Infection, Bacteremia, Sepsis, and the Sepsis Syndrome: Metabolic Alterations, Hypermetabolism, and Cellular Alterations

  • Matthias Majetschak
  • Christian Waydhas

Abstract

The term “sepsis syndrome” describes a systemic inflammatory and hypermetabolic response of the body on the cellular, organ, and organ systems level to a variety of microbial stimuli and to stimuli other than exogenous microbial agents. The latter may include but are not limited to accidental blunt and penetrating injuries, surgical trauma, burns, pancreatitis, inflammatory bowel disease, and others. If bacteria, viruses, or fungi are involved and the sepsis syndrome is caused by these microbes, the term “sepsis” is used. Systemic inflammatory response syndrome (SIRS) is an expression that has been used recently as a common denominator for such inflammatory states independent of their cause. Infection denotes a (locally confined) inflammatory response to the presence of microorganisms or the invasion of normally sterile host tissue by those organisms, and the term “bacteremia” means the presence of bacteria in the bloodstream, indicating an infectious focus with spillover of bacteria into the circulation. Conditions such as viremia and fungemia can be similarly defined.1, 2

Keywords

Lactate Lipase Cortisol Pancreatitis Glutamine 

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References

  1. 1.
    American College of Chest Physicians—Society of Critical Care Medicine Consensus Conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20: 864.CrossRefGoogle Scholar
  2. 2.
    Beal AL, Cerra FB: Multiple organ failure syndrome in the 1990s. systemic inflammatory response and organ dysfunction. JAMA 1994; 271: 222.CrossRefGoogle Scholar
  3. 3.
    Nguyen TT, Gilpin DA, Meyer NA, et al: Current treatment of severely burned patients. Ann Surg 1996; 223: 14.PubMedCrossRefGoogle Scholar
  4. 4.
    Frankenfield DC, Smith JS, Cooney RN, et al: Relative association of fever and injury with hypermetabolism in critically ill patients. Injury 1997; 28: 617.PubMedCrossRefGoogle Scholar
  5. 5.
    Chiolero R, Revelly JP, Tappy L: Energy metabolism in sepsis and injury. Nutrition 1997; 13: 45S.PubMedCrossRefGoogle Scholar
  6. 6.
    Jeevanandam M, Young D, Schiller W: Obesity and the metabolic response to severe multiple trauma in man. J Clin Invest 1991; 87: 262.PubMedCrossRefGoogle Scholar
  7. 7.
    Wilmore D, Orcutt T, Mason A, et al: Alterations in hypothalamic function following thermal injury. J Trauma 1975; 15: 697.PubMedCrossRefGoogle Scholar
  8. 8.
    Viale J, Annat GJ, Bouffard Y, et al: Oxygen cost of breathing in postoperative patients: pressure support ventilation vs. continuous positive airway pressure. Chest 1988; 93: 506.PubMedCrossRefGoogle Scholar
  9. 9.
    Boyd O, Grounds M, Bennett D: The dependency of oxygen consumption on oxygen delivery in critically ill postoperative patients is mimicked by variations in sedation. Chest 1992; 101: 1619.PubMedCrossRefGoogle Scholar
  10. 10.
    Edwards J, Brown G, Nightingale P: Use of survivors’ cardiorespiratory values as therapeutic goals in septic shock. Crit Care Med 1989; 17: 1098.PubMedCrossRefGoogle Scholar
  11. 11.
    Allard J, Jeejheebhony K, Whitwell J, et al: Factors influencing energy expenditure in patients with bums. J Trauma 1988; 28: 199.PubMedCrossRefGoogle Scholar
  12. 12.
    Giovannini I, Boldrini G, Castagnato M, et al: Respiratory quotient and patterns of substrate utilization in human sepsis and trauma. J Parenter Enteral Nutr 1983; 7: 226.CrossRefGoogle Scholar
  13. 13.
    Elwyn DH, Kinney JM, Juvanandum M: Influence of increasing carbohydrate intake on glucose kinetics in injured patients. Ann Surg 1979; 190: 117.PubMedCrossRefGoogle Scholar
  14. 14.
