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Hypermetabolic State and Hypoxic Liver Damage

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Recent Developments in Alcoholism

Abstract

The concept of a hypermetabolic state to explain metabolic tolerance to ethanol grew from the recognition that the rate of alcohol metabolism is, in general, limited by the rate at which mitochondria can reoxidize reducing equivalents and thus by the rate at which oxygen can be consumed by the liver. This relationship appears to be most important in conditions in which the alcohol dehydrogenase (ADH)/Q(>2 ratio is high and is not in conflict with observations suggesting that ADH can, under certain conditions, constitute a rate-determining step for ethanol metabolism in rodents.

Liver preparations from animals fed alcohol chronically, in which an increase in ethanol metabolism is shown, consume oxygen at higher rates. This effect, concerning which there is discrepancy among investigators, depends on the type of preparation. Thyroid hormones play a permissive role in the development of the hypermetabolic state, while increased circulating levels of these hormones are not required. Antithyroid drugs inhibit both metabolic tolerance in vivo and the hypermetabolic state. While the hypermetabolic state requires an increased ATP utilization in the form of an adenosine triphosphatase, or an inhibition of ATP synthesis, the different mechanisms proposed for such an effect do not quantitatively account for the increases in oxygen consumption. In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced. In some situations, low oxygen tensions in zone 3 of the hepatic acinus can reach critical hypoxic levels and may lead to cell necrosis. Studies in which the effectiveness of propylthiouracil is tested in human alcoholic hepatitis are discussed.

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Authors and Affiliations

  1. Departments of Pharmacology and Medicine, University of Toronto, M5S 1A8, Toronto, Ontario, Canada

    Yedy Israel & Hector Orrego

  2. Addiction Research Foundation, M5S 2S1, Toronto, Ontario, Canada

    Yedy Israel & Hector Orrego

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  1. Yedy Israel
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  1. Albert Einstein College of Medicine, Bronx, New York, USA

    Marc Galanter

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Israel, Y., Orrego, H. (1984). Hypermetabolic State and Hypoxic Liver Damage. In: Galanter, M., et al. Recent Developments in Alcoholism. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4661-6_7

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  • DOI: https://doi.org/10.1007/978-1-4684-4661-6_7

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