No oxygen delivery limitation in hepatic encephalopathy
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.
KeywordsBrain energy metabolism Cerebral blood flow Cerebral metabolic rate for oxygen Hepatic encephalopathy
- 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
- 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
- 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
- Krogh A (1919c) The supply of oxygen to the tissues and the regulation of the capillary circulation. J Physiol 52:458–474Google Scholar
- Roy CS, Sherrington CS (1890) On the regulation of the blood supply to the brain. J Physiol (London) 11(1–2):85–158Google Scholar