Injury, Body Composition, and Nitrogen Metabolism in the Surgical Patient

  • Naji N. Abumrad
  • Patricia E. Molina
  • John A. Rathmacher
  • Steven Nissen
Conference paper
Part of the Serono Symposia USA book series (SERONOSYMP)


Weight loss and wasting in the injured patient are multifactorial, and are due both to inadequate food intake and to excessive catabolism. The capacity to estimate change in lean body mass (LBM) in the perioperative period is limited due to the lack of appropriate methodology. Most in vivo methods currently utilized for estimating body mass and composition yield information mostly pertaining to body fat and body water. Most estimates of LBM are indirect, expensive, difficult, and complex for routine clinical and investigational use.


Body Composition Lean Body Mass Nitrogen Metabolism Branch Chain Amino Acid Total Body Water 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abe Y, Miyake M, Horiuchi A, Kumori K, Kimura S. Changes in the productivity of cytokines and active-oxygen in peripheral blood cells following surgery. Surg Today 1992; 22: 15–18.PubMedCrossRefGoogle Scholar
  2. Abumrad NN, Rabin D, Wise KL, Lacy WW. The disposal of an intravenously administered amino acid load across the human forearm. Metabolism 1982; 31: 463–70.PubMedCrossRefGoogle Scholar
  3. Aoki TT, Brennan M, Fitzpatrick GF, Knight DC. Leucine meal increases glutamine and total nitrogen release from forearm muscle. J Clin Invest 1981; 68: 1522–28.PubMedCrossRefGoogle Scholar
  4. Bachhawat BK, Robinson WG, Coon MJ. The enzymatic cleavage of beta-hydroxy-betamethylglutaryl coenzyme A to aceto-acetate and acetyl coenzyme A. J Biol Chem 1955; 216: 727–36.PubMedGoogle Scholar
  5. Bates PC, Grimble GK, Sparrow MP, Millward DJ. Myofibrillar protein turnover: synthesis of protein-bound 3-methylhistidine, actin, myosin heavy chain and aldolase in rat skeletal muscle in the fed and starved states. J Biochem 1983; 214: 593–605.Google Scholar
  6. Beg ZH, Lupien PJ. In vitro and in vivo inhibition of hepatic cholesterol synthesis by 3-hydroxy-3-methylglutaric acid. Biochim Biophys Acta 1972; 260: 439–48.PubMedGoogle Scholar
  7. Benedict FG. A study of prolonged fasting. Carnegie Institute Publication No. 203. Washington, DC: Carnegie Institute, 1915.Google Scholar
  8. Bergstrom J, Beroniade V, Hultman E, Norch-Nordlund AE. Relation between glycogen and electrolyte metabolism in human muscle. In: Symposium uber Transport and Funktion intracellularer elektrolyte. Kruck SF, ed. Munich: Urban and Schwarzenberg, 1967.Google Scholar
  9. Bergstrom J, Furst P, Holmstrom B, Vinnars E, Ashkenazi J, Elwyn DH, et al. Influence of surgery and nutrition on muscle water and electrolytes. Effect of elective operations. Ann Surg 1981; 193: 810–19.PubMedCrossRefGoogle Scholar
  10. Bloch K, Clark LC, Haray I. Utilization of branched chain acids in cholesterol synthesis. J Biol Chem 1954; 211: 687–99.PubMedGoogle Scholar
  11. Blomstrand E, Hassmen E, Ekblom B, Newsholme EA. Administration of branched-chain amino acids during sustained exercise. The effects on performance and plasma concentrations of some amino acids. J Appl Physiol 1991; 68: 83–88.Google Scholar
  12. Buckspan R, Hoxworth B, Cersosimo E, Devlin J, Horton E, Abumrad NN. Alphaketoisocaproate is superior to leucine in sparing glucose utilization in humans. Am J Physiol 1986; 251: E648–53.PubMedGoogle Scholar
  13. Burns J, Cresswell E, Ell S, Fynn M, Jackson MA, Lee HA, et al. Comparison of the effects of keto acid analogues and essential amino acids on nitrogen homeostasis in uremic patients on moderately protein-restricted diets. Am J Clin Nutr 1978; 31: 1767–75.PubMedGoogle Scholar
