Metabolic Brain Disease

, Volume 25, Issue 1, pp 57–63 | Cite as

No oxygen delivery limitation in hepatic encephalopathy

  • Albert Gjedde
  • Susanne Keiding
  • Hendrik Vilstrup
  • Peter Iversen
Original Paper

Abstract

Hepatic encephalopathy is a condition of reduced brain functioning in which both blood flow and brain energy metabolism declined. It is not known whether blood flow or metabolism is the primary limiting factor of brain function in this condition. We used calculations of mitochondrial oxygen tension to choose between cause and effect in three groups of volunteers, including healthy control subjects (HC), patients with cirrhosis of the liver without hepatic encephalopathy (CL), and patients with cirrhosis with acute hepatic encephalopathy. Compared to HC subjects, blood flow and energy metabolism had declined in all gray matter regions of the brain in patients with HE but not significantly in patients with CL. Analysis of flow-metabolism coupling indicated that blood flow declined in HE as a consequence of reduced brain energy metabolism implied by the calculation of increased mitochondrial oxygen tensions that patients with HE were unable to utilize. We ascribe the inability to use the delivered oxygen of patients with HE to a specific inhibition associated with oxidative metabolism in mitochondria.

Keywords

Brain energy metabolism Cerebral blood flow Cerebral metabolic rate for oxygen Hepatic encephalopathy 

References

  1. Bohr C (1909) Über die spezifische Tätigkeit der Lungen bei der respiratorischen Gasaufnahme und ihr Verhalten zu der durch die Alveolarwand statt findenden Gasdiffusion. Skandinavisches Archiv Physiologie 22:221–280Google Scholar
  2. Chen JL, Wei L, Bereczki D, Hans FJ, Otsuka T, Acuff V, Richardson G, Patlak C, Fenstermacher J (1994) Virtually unaltered permeability-surface area products imply little capillary recruitment in brain with hypoxia. Microcirculation 1(1):35–47CrossRefPubMedGoogle Scholar
  3. Gjedde A, Marrett S, Vafaee M (2002) Oxidative and nonoxidative metabolism of excited neurons and astrocytes. J Cereb Blood Flow Metab 22(1):1–14CrossRefPubMedGoogle Scholar
  4. Gjedde A, Johannsen P, Cold GE, Ostergaard L (2005) Cerebral metabolic response to low blood flow: possible role of cytochrome oxidase inhibition. J Cereb Blood Flow Metab 25(9):1183–1196CrossRefPubMedGoogle Scholar
  5. Hudetz AG (1997) Regulation of oxygen supply in the cerebral circulation. Adv Exp Med Biol 428:513–520PubMedGoogle Scholar
  6. Iversen P, Sørensen M, Bak LK, Waagepetersen HS, Vafaee MS, Borghammer P, Mouridsen K, Jensen SB, Vilstrup H, Schousboe A, Ott P, Gjedde A, Keiding S (2008) Low cerebral oxygen consumption and blood flow in patients with cirrhosis and an acute episode of hepatic encephalopathy. Gastroenterology 136(3):863–871CrossRefPubMedGoogle Scholar
  7. Krogh A (1919a) The rate of diffusion of gases through animal tissues, with some remarks on the coefficient of invasion. J Physiol 52:392–408Google Scholar
  8. Krogh A (1919b) The number and distribution of capillaries in muscles with calculation of the oxygen pressure head necessary for supplying the tissue. J Physiol 52:409–415PubMedGoogle Scholar
  9. Krogh A (1919c) The supply of oxygen to the tissues and the regulation of the capillary circulation. J Physiol 52:458–474Google Scholar
  10. Kuschinsky W, Paulson OB (1992) Capillary circulation in the brain. Cerebrovasc Brain Metab Rev 4(3):261–286PubMedGoogle Scholar
  11. Ohta S, Meyer E, Thompson CJ, Gjedde A (1992) Oxygen consumption of the living human brain measured after a single inhalation of positron emitting oxygen. J Cereb Blood Flow Metab 12(2):179–192PubMedGoogle Scholar
  12. Ohta S, Meyer E, Fujita H, Reutens DC, Evans A, Gjedde A (1996) Cerebral [15O]water clearance in humans determined by PET: I. Theory and normal values. J Cereb Blood Flow Metab 16(5):765–780CrossRefPubMedGoogle Scholar
  13. Paulson OB, Hasselbalch SG, Rostrup E, Knudsen GM, Pelligrino D (2010) Cerebral blood flow response to functional activation. J Cereb Blood Flow Metab 30(1):2–14CrossRefPubMedGoogle Scholar
  14. Roy CS, Sherrington CS (1890) On the regulation of the blood supply to the brain. J Physiol (London) 11(1–2):85–158Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Albert Gjedde
    • 1
    • 2
    • 3
  • Susanne Keiding
    • 1
    • 4
  • Hendrik Vilstrup
    • 4
  • Peter Iversen
    • 1
  1. 1.Pathophysiology and Experimental Tomography CenterAarhus Hospital, Aarhus University HospitalsAarhusDenmark
  2. 2.Department of Neuroscience and PharmacologyUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of Neurology and NeurosurgeryMcGill UniversityMontrealCanada
  4. 4.Department of Hepatology VAarhus Hospital, Aarhus University HospitalsAarhusDenmark

Personalised recommendations