Skip to main content
SpringerLink
Log in

The Brain and Liver

  • Chapter
  • First Online:
The Liver in Systemic Diseases

  • 1317 Accesses

Abstract

The brain integrates numerous sources of information and stimuli from both inside and outside the body and responds to them both voluntarily and involuntarily. To maintain this function, the brain consumes a great deal of energy and oxygen through a large blood supply. The supply of blood, energy, and substances used by the neurons in the brain are strictly regulated by a principal framework of the brain, the neurovascular unit, which includes the blood-brain barrier. The information transduction of the brain nervous system is executed through the electrical conduction of membrane action potentials and chemical transmission at the synapses. Metabolic disorders, such as hypoglycemia and hyperammonemia due to liver failure, perturb the energy supply and the information transduction of the brain nervous system and cause a range of brain disorders that are represented by hepatic encephalopathy (HE). Although the precise mechanisms of HE have not been fully elucidated, noninvasive methods of examination that have been recently developed, including high-quality magnetic resonance spectroscopy and imaging, have made it possible to evaluate the metabolic changes that occur in the brain of cirrhotic patients and then reveal the accumulation of toxic substances prior to overt manifestation of HE.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hall JE. Guyton and hall textbook of medical physiology. 12th ed. New York: Saunders; 2011.

    Google Scholar 

  2. Paulson OB, Strandgaard S, Edvinsson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev. 1990;2(2):161–92.

    CAS  PubMed  Google Scholar 

  3. Bruyn GW, Klawans HL, Vinken PJ, Vinken PJ, Klawans HL. Handbook of clinical neurology: vascular diseases v. 53: vascular diseases, vol 53 (Handbook of clinical neurology-revised Edition). 1st ed. Amsterdam: Elsevier Science Ltd; 1989.

    Google Scholar 

  4. Hammer GD, McPhee SJ. Pathophysiology of disease: an introduction to clinical medicine. 7th ed. New York: McGraw-Hill; 2014.

    Google Scholar 

  5. Schacter DL, Gilbert DT, Wegner DM. Psychology. 2nd ed. New York: Worth Publishers; 2011.

    Google Scholar 

  6. Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, McNamara JO, White LE. Neuroscience. 4th ed. Sunderland: Sinauer Associates; 2007.

    Google Scholar 

  7. Santello M, Volterra A. Synaptic modulation by astrocytes via Ca2+-dependent glutamate release. Neuroscience. 2009;158(1):253–9.

    Article  CAS  PubMed  Google Scholar 

  8. Kettenmann H, Ransom BR. Neuroglia. 3rd ed. New York: Oxford University Press; 2012.

    Book  Google Scholar 

  9. Zlokovic BV. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008;57(2):178–201.

    Article  CAS  PubMed  Google Scholar 

  10. Guo S, Lo EH. Dysfunctional cell-cell signaling in the neurovascular unit as a paradigm for central nervous system disease. Stroke. 2009;40(3 Suppl):S4–7.

    Article  PubMed  Google Scholar 

  11. Takahashi S, Abe T. Roles of astrocytes in the regulation of CBF in response to neuronal activation and metabolic demand. Cereb Blood Flow Metab Online J. 2005;17:150–5.

    Google Scholar 

  12. Pellerin L, Magistretti PJ. Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A. 1994;91(22):10625–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Valeur N, Clemmensen P, Saunamäki K, Grande P, DANAMI-2 investigators. The prognostic value of pre-discharge exercise testing after myocardial infarction treated with either primary PCI or fibrinolysis: a DANAMI-2 sub-study. Eur Heart J. 2005;26(2):119–27.

    Article  PubMed  Google Scholar 

  14. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on demand. Science. 1999;283(5401):496–7.

    Article  CAS  PubMed  Google Scholar 

  15. Takahashi S, Abe T, Izawa Y, Iizumi T, Suzuki N. Roles of blood-brain barrier in neurovascular unit and cellular metabolic compartment. Cereb Blood Flow Metab Online J. 2013;24(2):75–82.

    Google Scholar 

  16. Takahashi S, Izawa Y, Suzuki N. Astroglial pentose phosphate pathway rates in response to high-glucose environments. ASN Neuro. 2012;4(2):71–88.

    Google Scholar 

  17. Guzmán M, Blázquez C. Is there an astrocyte-neuron ketone body shuttle? Trends Endocrinol Metab. 2001;12(4):169–73.

    Article  PubMed  Google Scholar 

  18. Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000;130(4S Suppl):1007S–15.