  14. Cersosimo E, Miller BM, Lacy WW, Abumrad NN. Alpha-ketoisocaproate, not leucine, is responsible for nitrogen sparing during progressive fasting in normal male volunteers. Surg Forum 1983; 34: 96–99.Google Scholar
  15. Choo PS, Smith TK, Cho CY, Ferguson HW. Dietary excesses of leucine influence growth and body composition of rainbow trout. J Nutr 1991; 121: 1932–39.PubMedGoogle Scholar
  16. Chua B, Siehl DL, Morgan HE. Effect of leucine and metabolites of branched chain amino acids on protein turnover in heart. J Biol Chem 1979; 254: 8358–62.PubMedGoogle Scholar
  17. Cuthbertson DP. Observations on the disturbance of metabolism produced by injury to the limbs. Q J Med 1932; 1: 237–51.Google Scholar
  18. Cuthbertson DP. The metabolic response to injury and its nutritional implications: retrospect and prospect. JPEN 1979; 3: 108–29.Google Scholar
  19. Duran M, Ketting D, Wadman SK, Jakobs C, Schutgens RBH, Veder HA. Organic acid excretion in a patient with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency: facts and artefacts. Clin Chim Acta 1978; 90: 187–93.PubMedCrossRefGoogle Scholar
  20. Eriksson LS, Hagenfeldt L, Wahren J. Intravenous infusion of a-oxoisocaproate: influence on amino acid and nitrogen metabolism in patients with liver cirrhosis. Clin Sci 1982; 62: 285–93.PubMedGoogle Scholar
  21. Eriksson LS, Conn HO. Branched-chain amino acids in hepatic encephalopathy. Gastroenterology, 1990; 99: 604–5.Google Scholar
  22. Finn PJ, Plank LD, Clark MA, Connolly AB, Hill GL. Progressive cellular dehydration and proteolysis in critically ill patients. Lancet 1996; 347: 654–56.PubMedCrossRefGoogle Scholar
  23. Flakoll PJ, Kulaylat M, Frexes-Steed M, Hourani H, Brown LL, Hill JO, et al. Amino acids augment insulin’s suppression of whole body proteolysis. Am J Physiol 1989; 257: E839–47.PubMedGoogle Scholar
  24. Frexes-Steed M, Warner ML, Bulus N, Flakoll P, Abumrad NN. Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting. Am J Physiol 1990; 258: E907–17.PubMedGoogle Scholar
  25. Frexes-Steed M, Lacy DB, Collins J, Abumrad NN. Role of leucine and other amino acids in regulating protein metabolism in vivo. Am J Physiol 1992; 262: E925–35.PubMedGoogle Scholar
  26. Garibaldo RA, Britt MR, Coleman ML, Reading JC, Pace NL. Risk factors for the development of postoperative pneumonia. Am J Med 1981; 70: 677–80.CrossRefGoogle Scholar
  27. Grande F, Keys A. Body weight composition and calorie status. In: Modern nutrition in health and disease. Philadelphia: Lea & Febiger, 1980: 3–34.Google Scholar
  28. Harbhajan PS, Siamak AA. Leucine oxidation in diabetes and starvation: effects of ketone bodies on branched chain amino acid oxidation in vitro. Metabolism 1978; 27: 185–200.CrossRefGoogle Scholar
  29. Haydock DA, Hill GL. Impaired wound healing in surgical patients with varying degrees of malnutrition. JPEN 1987; 10: 550–54.Google Scholar
  30. Hider RC, Fern EB, London DR. Relationship between intracellular amino acids and protein synthesis in the extensor digitorum longus muscle of rats. J Biochem 1960; 114: 171–78.Google Scholar
  31. Hill GL. Body composition research at the University of Auckland. Some implications for modern surgical practice. Aust NZ J Surg 1988; 58: 13–21.CrossRefGoogle Scholar
  32. Hokland BM, Bremer J. Formation and excretion of branched-chain acylcarnitines and branched-chain hydroxy acids in the perfused rat kidney. Biochim Biophys Acta 1988; 961: 30–37.PubMedGoogle Scholar
  33. Keim NL, Mayclin PL, Taylor SF, Brown DL. Total-body electrical conductivity method for estimating body composition: validation by direct carcass analysis of pigs 1–4. Am J Clin Nutr 1988; 47: 180–85.PubMedGoogle Scholar
  34. Kinney JM. The tissue composition of surgical weight loss. In: Advances in parenteral nutrition. Johnson IDA, ed. Lancaster, England: MTP 1978: 511–20.Google Scholar
