Skip to main content
SpringerLink
Log in

Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice

  • Original Articles
  • Published:
Surgery Today Aims and scope Submit manuscript

Abstract

The effect of the hepatic energy status on the development of posttraumatic jaundice (PTJ) was studied to clarify the mechanism of PTJ. Fifty-four patients with severe torso injury who were expected to develop PTJ on admission with an average Injury Severity Score of 27 were selected for this study. They were retrospectively divided into three groups according to their maximum bilirubin concentration by day 10: group H, 12 patients with marked elevation of serum bilirubin (>8 g/dl); group L, 23 with mild bilirubinemia (2–8 g/dl); and group N, 19 with no bilirubinemia (<2 g/dl). Group H patients, in whom trauma-related shock was severe and prolonged, developed severe hyperbilirubinemia, and their arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state and is closely correlated to its energy production, was significantly lower throughout the first week. In contrast, the AKBR increased to an above normal level, indicating enhanced energy production in groups N and L. The serum direct/total bilirubin was also higher in group H. The abnormal hepatic energy metabolism is considered to have reduced the excretion of conjugated bilirubin from the hepatocytes into the bile canaliculi, which is a process that has to proceed against the bilirubin concentration gradient. The subsequent diffusion of the accumulated water-soluble conjugated bilirubin in hepatocytes into the blood is thus considered to be one of the causes of PTJ.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Champion HR, Jones RT, Trump BF, Decker R, Wilson S, Stega M, Nolan J, Cowley RA, Gill W (1976) Post-traumatic hepatic dysfunction as a major etiology in post-traumatic jaundice. J Trauma 16:650–657

    Google Scholar 

  2. Champion HR, Jones RT, Trump BF, Decker R, Wilson S, Miginski M, Gill W (1976) A clinicopathologic study of hepatic dysfunction following shock. Surg Gynecol Obstet 142:657–663

    Google Scholar 

  3. Sarfeh J, Balint JA (1978) The clinical significance of hyperbilirubinemia following trauma. J Trauma 18:58–62

    Google Scholar 

  4. Van Thiel DH, Lester R (1975) Postoperative jaundice. Mechanism, diagnosis and treatment. Surg Clin North Am 55:409–418

    Google Scholar 

  5. Boekhorst T, Urlus M, Doesburg W, Yap SH, Goris RJA (1988) Etiologic factors of jaundice in severely ill patients. Hepatology 7:111–117

    Google Scholar 

  6. Evans C, Evans M, Pollock AV (1974) The incidence and causes of postoperative jaundice. A prospective study. Br J Anaesth 46:520–525

    Google Scholar 

  7. Schmidt M, Hefti ML, Gattiker R, Kistler HJ, Senning A (1965) Benign postoperative intrahepatic cholestasis. N Engl J Med 272:545–550

    Google Scholar 

  8. Kantrowitz PA, Jones WA, Greenberger NJ, Isselbacher KJ (1967) Severe postoperative hyperbilirubinemia simulating obstructive jaundice. N Engl J Med 276:591–598

    Google Scholar 

  9. Iwata S, Tanaka A, Ozawa K (1992) Alterations in the proton ATPase activity of rat liver mitochondria after hemorrhagic shock. J Lab Clin Med 120:420–427

    Google Scholar 

  10. Yamamoto M, Ozawa K, Tobe T (1981) Roles of high blood glucose concentration during hemorrhagic shock in alloxan diabetic rats. Circ Shock 8:49–57

    Google Scholar 

  11. Shimahara Y, Ozawa K, Ida T, Ukikusa M, Tobe T (1981) Four stages of mitochondrial deterioration in hemorrhagic shock. Res Exp Med 179:23–33

    Google Scholar 

  12. Crawford JM, Hauser SC, Gollan JL (1988) Formation, hepatic metabolism, and transport of bile pigments. A status report. Semin Liver Dis 8:105–118

    Google Scholar 

  13. Arias IM (1976) Bilirubin metabolism. In: Bockus HL (ed) Gastroenterology, vol. 3. Saunders, Philadelphia, pp 171–181

    Google Scholar 

  14. Ozawa K (1994) Living related donor liver transplantation. Karger, Basel, pp 12–29

    Google Scholar 

  15. Ozawa K (1992) Liver surgery approached through the mitochondria. Medical Tribune, Tokyo, pp 57–116

    Google Scholar 

  16. Kitai T, Tanaka A, Terasaki M, Okamoto R, Ozawa K, Morikawa S, Inobushi T (1991) Energy metabolism of the liver in brain dead dogs assessed by 31P-NMR spectroscopy and arterial ketone body ratio. Life Sci 49:511–518

    Google Scholar 

  17. Ozawa K, Chance B, Tanaka A, Iwata S, Kitai T, Ikai I (1992) Linear correlation between acetoacetate/β-hydroxybutyrate in arterial blood and oxidized flavoprotein/reduced pyridinenucleotide in freeze-trapped human liver tissue. Biochim Biophys Acta 1138:350–352

