Discover the Mechanisms of Liver Injury

Types of Liver Injury and Their Mechanisms

• Toxicants can induce various toxic effects on different organelles in liver cells through biochemical reactions.
• The mechanisms of liver injury include lipid peroxidation, covalent binding, protein synthesis inhibition, biliary production/flow disturbance, immunologic reaction, and calcium homeostasis perturbation.
• Fatty liver is a liver that contains more than 5% lipid by weight, induced by ethanol, methotrexate, tetracycline, or other toxicants.
• Liver necrosis involves the death of hepatocytes and can be focal or massive, induced by carbon tetrachloride, chloroform, phosphorus, acetaminophen, isoniazid, iproniazid, and other toxicants.
• Cholestasis is a less common type of liver damage, usually acute, induced by ethinyl estradiol, anabolic and contraceptive steroids, chlorpromazine, erythromycin lactobionate, and other toxicants.
• Cirrhosis is characterized by the presence of septae of collagen throughout most of the liver, induced by several chemical carcinogens, long-term administration of CC74, and chronic ingestion of alcoholic beverages.
• The mechanism of cirrhosis is not fully understood, but ethanol may damage mitochondria and increase local production of reactive oxygen species, leading to steatosis, necrosis, and cirrhosis.
• Ethanol-induced cirrhosis in animals requires a combination of ethanol and diets deficient in choline, proteins, methionine, vitamin B12, and folic acid.
• Fatty liver can occur due to inhibition of lipoprotein synthesis, reduced conjugation of triglyceride with lipoproteins, and loss of potassium from hepatocytes.
• Early morphologic changes in liver necrosis include cytoplasmic edema, dilatation of endoplasmic reticulum, and disaggregation of polysomes.
• Late changes in liver necrosis are progressive swelling of mitochondria and cytoplasm, dissolution of organelles and nucleus, and rupture of plasma membrane.
• Carbon tetrachloride acts primarily through its reactive metabolite, the trichloromethyl radical CC13, which covalently binds with proteins and unsaturated lipids and induces lipid peroxidation, leading to a disturbance of liver cell Ca homeostasis and cell death.