    Carpentier Y, Askanazi J, Elwyn D, et al: The effect of carbohydrate intake on lipolysis rate in depleted patients. Metabolism 1980; 29: 974.PubMedCrossRefGoogle Scholar
  15. 15.
    Weissman C, Kemper M: Assessing hypermetabolism and hypometabolism in the postoperative critically ill patient. Chest 1992; 102: 1566.PubMedCrossRefGoogle Scholar
  16. 16.
    Frankenfield D, Wiles CB, Bagley S, et al: Relationships between resting and total energy expenditure in injured and septic patients. Crit Care Med 1994, 22: 1796.PubMedGoogle Scholar
  17. 17.
    Hill GL: Implications of critical illness, injury, and sepsis on lean body mass and nutritional needs. Nutrition 1998; 14: 557.PubMedCrossRefGoogle Scholar
  18. 18.
    Kreymann G, Grosser S, Buggisch P, et al: Oxygen consumption and resting metabolic rate in sepsis, sepsis syndrome, and septic shock. Crit Care Med 1993; 21: 1021.CrossRefGoogle Scholar
  19. 19.
    Du Bois EF: The basal metabolism of fever. JAMA 1921; 77: 352.CrossRefGoogle Scholar
  20. 20.
    Klein S, Peters E, Shangraw R: Lipolytic response to metabolic stress in critically ill patients. Crit Care Med 1991; 19: 776.PubMedCrossRefGoogle Scholar
  21. 21.
    Elwyn D: Carbohydrate metabolism and requirements for nutritional support. Nutrition 1993; 9: 50.PubMedGoogle Scholar
  22. 22.
    Cerra FB: Hypermetabolism, organ failure, and metabolic support. Surgery 1987; 101: 1.PubMedGoogle Scholar
  23. 23.
    Wolfe RR: Substrate kinetics in sepsis. In: Little RA, Frayn KN (eds) The Scientific Basis for the Care of the Critically III Patient. Manchester, Manchester University Press, 1986; 123.Google Scholar
  24. 24.
    Imamura M, Clowes GH, Blackburn G: Liver metabolism and gluconeogenesis in trauma and sepsis. Surgery 1975; 77: 868.PubMedGoogle Scholar
  25. 25.
    Rich AJ, Wright PD: Ketosis and nitrogen excretion in undernourished surgical patients. J Parenter Enteral Nutr 1979; 3; 250.CrossRefGoogle Scholar
  26. 26.
    Burke JF, Wolfe R, Mullaney J: Glucose requirements and possible hepatic and respiratory abnormalities following excessive glucose intake. Ann Surg 1979; 190: 274.PubMedCrossRefGoogle Scholar
  27. 27.
    Long C, Kinney J, Geiger J: Nonsuppressibility of gluconeogenesis in septic patients. Metabolism 1976; 25: 193.PubMedCrossRefGoogle Scholar
  28. 28.
    Shizgal HM: Body composition and nutritional support. Surg Clin North Am 1981; 61: 729.PubMedGoogle Scholar
  29. 29.
    Wolfe RR, Jahoor F, Hartl WH: Protein and amino acid metabolism after injury. Diabetes Metab Rev 1989; 5: 149.PubMedCrossRefGoogle Scholar
  30. 30.
    Streat SJ, Beddoe AH, Hill GL: Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J Trauma 1987; 27: 262.PubMedCrossRefGoogle Scholar
  31. 31.
    Cahill GFJ: Starvation in man. N Engl J Med 1970; 282: 668.PubMedCrossRefGoogle Scholar
  32. 32.
    Biolo G, Maggi SP, Fleming RYD, et al: Relationship between transmembrane amino acid transport and protein kinetics in muscle tissue of severely burned patients. Clin Nutr 1993; 12: 4.CrossRefGoogle Scholar
  33. 33.
