PRINCIPLES OF TOXICOLOGY - Biology East Borneo

5.2 TYPES OF LIVER INJURY 123to produce hepatic venoocclusive disease, including many of natural origin such as pyrrolizidinealkaloids in herbal teas. Oral contraceptives and some anticancer drugs have also been associated withthis effect.Peliosis hepatis is another vascular lesion characterized by the presence of large, blood-filledcavities. It is unclear why these cavities form, but there is reason to suspect that it may be due to aweakening of sinusoidal supporting membranes. Use of anabolic steroids has been associated with thiseffect. Although patients with peliosis hepatis are usually without symptoms, the cavities occasionallyrupture causing bleeding into the abdominal cavity.CirrhosisChronic liver injury often results in the accumulation of collagen fibers within the liver, leading tofibrosis. Fibrotic tissue accumulates with repeated hepatic insult, making it difficult for the liver toreplace damaged cells and still maintain normal hepatic architecture. Fibrous tissue begins to formwalls separating cells. Distortions in hepatic microcirculation cause cells to become hypoxic and die,leading to more fibrotic scar tissue. Ultimately, the organization of the liver is reduced to nodules ofregenerating hepatocytes surrounded by walls of fibrous tissue. This condition is called cirrhosis.Hepatic cirrhosis is irreversible and carries with it substantial medical risks. Blood flow through theliver becomes obstructed, leading to portal hypertension. To relieve this pressure, blood is divertedpast the liver through various shunts not well suited for this purpose. It is common for vessels associatedwith these shunts to rupture, leading to internal hemorrhage. Even without hemorrhagic episodes, theliver may continue to decline until hepatic failure occurs.The ability of chronic ethanol ingestion to produce cirrhosis is widely appreciated. Occupationalexposures to carbon tetrachloride, trinitrotoluene, tetrachloroethane, and dimethylnitrosamine havealso been implicated as causing cirrhosis, as well as the medical use of arsenicals and methotrexate.Some drugs (e.g., methyldopa, nitrofurantoin, isoniazid, diclofenac) produce an idiosyncratic reactionresembling viral hepatitis. This condition, termed chronic active hepatitis, can also lead to cirrhosis ifthe drug is not withdrawn.TumorsMany chemicals are capable of producing tumors in the liver, particularly in laboratory rodents. Infact, in cancer rodent bioassays for carcinogenicity, the liver is the most common site of tumorigenicity.Hepatic tumors may be benign or malignant. Conceptually, the distinction between them is that benigntumors are well circumscribed and do not metastasize (i.e., do not invade other tissues). Malignanttumors, on the other hand, are poorly circumscribed and are highly invasive (see Chapter 13 foradditional discussion on benign and malignant tumors). Benign tumors, despite their name, are capableof producing morbidity and mortality. However, they are easier to manage and have a much betterprognosis than malignant tumors.Tumors are also classified by the tissue of origin, that is, whether they arise from epithelial ormesenchymal tissue, and by the specific cell type from which they originate. The nomenclature fornaming tumors is complex, and the reader is referred elsewhere for a complete discussion of the topic.Basically, malignant tumors arising from epithelial tissue are termed carcinomas, while malignanttumors of mesenchymal origin are sarcomas. Thus, malignant tumors derived from hepatocytes, whichare of epithelial origin, are termed hepatocellular carcinomas. Malignant tumors from bile duct cells,also of epithelial origin, are termed cholangiocarcinomas (the prefix cholangio- refers to the bile ducts).Cells of the vascular lining are of mesenchymal origin. Consequently, a malignant tumor in the liverarising from these cells may be called hemangiosarcoma. Benign tumors are also named on the basisof tissue of origin and their appearance. For example, benign tumors of epithelial origin with gland,or glandlike structures are called adenomas, and in the liver these can occur among hepatocytes or bileduct cells. Benign tumors of fibrotic cell origin are termed fibromas, and those in the bile ducts arecalled cholangiofibromas.