skin tumors

adverse effects of alcohol abuse

alcohol can cause marked physical and psychological damage. our purpose here is to describe the lesions directly associated with the abuse of alcohol.
fifty percent-of adults in the western world drink alcohol, and about 5% to 10% have chronic alcoholism. it is estimated that there are more than 10 million chronic alcoholics in the united states and that alcohol consumption is responsible for more than 100,000 deaths annually. almost 50% of these deaths result from accidents caused by drunken driving and alcohol-related homicides and suicides, and about 25"/" are a consequence of cirrhosis of the liver.

metabolism of ethanol

after consumption, ethanol is absorbed unaltered in the stomach and small intestine. it is then distributed to all the tissues and fluids of the body in direct proportion to the blood level. less than 10% is excreted unchanged in the urine. sweat. and breath. the amount exhaled is proportional to the blood level and forms the basis of the breath test used by law enforcement agencies. a concentration
of 80mg/dl in the blood constitutes the legal definition of drunk driving in most states. the rate of metabolism affects the blood alcohol level. most of the alcohol in the blood is biotransformed to
acetaldehyde in the liver by three enzyme systems consisting
of alcohol dehydrogenase, cytochrome p-450 isoenzymes, and catalase . catalase activity, which utilizes hydrogen peroxide as substrate,is of minor importance. because it metabolizes no more than 5% of ethanol in the liver. acetaldehyde produced by alcohol
metabolism through these systems is converted to acetate by acetaldehyde dehydrogenase, which is then utilized in the mitochondrial respiratory chain. the main enzyme system involved in alcohol metabolism is alcohol dehydrogenase, located in the cytosol of hepatocytes. at high blood alcohol levels, the microsomal ethanol-oxidizing system participates in the metabolism. this system involves cytochrome p-450 enzymes, located in the smooth er. induction of
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p-450 enzymes by alcohol explains the increased susceptibility
of alcoholics to other compounds metabolized by
the same enzyme system, which include drugs (acetaminophen,
cocaine),anesthetics, carcinogens and industrial solvents. note, however, that when alcohol is present in the blood at high concentrations, it competes with other cytochrome p-450 enzymes substrates and may delay the catabolism of other drugs, thus potentiating their effects.

several toxic effects result from ethanol metabolism. we mention
only the most important of these.

1- alcohol oxidation by alcohol dehydrogenase causes a decrease in nicotinamide adenine dinucleotide (nad) and an increase in nadh (the reduced form of nad ). nad* is required for fatty acid oxidation in the liver. its deficiency is a main cause of accumulation of fat in the liver of alcoholics.
2- nad* is also required for the conversion of lactate into pyruvate, and the increase in the nadh/nad* ratio in alcoholics causes metabolic acidosis resulting from lactic acid accumulation.

3-metabolism of ethanol in the liver by cytochrome p-450 isoenzymes produces reactive oxygen species and causes lipid peroxidation of cell membranes. nevertheless, the precise mechanisms that account for alcohol-induced cellular injury have not been well defined.

4-alcohol may cause the release of endotoxin (lipopolysaccharide)a, product of gram-negative bacteria from the intestinal flora. endotoxin stimulates the release of tumor necrosis factor (tnf) and other cytokines from circulating macrophages and from kupffer cells in the liver, causing cell injury.

acetaldehyde has many toxic effects and may be responsible for some of the acute effects of alcohol. the efficiency of alcohol metabolism varies between populations, depending on the composition of acetaldehyde dehydrogenase isozymes, and of

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mutations that decrease enzyme activity.

the adverse effects of ethanol can be categorized into its acute effects and the consequences of chronic alcoholism.


acute alcoholism

acute alcoholism exerts its effects mainly on the cns, but it may induce hepatic and gastric changes that are reversible in the absence of continued alcohol consumption.