    Birkhahn RH, Long CL, Fitkin D, et al: Effects of major skeletal trauma on whole body protein turnover in man measured by L-[1, 14C]-leucine. Surgery 1980; 88: 294.PubMedGoogle Scholar
  34. 34.
    Petersen SR, Holaday NJ, Jeevanandam M: Enhancement of protein synthesis efficiency in parenterally fed trauma victims by adjuvant recombinant human growth hormone. J Trauma 1994; 36: 726.PubMedCrossRefGoogle Scholar
  35. 35.
    Jennissen HP: Ubiquitin and the enigma of intracellular protein degradation. Eur J Biochem 1995: 231: 1.PubMedCrossRefGoogle Scholar
  36. 36.
    Hasselgren PO, Fischer JE: Sepsis: stimulation of energy-dependent protein breakdown resulting in protein loss in skeletal muscle. World J Surg 1998; 22: 203.PubMedCrossRefGoogle Scholar
  37. 37.
    Hasselgren PO, James JH, Benson DW, et al: Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. Metabolism 1989; 38; 634.PubMedCrossRefGoogle Scholar
  38. 38.
    Zamir O, Hasselgren PO, von Allmen D, et al: The effect of interleukin-1α and the glucocorticoid receptor blocker RU 38486 on total and myofibrillar protein breakdown in the skeletal muscle. J Surg Res 1991; 50: 579.PubMedCrossRefGoogle Scholar
  39. 39.
    Hershko A, Ciechanover A: The ubiquitin system for protein degradation. Annu Rev Biochem 1992; 61: 761.PubMedCrossRefGoogle Scholar
  40. 40.
    Michalek MT, Grant EP, Gramm C, et al: A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation. Nature 1993; 363: 552.PubMedCrossRefGoogle Scholar
  41. 41.
    Chiechanover A, Hod Y, Hershko A: A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem Biophys Res Commun 1978; 81: 1100.CrossRefGoogle Scholar
  42. 42.
    Hershko A, Leshinsky E, Ganoth D, et al: ATP-dependent degradation of ubiquitin-protein conjugates. Proc Natl Acad Sci USA 1984; 81: 1619.PubMedCrossRefGoogle Scholar
  43. 43.
    Hough R, Pratt G, Rechsteiner M: Purification of two highmolecularmass proteases from rabbit reticulocyte lysate. J Biol Chem 1987; 262: 8303.PubMedGoogle Scholar
  44. 44.
    Hershko A, Chiechaniver A, Heller H, et al: Proposed role of ATP in protein breakdown: conjugation of proteins with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci USA 1980; 77: 1783.PubMedCrossRefGoogle Scholar
  45. 45.
    Laub M, Jennissen HP: Synthesis and decay of calmodulinubiquitin conjugates in cell-free extracts of various rabbit tissues. Biochim Biophys Acta 1997; 1357: 173.PubMedCrossRefGoogle Scholar
  46. 46.
    Tiao G, Fagan JM, Samuels N, et al: Sepsis stimulates non-lysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J Clin Exp 1994; 94: 2255.Google Scholar
  47. 47.
    Tiao G, Fagan JM, Samuels N, et al: Sepsis increases proteasome dependent proteolysis and mRNA levels for the proteasome subunit RC2 in skeletal muscle. Surg Forum 1995; 46: 10.Google Scholar
  48. 48.
    Mansoor O, Beaufrere B, Boirie Y, et al: Increased mRNA levels for components of the lysosomal, Ca2+-activated, and ATP ubiquitin dependent proteolytic pathways in skeletal muscle from head trauma patients. Proc Nad Acad Sci USA 1996; 93: 2714.CrossRefGoogle Scholar
  49. 49.
    Cerra FB, Siegel JH, Colman B, Border J, McMenamy RH: Autocannibalism, a failure of exogenous nutritional support. Ann Surg 1980; 192: 570.PubMedCrossRefGoogle Scholar
  50. 50.
    Birkhahn R, Long C, Fitkin D, et al: Effects of major skeletal trauma on the whole body protein turnover in man measured by 1, 14C leucine. Surgery 1980; 88: 294.PubMedGoogle Scholar
  51. 51.
