Hepatocellular Damage Examples

Microvesicular fatty change • Tetracycline, salicylates, yellow phosphorus, ethanol

Macrovesicular fatty change • Ethanol, methotrexate, amiodarone

Centrilobular necrosis • Bromobenzene, CCl4 , acetaminophen, halothane, rifampin

Diffuse or massive necrosis • Halothane, isoniazid, acetaminophen, methyldopa, trinitrotoluene, Amanita phalloides (mushroom) toxin

Hepatitis, acute and chronic • Methyldopa, isoniazid, nitrofurantoin, phenytoin, oxyphenisatin

Fibrosis-cirrhosis • Ethanol, methotrexate, amiodarone, most drugs that cause chronic hepatitis

Granuloma formation • Sulfonamides, methyldopa, quinidine, phenylbutazone, hydralazine, allopurinol

Cholestasis (with or without hepatocellular injury) • Chlorpromazine, anabolic steroids, erythromycin estolate, oral contraceptives, organic arsenicals

Among the agents listed in Table 18-8 , hepatic injury is considered predictable from overdoses of acetaminophen (also called phenacetin or paracetamol) and exposure to Amanita

phalloides toxin, carbon tetrachloride, and, to a certain extent, alcohol. However, individual genetic differences in the hepatic metabolism of xenobiotics through activating and

detoxification pathways play a major role in individual susceptibility to "predictable" hepatotoxins. Many other xenobiotics, such as sulfonamides, a-methyldopa, and allopurinol, cause

idiosyncratic reactions. Reye syndrome, a potentially fatal syndrome of mitochondrial dysfunction in liver, brain, and elsewhere, occurs predominantly in children who are given

acetylsalicylic acid (aspirin) for the relief of virus-induced fever. This disease, which features extensive accumulation of fat droplets within hepatocytes (microvesicular steatosis), is

exceedingly rare. A causal relationship with use of salicylates was never established, but a national campaign in the 1970s and 1980s warning against the use of aspirin in children with

febrile illness might have served to break the Reye syndrome epidemic.

Drug-induced liver disease is usually followed by recovery upon removal of the drug. Exposure to a toxin or therapeutic agent should always be included in the differential diagnosis of

liver disease.

Figure 18-23Alcoholic liver disease. The interrelationships among hepatic steatosis, hepatitis, and cirrhosis are shown, along with a depiction of key morphologic features at the

morphologic level.

Figure 18-24Alcoholic liver disease: macrovesicular steatosis, involving most regions of the hepatic lobule. The intracytoplasmic fat is seen as clear vacuoles. Some early fibrosis (stained

blue) is present (Masson trichrome).

Figure 18-25Alcoholic hepatitis. A, The cluster of inflammatory cells marks the site of a necrotic hepatocyte. A Mallory body is present in a second hepatocyte (arrow). B, Eosinophilic

Mallory bodies are seen in hepatocytes, which are surrounded by fibrous tissue (H&E).

Figure 18-26Alcoholic cirrhosis. A, The characteristic diffuse nodularity of the surface reflects the interplay between nodular regeneration and scarring. The greenish tint of some nodules

is due to bile stasis. A hepatocellular carcinoma is present as a budding mass at the lower edge of the right lobe (lower left of figure). B, The microscopic view shows nodules of varying

sizes entrapped in blue-staining fibrous tissue. The liver capsule is at the top (Masson trichrome).

TABLE 18-9-- Classification of Iron Overload

Date: 2016-04-22; view: 640