  35. Krebs HA, Lund P. Aspects of the regulation of the metabolism of branched-chain amino acids. Adv Enz Reg 1977; 15: 375–94.CrossRefGoogle Scholar
  36. Kuhlman G, Roth JA, Flakoll PJ, Vandehaar MJ, Nissen S. Effects of dietary leucine, a-ketoisocaproate and isovalerate on antibody production and lymphocyte blastogenesis in growing lambs. J Nutr 1988; 118: 15649.Google Scholar
  37. Long CLL, Haverberg N, Young VR, Kinney JM, Munro HN, Geiger JW. Metabolism of 3-methylhistidine in man. Metabol 1975; 24: 929–35.CrossRefGoogle Scholar
  38. Long CLL, Dillard DR, Bodzin JH, Geiger JW, Blakemore WS. Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans. Metabolism 1988; 37: 844–49.PubMedCrossRefGoogle Scholar
  39. Marchesini G, Zoli M, Dondi C, Bianchi G, Cirulli M, Pisi E. Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis. Hepatology 1982; 2: 420–25.PubMedCrossRefGoogle Scholar
  40. Mathias MM, Sullivan AC, Hamilton JG. Fatty acid and cholesterol synthesis from specifically labeled leucine by isolated rat hepatocytes. Lipids 1981; 16: 739–43.PubMedCrossRefGoogle Scholar
  41. Miles JM, Nissen SL, Rizza RA, Gerischj JE, Haymond MW. Failure of infused ßhydroxybutyrate to decrease proteolysis in man. Diabetes 1983; 32: 197–205.PubMedCrossRefGoogle Scholar
  42. Mitch WE, Walser M, Sapir D. Nitrogen sparing induced by leucine compared with that induced by its keto analog-ketoisocaproate in fasting obese man. J Clin Invest 1981; 67: 553–62.PubMedCrossRefGoogle Scholar
  43. Mock DM, Mock NI, Weintraub S. Abnormal organic aciduria in biotin deficiency: the rat is similar to the human. J Lab Clin Med 1988; 112: 240–47.PubMedGoogle Scholar
  44. Molina PE, Ajmal M, Abumrad NN. Energy metabolism and fuel mobilization; from the perioperative period to recovery. Shock 1998; 9: 241–48.PubMedCrossRefGoogle Scholar
  45. Monk DN, Plank LD, Frach-Arcas G, Finn PJ, Streat SJ, Hill GL. Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma. Ann Surg 1996; 223: 395–405.PubMedCrossRefGoogle Scholar
  46. Moore FD, Olesen KH, McMurrey JD, Parker HV, Ball MR, Boyden CM. The body cell mass and its supporting environment. Philadelphia/London: W.B. Saunders Company, 1963.Google Scholar
  47. Morgan HE, Chua BH, Boyd T, Jefferson LS. Branched chain amino acids and the regulation of protein turnover in heart and skeletal muscle. In: Metabolism and clinical implications of branched chain amino and ketoacids. Walser M, Williamson JR, eds. New York: Elsevier North Holland, 1981: 217–26.Google Scholar
  48. Mortimore GE, Poso AR, Kadowaki M, Wert JJ Jr. Multiphasic control of hepatic protein degradation by regulatory amino acids. J Biol Chem 1987; 262: 16322–27.PubMedGoogle Scholar
  49. Nair KS, Welle SL, Halliday DJ, Campbell RG. Effect of ß-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J Clin Invest 1988; 82: 198–205.PubMedCrossRefGoogle Scholar
  50. Nissen SL, Van Koevering M, Webb D. Analysis of β-hydroxy-β-methyl butyrate in plasma by gas chromatography and mass spectrometry. Anal Biochem 1990; 88: 17–19.CrossRefGoogle Scholar
  51. Nissen SL, Sharp R, Rathmacher JA, Rice J, Fuller JC Jr, Connelly AS, et al. The effect of the leucine metabolite (3-hydroxy ß-methylbutyrate on muscle metabolism during resistance-exercise training. J Appl Physiol 1996; 81: 2095–104.PubMedGoogle Scholar
  52. Nissen SL, Abumrad NN. Nutritional role of the leucine metabolite β-hydroxy β-methylbutyrate (HMB). J Nutr Biochem 1997; 8: 300–11.CrossRefGoogle Scholar
  53. Pawan GLS, Semple SJG. Effect of 3-hydroxybutyrate in obese subjects on very low energy diets. Proc Nutr Soc 1980; 39: 48a.Google Scholar