    Garber AJ: Glutamine metabolism in skeletal muscle. In: Mora J, Palacios R (eds) Glutamine: Metabolism, Enzymology and Regulation. San Diego, Academic, 1980; 259.Google Scholar
  52. 52.
    Lund P: Metabolism of glutamine, glutamate and aspartate. In: Waterlow JC, Stephen JML (eds) Nitrogen Metabolism in Man. London, Appl. Sci. 1981; 155.Google Scholar
  53. 53.
    Meister A: Metabolism of glutamine. Physiol Rev 1956; 36: 103.PubMedGoogle Scholar
  54. 54.
    Larsson J, Lennmarken C, Martensson J, et al: Nitrogen requirements in severely injured patients. Br J Surg 1990; 77: 413.PubMedCrossRefGoogle Scholar
  55. 55.
    Stehle P, Mertes N, Puchstein C, et al: Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1989; 1: 231–233.PubMedCrossRefGoogle Scholar
  56. 56.
    Mjaaland M, Unneberg K, Larsson J, et al: Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3-methylhistidine, and total amino acid efflux in patients receiving total parenteral nutrition. Ann Surg 1993; 217: 413.PubMedCrossRefGoogle Scholar
  57. 57.
    Bessey PQ, Watters JM, Aoki TT, Wilmore DW: Combined hormonal infusion stimulated the metabolic response to injury. Ann Surg 1984; 200: 264.PubMedCrossRefGoogle Scholar
  58. 58.
    Tessari P, Inchiostro S, Barazzoni R, et al: Hyperglucagonemia stimulates phenylalanine oxidation in humans. Diabetes 1996; 45: 463.PubMedCrossRefGoogle Scholar
  59. 59.
    Kayali AC, Young VR, Goodman MN: Sensitivity of myofibrillar proteins to glucocorticoid-induced muscle proteolysis. Am J Physiol 1987; 252: E621.PubMedGoogle Scholar
  60. 60.
    Darmann D, Matthews DE, Bier DM: Physiological hypercortisolemia increases proteolysis, glutamine and alanine production. Am J Physiol 1988; 255: E366.Google Scholar
  61. 61.
    Brillon DJ, Zheng B, Campbell RG, et al: Effect of Cortisol on energy expenditure and amino acid metabolism in humans. Am J Physiol 1995; 268: E501.PubMedGoogle Scholar
  62. 62.
    Price SR, England BK, Baily JL, et al: Acidosis and glucocorticoids concomitantly increase ubiquitin and proteasome subunitm RNAs in rat muscle. Am J Physiol 1994; 267: C955.PubMedGoogle Scholar
  63. 63.
    Choo JJ, Horan MA, little RA, et al: Anabolic effects of clanbuterol on skeletal muscle are mediated by β2-adrenoreceptor activation. Am J Physiol 1992; 92C: 135.Google Scholar
  64. 64.
    Biolo G, Memming RYD, Maggi SP, et al: Effects of hyperinsulinemia on muscle protein kinetics in severely burned patients. Clin Nutr 1994; 13: 23.CrossRefGoogle Scholar
  65. 65.
    Herndon DN, Nguyen TT, Wolfe RR, et al: Lipolysis in burned patients is stimulated by the β2-receptor for catecholamines. Arch Surg 1994; 129: 1301.PubMedCrossRefGoogle Scholar
  66. 66.
    Ader R, Felten DL, Cohen N: Psychoimmunology, 2nd ed. San Diego, Academic, 1991Google Scholar
  67. 67.
    Reichlin S: Neuroendocrine-immune interactions. N Engl J Med 1993; 329: 1246.PubMedCrossRefGoogle Scholar
  68. 68.
    Madden KS, Felten DL: Experimental basis for neural-immune interactions. Physiol Rev 1995; 75: 77.PubMedGoogle Scholar
  69. 69.
    Jeffries MK, Vance ML: Growth hormone and Cortisol secretion in patients with burn injury. J Burn Care Rehabil 1992; 13: 391.PubMedCrossRefGoogle Scholar
  70. 70.