    Google Scholar 

  18. Nakatani T, Yokoo N, Kasai T, Kobayashi K (1987) Dissociation of the blood ketone body ratio in hemorrhagic shock as a parameter of hepatic functional reserve (in Japanese with English abstract). Nippon Gaisho Kenkyu Kaishi (J Jpn Assoc Surg Trauma) 1(2):10–15

    Google Scholar 

  19. The abbreviated injury scale, 1985 Revision. American Association for Automotive Medicine

  20. Uno S, Ito S, Kurono M, Yamaoka Y, Kamiyama Y, Ozawa K (1987) A simple and sensitive assay for blood ketone bodies using highly purified 3-hydroxybutyrate dehydrogenase. Clin Chim Acta 168:253–255

    Google Scholar 

  21. Ozawa K (1983) Biological significance of mitochondrial redox potential in shock and multiple organ failure. Redox theory. In: Lefer AM, Schumer W (eds) Molecular and cellular aspects of shock and trauma. Alan R Liss, New York, pp 39–66

    Google Scholar 

  22. Ozawa K, Aoyama H, Yasuda K, Shimahara Y, Nakatani T, Tanaka J, Yamamoto M, Kamiyama Y, Tobe T (1983) Metabolic abnormalities associated with postoperative organ failure: A redox theory. Arch Surg 118:1245–1251

    Google Scholar 

  23. Ukikusa M, Ozawa K, Shimahara Y, Asano M, Nakatani T, Tobe T (1981) Changes in blood ketone body ratio. Their significance after major hepatic resection. Arch Surg 116:781–785

    Google Scholar 

  24. Yamamoto M, Tanaka J, Ozawa K, Tobe T (1980) Significance of acetoacetate/β-hydroxybutyrate ratio in arterial blood as an indicator of the severity of hemorrhagic shock. J Surg Res 28:124–131

    Google Scholar 

  25. Wallenstein S, Zucker CL, Fleiss J (1981) Some statistical methods useful in circulation research. Circ Shock 8:503–517

    Google Scholar 

  26. Fry DE, Pearlstein L, Fulton RL, Polk HC Jr (1980) Multiple system organ failure. The role of uncontrolled infection. Arch Surg 115:136–140

    Google Scholar 

  27. Goris RJA, Boekhorst TPA, Nuytinck JKS, Gimbrere JSF (1985) Multiple-organ failure. Generalized autodestructive inflammation? Arch Surg 120:1109–1115

    Google Scholar 

  28. Leon Schiff (1975) Jaundice: A clinical approach. In: Schiff L, Schiff ER (eds) diseases of the liver, 5th edn. Lippincott, Philadelphia, pp 397–392

    Google Scholar 

  29. Tiribelli C, Ostrow JD (1990) New concepts in bilirubin chemistry, transport and metabolism. Hepatology 11:303–313

    Google Scholar 

  30. Hofmann AF. Current concepts of biliary secretion (1989) Dig Dis Sci 34:16S-20S

    Google Scholar 

  31. Erlinger S (1982) Secretion of bile. In: Schiff L, Schiff ER (eds) Diseases of the liver, 5th edn. Lippincott, Philadelphia, pp 93–118

    Google Scholar 

  32. Arias IM, Johnson L, Wolfson S (1961) Biliary excretion of injected conjugated and unconjugated bilirubin by normal and Gunn rats. Am J Physiol 200:1091–1094

    Google Scholar 

  33. Jansen PLM, Peters WHM, Meijer DKF (1987) Hepatobiliary excretion of organic anions in double-mutant rats with a combination of defective canalicular transport and uridine 5′-diphosphate-glucuronyl transferase deficiency. Gastroenterology 93:1094–1103

    Google Scholar 

  34. Kitamura T, Jansen P, Hardenbrook C, Kamimoto U, Gatmaintan Z, Arias IM (1990) Defective ATP-dependent bile canalicular transport of organic anions in mutant (TR−) rats with conjugated hyperbilirubinemia. Proc Natl Acad Sci USA 87:3557–3561

    Google Scholar 

  35. Singhal SS, Sharma R, Gupta S, Ahmad H, Zimniak P, Radominska A, Lester R, Awasthi YA (1991) The anionic conjugates of bilirubin and bile acids stimulate ATP hydrolysis by S-(dinitrophenyl) glutathione ATPase of human erythrocyte. FEBS Lett 281:255–25

    Google Scholar 

  36. Lehninger AL (1977) Catabolism and the generation of phosphate-bond energy. In: Lehninger AL (ed) Biochemistry, 2nd edn. Worth, New York, pp 361–616

    Google Scholar 

  37. Pettit FH, Pelley JW, Reed LJ (1975) Regulation of pyruvate dehydrogenase kinase and phosphatase by acetyl-CoA/CoA and NADH/NAD ratio. Biochem Biophys Res Commun 65:575–582