  54. Pichard C, Kyle U, Chevrolet JC, Jolliet P, Slosman D, Mensi N, et al. Lack of effects of recombinant growth hormone on muscle function in patients requiring prolonged mechanical ventilation: a prospective, randomized, controlled study. Crit Care Med 1996; 24: 403–13.PubMedCrossRefGoogle Scholar
  55. Prior BM, Cureton KJ, Modlesky CM, Evans EM, Sloniger MA, Saunders M, Lewis RD. In vivo validation of whole body composition estimates from dual-energy X-ray absorptiometry. J Appl Physiol 1997; 83: 623–30.PubMedGoogle Scholar
  56. Rathmacher JA, Flakoll PJ, Nissen SL. A compartmental model of 3-methylhistidine metabolism in humans. Am J Physiol 1995; 269: E193–98.PubMedGoogle Scholar
  57. Rosenthal J, Angel A, Farkus J. Metabolic fate of leucine: a significant sterol precursor in adipose tissue and muscle. Am J Physiol 1974; 226: 411–18.PubMedGoogle Scholar
  58. Sanbourin PJ, Bieber LL. Formation of β-hydroxyisovalerate from α-ketoisocaproate by a soluble preparation from rat liver. Dev Biochem 1981; 18: 149–54.Google Scholar
  59. Sandstrom R, Svanberg E, Hyltander A, Haglind E, Ohlsson C, Zachrisson H, et al. The effect of recombinant human IGF-I on protein metabolism in post-operative patients without nutrition compared to effects in experimental animals. Eur J Clin Invest 1995; 25: 784–92.PubMedCrossRefGoogle Scholar
  60. Sax HC, Talamini MA, Fischer JE. Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns. Arch Surg 1986; 121: 358–66.PubMedGoogle Scholar
  61. Sjölin J, Stjernström H, Friman G, Larsson J, Wahren J. Total and net muscle protein breakdown in infection determined by amino acid effluxes. Am J Physiol 1990; 258: E856–63.PubMedGoogle Scholar
  62. Smith TK. Effect of leucine-rich dietary protein on in vitro protein synthesis in porcine muscle. Proc Soc Exp Biol Med 1985; 180: 538–43.PubMedGoogle Scholar
  63. Tanaka K, Isselbacher ICJ. Experimental beta-hydroxyisovaleric aciduria induced by biotin deficiency. Lancet 1970; 31: 930–31.CrossRefGoogle Scholar
  64. Tischler ME, Desautels M, Goldberg AL. Does leucine, leucyl-trna, or some metabolite of leucine regulate protein synthesis and degradation in skeletal and cardiac muscle? J Biol Chem 1981; 257: 1613–21.Google Scholar
  65. Van Koevering M, Nissen S. Oxidation of leucine and a-ketoisocaproate to β-hydroxy-β-methylbutyrate in vivo. Am J Physiol 1992; 262: 27–31.Google Scholar
  66. Wagenmakers AJM, Salden HJM, Veerkamp JH. The metabolic fate of branched chain amino acids and 2-oxo acids in rat muscle homogenate and diaphragms. Int J Biochem 1985; 17: 957–65.PubMedCrossRefGoogle Scholar
  67. Windsor JA, Hill GL. Depleted protein stores lead to an increased complication rate after major surgery. Aust NZ J Surg 1987; 57: 259–65.Google Scholar
  68. Yarasheski KE. Growth hormone effects on metabolism, body composition, muscle mass, and strength. Exer Sport Sci Rev 1994; 22: 285–312.CrossRefGoogle Scholar
  69. Young VR, Alex SD, Baliga BS, Munro HN, Muecke H. Metabolism of administered 3-methylhistidine: lack of muscle transfer ribonucleic acid charging and quantitative excretion as 3-methylhistidine and its N-acetyl derivative. J Biol Chem 1972;217:3592–600Google Scholar
  70. Young VR, Munro HR. Nt-Methylhistidine (3-methylhistidine) and muscle protein turnover: an overview. Fed Proc 1978; 37: 2291–300.PubMedGoogle Scholar
  71. Yu W, Kuhara T, Inoue Y, Matsumoto I, Iwasaki R, Morimoto S. Increased urinary excretion of β-hydroxyisovaleric acid in ketotic and nonketotic type II diabetes mellitus. Clin Chim Acta 1990; 188: 161–68.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 2000

Authors and Affiliations

  • Naji N. Abumrad
  • Patricia E. Molina
  • John A. Rathmacher
  • Steven Nissen

There are no affiliations available

Personalised recommendations