    Jeevanandam M, Ramias L, Shamos RF, et al: Decreased growth hormone levels in the catabolic phase of severe injury. Surgery 1992; 111: 495.PubMedGoogle Scholar
  71. 71.
    Jeevanandam M, Holaday NJ, Peteresen SR: Adjuvant recombinant human growth hormone does not augment endogenous glucose production in total parenteral nutrition-fed multiple trauma patients. Metabolism 1996; 45: 450.PubMedCrossRefGoogle Scholar
  72. 72.
    Voerman HJ, Strack van Schijndel RJM, Groeneveld ABJ, et al: Effects of recombinant human growth hormone in patients with severe sepsis. Ann Surg 1992; 216: 648.PubMedCrossRefGoogle Scholar
  73. 73.
    Moshage H: Cytokines and the hepatic acute phase response. J Pathol 1997; 181: 257.PubMedCrossRefGoogle Scholar
  74. 74.
    Kushner I: The phenomenon of the acute phase response. Ann NY Acad Sci 1982; 389: 39.PubMedCrossRefGoogle Scholar
  75. 75.
    Baumann H, Gauldie J: The acute phase response. Immunol Today 1994; 15: 74.PubMedCrossRefGoogle Scholar
  76. 76.
    Koj A: Biological functions of acute-phase proteins. In: Gordon AH, Koj A (eds) The Acute Phase Response of Injury and Infection. Amsterdam, Elsevier, 1985; 145.Google Scholar
  77. 77.
    Pannen BHJ, Robotham JL: The acute-phase response. New Horiz 1995; 3: 183.PubMedGoogle Scholar
  78. 78.
    Kushner I: Regulation of the acute phase response by cytokines. Perspect Biol Med 1993; 36: 611.PubMedGoogle Scholar
  79. 79.
    Perlmutter DH, Dinarello CA, Punsal PI, et al: Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 1986; 78: 1349.PubMedCrossRefGoogle Scholar
  80. 80.
    Koj A, Rokita H, Kordula T, et al: Role of cytokines and growth factors in the induced synthesis of proteinase inhibitors belonging to acute phase proteins. Biomed Biochim Acta 1991; 50: 421.PubMedGoogle Scholar
  81. 81.
    Andus G, Geiger T, Hirano T, et al: Action of recombinant human interleukin 1β and tumor necrosis factor α on the mRNA induction of acute-phase proteins. Eur J Immunol 1988; 18: 739.PubMedCrossRefGoogle Scholar
  82. 82.
    Morrone G, Cortese R, Sorrentino V: Post-transcriptional control of negative acute phase genes by transforming growth factor β. EMBOJ 1989; 8: 3767.Google Scholar
  83. 83.
    Lang CH: Role of cytokines in glucose metabolism. In: Aggarwal BB, Puri RK (eds) Human Cytokines. Their Role in Disease and Therapy. Cambridge, Blackwell, 1995; 271.Google Scholar
  84. 84.
    Michie HR, Spriggs DR, Manogue KR, et al: Tumor necrosis factor and endotoxin induce similar metabolic responses in humans. Surgery 1988; 104: 280.PubMedGoogle Scholar
  85. 85.
    Zamir O, Hasselgren PO, O’Brien W, et al: Muscle protein breakdown during endotoxemia in rats and after treatment with interleukin-1 receptor antagonist (IL-lra). Ann Surg 1992; 16: 381.CrossRefGoogle Scholar
  86. 86.
    Tiao G, Fagan J, Roegner V, et al: Energy-ubiquitin-dependent muscle proteolysis during sepsis in rats is regulated by glucocorticoids. J Clin Invest 1996; 97: 339.PubMedCrossRefGoogle Scholar
  87. 87.
    Zamir O, O’Brien W, Thompson RC, et al: Reduced muscle protein breakdown in septic rats following treatment with interleukin-1 receptor antagonist. Int J Biochem 1994; 26: 943.PubMedCrossRefGoogle Scholar
  88. 88.