    Google Scholar 

  38. Yamaoka Y, Shimahara Y, Nakatani T, Mori K, Kobayashi N, Maki A, Nitta N, Yamamoto S, Ozawa K (1988) Clinical role of blood ketone body ratio as an indicator evaluating hepatic tolerance for portal triad cross-clamping in cirrhotic liver resection. Surg Res Commun 3:87–93

    Google Scholar 

  39. Nakatani T, Shimahara Y, Mori K, Kobayashi N, Yamaoka Y, Kobayashi K, Ozawa K (1989) Analysis of hemodynamics and blood gas in relation to blood ketone body ratio in partially hepatectomized patients. Eur Surg Res 21:205–212

    Google Scholar 

  40. Yamamoto Y, Ozawa K, Okamoto R, Kiuchi T, Maki A, Lin H, Mori K, Shimahara Y, Kumada K, Yamaoka Y (1990) Prognostic implications of postoperative suppression of arterial ketone body ratio: Time factor involved in the suppression of hepatic mitochondrial oxidation-reduction state. Surgery 107:289–294

    Google Scholar 

  41. Kiuchi T, Shimahara Y, Wakashiro S, Tokunaga, Y, Ozaki N, Takayasu T, Mori K, Kobayashi N, Yamaoka Y, Ozawa K (1990) Reduced arterial Ketone body ratio during laparotomy: An evaluation of operative stress through the changes in hepatic mitochondrial redox potential. J Lab Clin Med 115:433–440

    Google Scholar 

  42. Kiuchi T, Ozawa K, Yamamoto Y, Takayasu T, Maki A, Shimahara Y, Mori K, Kobayashi N, Yamaoka Y, Kumada K (1990) Changes in arterial ketone body ratio in the phase immediately after hepatectomy; Prognostic implications. Arch Surg 125:655–659

    Google Scholar 

  43. Yamaoka Y, Taki Y, Gubernatis G, Nakatani T, Okamoto R, Yamamoto Y, Ishikawa Y, Ringe B, Bundendahl H, Oellerich M, Kobayashi K, Ozawa K, Pichlmayr R (1990) Evaluation of the liver graft before procurement: Significance of arterial ketone body ratio in brain-dead patients. Transplant Int 3:78–81

    Google Scholar 

  44. Nakatani T, Ishikawa Y, Kobayashi K, Ozawa K (1991) Hepatic mitochondrial redox state in hypotensive brain-dead patients and an effect of dopamine administration. Intensive Care Med 17:103–107

    Google Scholar 

  45. Williamson DH, Lund P, Krebs HA (1967) The redox state of free nicotineamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem J 103:514–527

    Google Scholar 

  46. Ikai I, Shimahara Y, Wakashiro S, Ozaki N, Tokunaga Y, Tanaka A, Morimoto T, Ozawa K (1988) Influence of hemorrhagic shock on hepatic energy metabolism in carbon tetrachloride induced cirrhotic rats. Circ Shock 26:365–374

    Google Scholar 

  47. Ohtoshi M, Jikko A, Asano M, Uchida K, Ozawa K, Tobe T (1984) Ketogenesis during sepsis in relation to hepatic energy metabolism. Res Exp Med 184:209–219

    Google Scholar 

  48. Taki Y, Gubernatis G, Yamaoka Y, Oellerich M, Yamamoto Y, Ringe B, Okamoto R, Bunzendahl H, Beneking M, Burdelski M, Bornscheuer A, Ozawa K, Pichlmayr R (1990) Significance of arterial ketone body ratio measurement in human liver transplatation. Transplantation 49:535–539

    Google Scholar 

  49. Ozaki N, Gubernatis G, Ringe B, Oellerich M, Washida M, Yamaoka Y, Ozawa K, Pichlmayr R (1991) Arterial ketone body ratio as an indicator for viability of donor livers. Transplantation Proc 23:2487–2489

    Google Scholar 

  50. Ozaki N, Ringe B, Bunzendahl H, Taki Y, Gubernatis G, Oellerich M, Kuse ER, Kiuchi T, Yamauchi K, Takada Y, Yamaguchi T, Ozawa K, Pichlmayr R (1991) Ketone body ratio as an indicator of early graft survival in clinical liver transplantation. Clin Transplantation 5:48–54

    Google Scholar 

  51. Asonuma K, Takaya S, Selby R, Okamoto R, Yamamoto Y, Tokoyama T, Todo S, Ozawa K, Starzl TE (1991) The clinical significance of the arterial ketone body ratio as an early indicator of graft viability in human liver transplantation. Transplantation 51:164–171

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Trauma and Critical Care Center, Teikyo University School of Medicine, 11-1 Kaga, 2-chome, Itabashi-ku, 173, Tokyo, Japan

    Toshio Nakatani, Yukio Endoh & Kunio Kobayashi

Authors
  1. Toshio Nakatani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukio Endoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kunio Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakatani, T., Endoh, Y. & Kobayashi, K. Significance of the hepatic mitochondrial redox state in the development of posttraumatic jaundice. Surg Today 25, 490–497 (1995). https://doi.org/10.1007/BF00311304

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00311304

Key Words

Search

Navigation