Organ System Lesion Mechanism

Liver Fatty change Toxicity

Acute hepatitis

Alcoholic cirrhosis

Nervous system Wernicke syndrome Thiamine deficiency

Korsakoff syndrome Toxicity and thiamine deficiency

Cerebellar degeneration Nutritional deficiency

Peripheral neuropathy Thiamine deficiency

Cardiovascular system Cardiomyopathy Toxicity

Hypertension Vasopressor

Gastrointestinal tract Gastritis Toxicity

Pancreatitis Toxicity

Skeletal muscle Rhabdomyolysis Toxicity

Reproductive system Testicular atrophy ?

Spontaneous abortion ?

Fetal alcohol syndrome Growth retardation Toxicity

Mental retardation

Birth defects

Data from Rubin E: Alcohol abuse. In Craighead JE (ed): Pathology of Environmental and Occupational Disease. St. Louis, Mosby-Year Book, 1996, p. 249; and Lewis DD, Woods SE:

Fetal alcohol syndrome. Am Fam Physician 50:1025, 1994.

central nervous system depressant, chronic ethanol use can cause a wide range of systemic effects ( Table 9-5 ). Some of these chronic effects can be attributed to specific vitamin

deficiencies; for example, damage to the peripheral and central nervous systems is related to thiamine deficiency, whereas

other systemic effects result from direct toxicity. The effects of ethanol on various organ systems are discussed next.

Liver.

Ethanol can cause fatty change, acute alcoholic hepatitis, and cirrhosis. Fatty change is an acute, reversible manifestation of ethanol ingestion. In chronic alcoholism, fat accumulation can

cause massive enlargement of the liver. The biochemical mechanisms responsible for fat accumulation in hepatocytes are the following:

• Catabolism of fat by peripheral tissues is increased, and there is increased delivery of free fatty acids to the liver.

• Metabolism of ethanol in the cytosol and of its derivative, acetaldehyde, in the mitochondria converts the oxidized form of nicotinamide adenine dinucleotide (NAD+ ) to the

reduced form (NADH); an excess of NADH over NAD stimulates lipid biosynthesis.

• Oxidation of fatty acids by mitochondria is decreased.

• Acetaldehyde forms adducts with tubulin and impairs function of microtubules, resulting in decreased transport of lipoproteins from the liver.

Acute alcoholic hepatitis is another potentially reversible form of liver injury ( Chapter 18 ). Although fatty change is asymptomatic except for liver enlargement, alcoholic hepatitis can

produce fever, liver tenderness, and jaundice. On histologic examination, there are focal areas of hepatocyte necrosis and cell injury manifest by fat accumulation and alcoholic hyalin, or

Mallory bodies. Neutrophils accumulate around foci of necrosis ( Fig. 9-6 ). Ethanol and its metabolites are directly toxic to hepatocytes; this toxicity is believed to be mediated by

glutathione depletion, mitochondrial injury, altered metabolism of methionine, and cytokine release from Kupffer cells.[16] Hepatocellular necrosis, as well as fibrosis, begins around the

central vein, suggesting that hypoxia may contribute to this injury. With chronic ethanol use, 10% to 15% of alcoholics develop irreversible liver damage, or alcoholic cirrhosis. This is

characterized by a hard, shrunken liver with formation of micronodules of regenerating hepatocytes surrounded by dense bands of collagen ( Fig. 9-7 ). Alcoholic cirrhosis is a serious,

potentially fatal disease accompanied by weakness, muscle wasting, ascites, gastrointestinal hemorrhage, and coma. Perisinusoidal fibrosis occurs initially, with

Figure 9-6Acute alcoholic hepatitis. The liver cells show cytoplasmic accumulation of fat and hyalin (arrow). A scattered inflammatory infiltrate is present. (MEDCOM © 1976.)

Figure 9-7Micronodular cirrhosis is a late complication of chronic alcoholism. The liver architecture is distorted by regenerating nodules of hepatocytes surrounded by dense bands of

fibrous tissue that stain blue (Masson trichrome stain). (Courtesy of Dr. Steve Kroft, Department of Pathology, Southwestern Medical School, Dallas, TX.)

TABLE 9-6-- Common Drugs of Abuse

Date: 2016-04-22; view: 818