: Transport of energy in muscle: The phosphorylcreatine shuttle, Science. 211: 448 (1981).PubMedCrossRefGoogle Scholar
  14. 14.
    M. Erecinska, M. Stubbs, Y. Miyaa, Regulation of cellular metabolism by intracellular phosphate, Biochem. Biophys. Acta. 462: 20 (1977).CrossRefGoogle Scholar
  15. 15.
    B.D. Hettleman, R.L. Sabina, M.K. Drezner, E.W. Holmes, J.L. Swain, Defective adenosine triphosphate synthesis. An explanation for skeletal muscle dysfunction in phosphate deficient mice, J. Clin. Invest. 72: 582, 1983.PubMedCrossRefGoogle Scholar
  16. 16.
    R.A. DeFronzo and R. Lang, Hypophosphatemia and glucose intolerance: Evidence for tissue insensitivity to insulin, New Engl. J. Med. 303: 1259 (1980).Google Scholar
  17. 17.
    J.L. Davis, S.B. Lewis, T.A. Schultz, R.A. Kaplan, J.D. Wallin, Acute and chronic phosphate depletion as a modulator of glucose uptake in rat skeletal muscle, Life Science, 24: 629 (1979).CrossRefGoogle Scholar
  18. 18.
    W.H. Hori, W. Kreusser, A. Heidland, E. Ritz, Abnormalities of glycogen metabolism in cardiomyopathy of phosphorus depletion. In: Phosphate and Minerals in Health and Disease. Editors: S.G. Massry, E. Ritz, and H. Jahn, pp. 343–350, Plenum Press, New York, 1980.Google Scholar
  19. 19.
    L.N. Gold, S.G. Massry, R.M. Friedler, Effects of phosphate depletion on renal tubular reabsorption of glucose, J. Lab. Clin. Med 89: 554 (1977).PubMedGoogle Scholar
  20. 20.
    V.M. Campese, Y. Saglikes, N. Brautbar, R. Brandt, S.G. Massry, Effect of phosphate depletion on blood pressure, Proceedings of the Amer. Soc. Nephrol, p 4A (1982).Google Scholar
  21. 21.
    W. Kreusser, H. Scholz, W. Rascher, A. Schomig, R. Dietz, D. Klormann, E. Ritz, Circulatory response to pressor agents in phosphorus depletion. In: Regulation of Phosphate and Mineral Metabolism. Ed. S.G. Massry, J. Letteri, E. Ritz, Plenum Press, New York, 1982, pp. 259–266.CrossRefGoogle Scholar
  22. 22.
    C.L. Carpenter, C. Mohan, P.S. Bessman, Inhibition of protein and lipid synthesis in muscle by 2,4 dinitroflurobenzene, an inhibitor of creatine phosphokinase, Biochem. Biophys. Res. Com. 111: 884 (1983).CrossRefGoogle Scholar
  23. 23.
    Seraydarian, M.W. and L. Artaza, Regulation of energy metabolism by creatine in cardiac and skeletal muscle cells in culture, J. Mol. Cell. Cardiol. 8: 669 (1976).CrossRefGoogle Scholar
  24. 24.
    V.A. Saks, V.V. Kupriyanov, G. Elizarova, Studies of energy transport in heart cells, J. Biol. Chem. 255: 755 (1980).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Nachman Brautbar
    • 1
  • Shaul G. Massry
    • 1
  1. 1.Division of NephrologyUniversity of Southern California, School of MedicineLos AngelesUSA

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