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The mechanism of ethanol induced hepatotoxicity in man - Essay Example

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Excessive alcohol (ethanol) consumption induces pathological changes in the liver which include alcoholic fatty liver, alcoholic hepatitis, and alcohol-related cirrhosis (Ismail 2006). Fatty liver is characterized by marked increase in the fat cells in the liver. In alcoholic…
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The mechanism of ethanol induced hepatotoxicity in man
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Alcohol damages liver as a dose-dependent hepatotoxin (Maddrey 2004). The damage is mainly due to the by-products of metabolism. After absorbed from the gastrointestinal tract, alcohol undergoes oxidation in the liver. The first step in the oxidation is conversion of ethanol to acetaldehyde and this is catalyzed by alcohol dehydrogenase. During this process, NADH (NAD, nicotinamide adenine dinucleotide) is released. The acetaldehyde is further oxidized to acetic acid which then enters the citric acid cycle and metabolized to carbondioxide and water.

NADH is used up in the conversion of pyruvic acid to lactic acid, in the synthesis of lipids and in the electron transport chain (Paton 2005). Most of the damage to cells caused by ethanol is due to acetaldehyde and NADH. Acetaldehyde causes damage due to immune response and increased NADH causes altered NADH/NAD ratio leading to increased oxygen consumption and hypermetabolic state (Tome 2004). During the initial stages of excessive alcohol consumption, fat deposition occurs in the liver. When fat deposition occurs without any evidence of cell inflammation, it is usually reversible and benign (Maddrey 2004).

However, gradually cell inflammation occurs resulting in liver necrosis and fibrosis. Acute fatty liver is caused by increased uptake of plasma-free fattyacids which are released secondary to enhanced blood flow in the liver, activation of phosphatidate phosphohydrolase and hypermobilization of adipose-tissue fat (Badawy 1980). The increase in hepatic blood flow is secondary to the direct stimulatory effect of alcohol on the adrenal and pituitary axis (Ismail 2006). Chronic fatty liver occurs due to chronic ingestion of alcohol which inhibits fatty acid oxidation in the liver.

There is also release of very low-density lipoprotein into the blood. As consumption of alcohol continues and increases, hypoxia ensues and there is shift in lipid metabolism leading to decreased energy stores.

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