Rats exposed to high concentrations of carbon tetrachloride suffer rapid and extensive liver damage. Light microscopic examination of affected liver specimens shows fatty change and hepatocyte necrosis. These changes are the result of:

Question

Rats exposed to high concentrations of carbon tetrachloride suffer rapid and extensive liver damage.  Light microscopic examination of affected liver specimens shows fatty change and hepatocyte necrosis.  These changes are the result of:

Quizplus · Accepted Answer

Carbon tetrachloride (CCl₄) causes free radical injury. Like many other toxic substances, CCl₄ is oxidized by the P450 oxidase system in the liver. The result is the formation of the free radical CCl₃, which reacts with structural lipids of cell membranes. The result is lipid degradation and hydrogen peroxide (H₂O₂) formation. This process is called lipid peroxidation. The peroxides go on to form new radicals, continuing the vicious circle of lipid degradation. Carbon tetrachloride cell injury develops rapidly and leads to swelling of the endoplasmic reticulum, destruction of mitochondria, and increased permeability of cell membranes. These processes culminate in hepatocyte necrosis. (Choices A and B) Hypoperfusion and hypoxia lead to tissue ischemia and necrosis. Carbon tetrachloride does not affect tissue oxygenation. (Choice C) Abnormal signal transduction is a mechanism of oncogenesis, as occurs with mutations of the Ras proto-oncogene. This mutation increases cell sensitivity to mitogenic influences. (Choice E) Mitochondrial dysfunction occurs in CCl₄ intoxication as a result of free radical injury. Educational Objective: The P450 microsomal oxidase system plays an important role in detoxification. In carbon tetrachloride poisoning, however, it produces free radicals that start a vicious cycle of hepatic injury.

Rats Exposed to High Concentrations of Carbon Tetrachloride Suffer Rapid