1-even with moderate intake of alcohol, multiple fat dropinglets accumulate in the cytoplasm of hepatocytes(fatty changes and hepatic steatosis)
2-in the stomach there are gastritis and ulceration.
3-in the cns first alcohol is a depressant for cerebral cortical function then there are stimulation and disordered cortical, motor and intellectual behavior. at progressively higher blood levels, cortical neurons and then lower medullary centers are depressed including those that regulate respiration.respiratory arrest may follow.

chronic alcoholism

chronic alcoholism is responsible for morphologic alterations, primarily in the liver and stomach, but they may occur in virtually all organs and tissues chronic alcoholics suffer significant morbidity and have a shortened life span, related principally to damage to the liver, gi tract, cns, cardiovascular system, and pancreas.

1-the liver is the main site of chronic injury. in addition to fatty change, mentioned above chronic alcoholism causes alcoholic hepatitis and cirrhosis, cirrhosis is associated with portal hypertension and an increased risk for the development of hepatocellular carcinoma

2-in the gi tract, chronic alcoholism can cause massive bleeding from gastritis, gastric ulcer, or esophageal varices (associated with

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cirrhosis), which may prove fatal.

3- thiamine deficiency is common in chronic alcoholic patients the principal lesions resulting from this deficiency are peripheral neuropathies and the wernicke-korsakoff syndrome (cerebral atrophy cerebellar degeneration, and optic neuropathy) may also occur.

4- alcohol has diverse effects on the cardio vascuiar system. injury to the myocardium may produce dilated congestive cardiomyopathy (alcoholic cardiomyopathy),
moderate amounts of alcohol (one drink per day) have been
reported to increase serum levels of high-density lipoproteins (hdl) and inhibit platelet aggregation, thus protecting against coronary heart disease. however, heavy consumption, with attendant liver injury, results in decreased levels of hdl, increasing the likelihood of coronary heart disease chronic alcoholismis also associated with an increased incidence of
hypertension.

5- excess alcohol intake increases the risk of acute and chronic pancreatitis.

6- the use of ethanol during pregnancy-reportedly as little as one drink per day-can cause fetal alcohol syndrome.it consists of microcephaly, growth retardation and facial abnormalities in the newborn and reduction in mental functions in older children. it is difficult to establish the amount of alcohol consumption that can cause fetal alcohol syndrome, but consumption during the first trimester of pregnancy is particularly harmful.

7-chronic alcohol consumption is associated with an increased incidence of cancer of the oral cavity, esophagus, iiver, and, possibly, breast in females. the mechanisms of the carcinogenic effect are uncertain.

8- ethanol is a substantial source of energy (empty calories). chronic alcoholism leads to malnutrition and vitamin b defeciency

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adverse effects of therapeutic drugs

aspirin( acetylsalicylic acid) overdose may result from accidental ingestion of a large number of 325mg tablets by young children in adults, overdose is frequently suicidal. the major untoward consequences are metabolic, with few morphologic changes. at first, respiratory alkalosis develops, followed by a metabolic acidosis that often proves fatal before anatomic changes can appear. ingestion of as iittle as 2 to 4gm by children or 10 to 30gm by adults may be fatal, but survival has been reported after doses five times larger.
chronic aspirin toxicity (salicylism) may develop in persons who take 3gm or more daily (the dose required to treat chronic inflammatory conditions). chronic salicylism is manifested by headache, dizziness, ringing in the ears (tinnitus), difficulty in hearing, mental confusion, drowsiness, nausea, vomiting, and diarrhea. the cns changes may progress to convulsions and coma. the morphologic consequences of chronic salicylism are varied. most often, there is an acute erosive gastritis , which may produce overt or covert gi bleeding and lead to gastric ulceration. a bleeding tendency may appear concurrently with chronic toxicity, because aspirin acetylates platelet cyclooxygenase and blocks the
ability to make thromboxane a2, an activator of platelet aggregation. petechial hemorrhages may appear in the skin and internal viscera, and bleeding from gastric ulcerations may be exaggerated.
proprietary analgesic mixtures of aspirin and phenacetin or its active metabolite, acetaminophen, when taken over several years, can cause tubulointerstitial nephritis with renal papillary necrosis, referred to as analgesic nephropathy









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