    CAS  PubMed  Google Scholar 

  19. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol. 2002;213:1–47.

    Article  CAS  PubMed  Google Scholar 

  20. López-Corcuera B, Geerlings A, Aragón C. Glycine neurotransmitter transporters: an update. Mol Membr Biol. 2001;18(1):13–20.

    Article  PubMed  Google Scholar 

  21. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K. Hepatic encephalopathy-definition, nomenclature, diagnosis and quantification; final report of the working party at the 11th World Congress of Gastroenterology, Vienna, 1998. Hepatology. 2002;35(3):716–21.

    Article  PubMed  Google Scholar 

  22. Kato A, Tanaka H, Kawaguchi T, et al. Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: a preliminary, prospective, open-label study. Hepatol Res. 2013;43(5):452–8.

    Article  CAS  PubMed  Google Scholar 

  23. Kaneta H, Kato A, Suzuki K. Clinical manifestation of subclinical hepatic encephalopathy in patients with non-alcoholic cirrhosis. Hepatol Jpn. 1994;35:167–71.

    Google Scholar 

  24. Groeneweg M, Quero JC, De Bruijin I, et al. Subclinical hepatic encephalopathy impairs daily functioning. Hepatology. 1998;28(1):45–9.

    Article  CAS  PubMed  Google Scholar 

  25. Schomerous H, Hamster W, Blunck H, et al. Latent portosystemic encephalopathy. I. Nature of cerebral functional defects and their effect on fitness to drive. Did Dis Sci. 1981;26(7):622–30.

    Article  Google Scholar 

  26. Das A, Dhiman RK, Saraswat VA, et al. Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J Gastroenterol Hepatol. 2001;16(5):531–5.

    Article  CAS  PubMed  Google Scholar 

  27. Amodio P, Montagnese S, Gatta A, et al. Characteristics of minimal hepatic encephalopathy. Metab Brain Dis. 2004;19(3–4):253–67.

    Article  PubMed  Google Scholar 

  28. Kato A, Kato M, Ishii H, et al. Development of quantitative neuropsychological tests for diagnosis of subclinical hepatic encephalopathy in liver cirrhosis patients and establishment of diagnostic criteria- multicenter collaborative study in Japanese. Hepatol Res. 2004;30(2):71–8.

    Article  PubMed  Google Scholar 

  29. Kooka Y, Sawara K, Endo R, et al. Brain metabolism in minimal hepatic encephalopathy assessed by 3.0-Tesla magnetic resonance spectroscopy. Hepatol Res. 2015;46:269–76.

    Google Scholar 

  30. Phelpes ME, Hoffman EJ, Raybaund C. Factors which affect cerebral uptake and retention of 13NH3. Stroke. 1977;8(6):694–702.

    Article  Google Scholar 

  31. Tranah TH, Vijay GK, Ryan JM, Shawcross DL. Systemic inflammation and ammonia in hepatic encephalopathy. Metab Brain Dis. 2013;28(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  32. Schenker S. Hepatic encephalopathy. In: Butterworth RF, Pomier Layrargues G, editors. The present and the future. Hepatic encephalopathy, experimental biology and medicine, vol. 22. Clifton: Humana Press; 1989. p. 3–24.

    Chapter  Google Scholar 

  33. Hindfelt B, Plum F, Duffy TE. Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest. 1977;59(3):386–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bessaman SP, Bessaman AN. The cerebral and peripheral uptake of ammonia in liver disease with an hypothesis for the mechanism of hepatic coma. J Clin Invest. 1955;34(4):622–8.

    Article  Google Scholar 

  35. Butterworth RF, Vaquero J. In: Aris I, Alter H, Boyer J, Cohen D, Feusto N, Shafritz D, Wollkoff A, editors. Hepatic encephalopathy: the liver: biology and pathology. 5th ed. Hoboken: Wiley; 2009.

    Google Scholar 

  36. Lai JC, Cooper AJ. Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem. 1986;47(5):1376–86.

    Article  CAS  PubMed  Google Scholar 

  37. Lockwood AH, Yap EW, Rhoades HM, Wong WH. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. J Cereb Blood Flow Metab. 1991;11(2):331–6.