    Zamir O, Hasselgren PO, James H, et al: Effect of tumor necrosis factor or interleukin-1 on muscle amino acid uptake and the role of glucocorticoids. Surg Gynecol Obstet 1993; 177: 27.PubMedGoogle Scholar
  89. 89.
    Zamir O, Hasselgren PO, Higashiguchi T, et al: Tumor necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms. Mediat Inflamm 1992; 1: 247.CrossRefGoogle Scholar
  90. 90.
    Häussinger D, Roth E, Lang G, et al: Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 1993; 341: 1330.PubMedCrossRefGoogle Scholar
  91. 91.
    Häussinger D: Cellular hydratation: an important determinant of protein catabolism. In: Cynober L, Fürst P, Lawin P (eds) Pharmacological Nutrition. Immune Nutrition. Munich: W. Zuckschwerdt Verlag, 1995; 50.Google Scholar
  92. 92.
    HäussingerY D, Lang F, Häussinger D: Regulation of cell function by the cellular hydration state. Am J Physiol 1994; 267: E343.PubMedGoogle Scholar
  93. 93.
    Lang F, Häussinger D: Interaction of Cell Volume and Cell Function. Heidelberg, Springer, 1993Google Scholar
  94. 94.
    Häussinger D, Roth E, Lang F, et al: Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 1993; 341: 1330.PubMedCrossRefGoogle Scholar
  95. 95.
    Busch GL, Schreiber R, Dartsch PC, et al: Involvement of microtubules in the link between cell volume and pH of acidic cellular compartments in rat and human hepatocytes. Proc Natl Acad Sci USA 1994; 91: 9165.PubMedCrossRefGoogle Scholar
  96. 96.
    Chandra S, Chandra RK: Nutrition and the immune system. Proc Nutr Soc 1993; 341: 1330.Google Scholar
  97. 97.
    Irving TT: Effects of malnutrition and hyperalimentation on wound healing. Surg Gynecol Obstet 1978; 146: 33.Google Scholar
  98. 98.
    Streat SJ, Beddoe AH, Hill GL: Aggressive nutritional support does not prevent protein loss, despite fat gain in septic intensive care patients. J Trauma 1987; 27: 262.PubMedCrossRefGoogle Scholar
  99. 99.
    Bengmark S, Gianotti L: Nutritional support to prevent and treat multiple organ failure. World J Surg 1996; 20: 474.PubMedCrossRefGoogle Scholar
  100. 100.
    Guarnieri G, Toigo G, Situlin R, et al: Muscle-biopsy studies on protein metabolism in traumatized patients. In: Dietze G, Grunert T, Kleinberg A, Wolfram S (eds) Clinical Nutrition and Metabolic Research, Research Proceedings, 7th Congress Espen, Munich, Basel: Karger, 1986; 28.Google Scholar
  101. 101.
    Biolo G, Toigo G, Ciocchi B, et al: Metabolic response to injury and sepsisxhanges in protein metabolism. Nutrition 1997; 13: 52S.PubMedCrossRefGoogle Scholar
  102. 102.
    Michie HR: Metabolism of sepsis and multiple organ failure. World J Surg 1996; 20: 460.PubMedCrossRefGoogle Scholar
  103. 103.
    Rock KL, Gramm C, Rothstein L, et al: Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 1994; 78: 761.PubMedCrossRefGoogle Scholar
  104. 104.
    Tiao GM, Fagan J, Lieberman M, et al: Sepsis increases proteasome-dependent proteolysis and mRNA levels for the proteasome subunit RC3 in skeletal muscle. Surg Forum 1995; 46: 10.Google Scholar
  105. 105.
    Schow SR, Joly A: N-Acetyl-leucinyl-leucinyl-norleucinal inhibits lipopolysaccharide-induced NF-kappaB activation and prevents TNF and IL-6 synthesis in vivo. Cell Immunol 1997; 175: 199.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  • Matthias Majetschak
  • Christian Waydhas

There are no affiliations available

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