酒精增加肝脏的耗氧量、导致缺氧性肝损伤

Hypermetabolic State and Hypoxic Liver Damage

超代谢的概念解释酒精代谢耐受性，是从认识到酒精代谢的速率一般受限于线粒体重新氧化还原当量的速率，从而受限于肝脏耗氧量的速率。

这种关系在酒精脱氢酶(ADH)/Q(>2)比值高的情况下显得尤为重要，而且与观察表明ADH在某些条件下可以构成啮齿动物乙醇代谢的速率决定步骤的结果没有冲突。

长期喂食酒精的动物的肝脏，酒精代谢的增加被证明，消耗氧的速率更高。这种影响在调查人员之间存在差异，这取决于准备的肝脏类型。

甲状腺激素在高代谢状态的发展中起着允许的作用，而这些激素的循环水平的增加是不需要的。抗甲状腺药物可抑制体内代谢耐受和超代谢状态。虽然高代谢状态需要以腺苷三磷酸酶的形式增加ATP的利用，或者抑制ATP的合成，但这种作用的不同机制并不能定量解释氧消耗的增加。

在人类和动物中，长期暴露在乙醇的人类和动物，中断后，离开肝脏的血液中的氧张力明显降低。在某些情况下，肝泡3区低氧张力可达到临界缺氧水平，并可能导致细胞坏死。讨论了丙基硫氧嘧啶在酒精性肝炎中的作用。

　

Hypermetabolic State and Hypoxic Liver Damage

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In humans and animals chronically exposed to ethanol, but withdrawn, oxygen tensions in blood leaving the liver are significantly reduced.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.

 https://www.researchgate.net/publication/16866877_Hypermetabolic_State_and_Hypoxic_Liver_Damage