    Article  CAS  PubMed  Google Scholar 

  38. Lux HD. Ammonium and chloride extrusion. Hyperpolarizing synaptic inhibition in spinal motoneurons. Science. 1971;173(3996):555–7.

    Article  CAS  PubMed  Google Scholar 

  39. Raabe WA. Neurophysiology of ammonia intoxication. In: Butterworth RF, Pomier Layrargues G, editors. Hepatic encephalopathy, experimental biology and medicine, vol. 22. Clifton: Humana Press; 1989. p. 49–77.

    Chapter  Google Scholar 

  40. Norenberg MD. A light and electron microscopic study of experimental portal-systemic (ammonia) encephalopathy. Progression and reversal of the disorder. Lab Investig. 1977;36(6):618–27.

    CAS  PubMed  Google Scholar 

  41. Gregorios JB, Mozes LW, Norenberg LO, Norenberg MD. Morphologic effects of ammonia on primary astrocyte cultures. I. Light microscopic studies. J Neuropathol Exp Neurol. 1985;44(4):397–403.

    Article  CAS  PubMed  Google Scholar 

  42. Swain M, Butterworth RF, Blei AT. Ammonia and related amino acids in the pathogenesis of brain edema in acute ischemic liver failure in rats. Hepatology. 1992;15(3):449–53.

    Article  CAS  PubMed  Google Scholar 

  43. O’Keefe SJ, Abraham R, El-Zayadi A, Marshall W, Davis M, Williams R. Increased plasma tyrosine concentrations in patients with cirrhosis and fulminant hepatic failure associated with increased plasma tyrosine flux and reduced hepatic oxidation capacity. Gastroenterology. 1981;81(6):1017–24.

    PubMed  Google Scholar 

  44. Schafer DF, Jones EA. Hepatic encephalopathy and the gamma-aminobutyric-acid neurotransmitter system. Lancet. 1982;1(8262):18–20.

    Article  CAS  PubMed  Google Scholar 

  45. Fischer JE, Baldessarini RJ. False neurotransmitters and hepatic failure. Lancet. 1971;2(7715):75–80.

    Article  CAS  PubMed  Google Scholar 

  46. Ahboucha S, Butterworth RF. The neurosteroid system: implication in the pathophysiology of hepatic encephalopathy. Neurochem Int. 2008;52:575–87.

    Article  CAS  PubMed  Google Scholar 

  47. Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encephalopathy. N Engl J Med. 2010;362(12):1071–81.

    Article  CAS  PubMed  Google Scholar 

  48. Katayama K, Saito M, Sawara K, et al. Effect of zinc on liver cirrhosis with hyperammonemia: a preliminary randomized, placebo-controlled double-blind trial. Nutrition. 2014;30(11–12):1409–14.

    Article  CAS  PubMed  Google Scholar 

  49. Takuma Y, Nouso K, Makino K, et al. Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther. 2010;32(9):1080–90.

    Article  CAS  PubMed  Google Scholar 

  50. Barbaro G, Di Lorenzo G, Soldini M, et al. Flumazenil for hepatic coma in patients with liver cirrhosis: an Italian multicentre double-blind, placebo-controlled, crossover study. Eur J Emerg Med. 1998;5:213–8.

    Article  CAS  PubMed  Google Scholar 

  51. Sharma P, Sharma BC, Puri V, Sarin SK. An open-label randomized controlled trial of lactulose and probiotics in the treatment of minimal hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2008;20(6):506–11.

    Article  CAS  PubMed  Google Scholar 

  52. Malaguarnera PG, Elvira R, et al. Effects of L-carnitine in patients with hepatic encephalopathy. World J Gastoenterol. 2005;11:7197–202.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hepatology, Department of Internal Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan

    Yasuhiro Takikawa, Hidekatsu Kuroda & Kei Sawara

Authors
  1. Yasuhiro Takikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hidekatsu Kuroda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kei Sawara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiro Takikawa .

Editor information

Editors and Affiliations

  1. Dept. Gastroenterology & Rheumatogy, Fukushima Med. Univ. School of Med., Fukushima, Fukushima, Japan

    Hiromasa Ohira

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this chapter

Cite this chapter

Takikawa, Y., Kuroda, H., Sawara, K. (2016). The Brain and Liver. In: Ohira, H. (eds) The Liver in Systemic Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55790-6_4

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55790-6_4

  • Published:

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55789-0

  • Online ISBN: 978-4-431-55790-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation