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CHAPTER 23 The Alcohols 401

Alcohol may also impair visual acuity, with painless blurring and other substances that may protect against atherosclerosis. These
that occurs over several weeks of heavy alcohol consumption. observational studies are intriguing, but randomized clinical trials
Changes are usually bilateral and symmetric and may be followed examining the possible benefit of moderate alcohol consumption in
by optic nerve degeneration. Ingestion of ethanol substitutes such prevention of CHD have not been carried out.
as methanol (see Pharmacology of Other Alcohols) causes severe
visual disturbances. D. Blood
Alcohol indirectly affects hematopoiesis through metabolic and
C. Cardiovascular System nutritional effects and may also directly inhibit the proliferation
1. Cardiomyopathy and heart failure—Alcohol has complex of all cellular elements in bone marrow. The most common hema-
effects on the cardiovascular system. Heavy alcohol consumption tologic disorder seen in chronic drinkers is mild anemia resulting
of long duration is associated with a dilated cardiomyopathy with from alcohol-related folic acid deficiency. Iron deficiency anemia
ventricular hypertrophy and fibrosis. In animals and humans, may result from gastrointestinal bleeding. Alcohol has also been
alcohol causes cardiac membrane disruption, depressed function implicated as a cause of several hemolytic syndromes, some of
of mitochondria and sarcoplasmic reticulum, intracellular accu- which are associated with hyperlipidemia and severe liver disease.
mulation of phospholipids and fatty acids, and up-regulation of
voltage-gated calcium channels. There is evidence that patients E. Endocrine System and Electrolyte Balance
with alcohol-induced dilated cardiomyopathy do significantly Chronic alcohol use has important effects on the endocrine system
worse than patients with idiopathic dilated cardiomyopathy, and on fluid and electrolyte balance. Clinical reports of gyneco-
even though cessation of drinking is associated with a reduction mastia and testicular atrophy in alcoholics with or without cirrho-
in cardiac size and improved function. The poorer prognosis for sis suggest a derangement in steroid hormone balance.
patients who continue to drink appears to be due in part to inter- Individuals with chronic liver disease may have disorders of
ference by ethanol with the beneficial effects of β blockers and fluid and electrolyte balance, including ascites, edema, and effu-
angiotensin-converting enzyme (ACE) inhibitors. sions. Alterations of whole body potassium induced by vomiting
and diarrhea, as well as severe secondary aldosteronism, may
2. Arrhythmias—Heavy drinking—and especially “binge” contribute to muscle weakness and can be worsened by diuretic
drinking—are associated with both atrial and ventricular arrhyth- therapy. The metabolic derangements caused by metabolism of
mias. Patients undergoing alcohol withdrawal syndrome can large amounts of ethanol can result in hypoglycemia, as a result
develop severe arrhythmias that may reflect abnormalities of of impaired hepatic gluconeogenesis, and in ketosis, caused by
potassium or magnesium metabolism as well as enhanced release excessive lipolytic factors, especially increased cortisol and growth
of catecholamines. Seizures, syncope, and sudden death during hormone.
alcohol withdrawal may be due to these arrhythmias.
3. Hypertension—A link between heavier alcohol consump- F. Fetal Alcohol Syndrome
tion (more than three drinks per day) and hypertension has been Chronic maternal alcohol abuse during pregnancy is associated
firmly established in epidemiologic studies. Alcohol is estimated with teratogenic effects, and alcohol is a leading cause of mental
to be responsible for approximately 5% of cases of hypertension, retardation and congenital malformation. The abnormalities
independent of obesity, salt intake, coffee drinking, and cigarette that have been characterized as fetal alcohol syndrome include
smoking. A reduction in alcohol intake appears to be effective in (1) intrauterine growth retardation, (2) microcephaly, (3) poor
lowering blood pressure in hypertensive individuals who are also coordination, (4) underdevelopment of midfacial region (appear-
heavy drinkers; the hypertension seen in this population is also ing as a flattened face), and (5) minor joint anomalies. More severe
responsive to standard blood pressure medications. cases may include congenital heart defects and mental retardation.
Although the level of alcohol intake required to cause serious neu-
4. Coronary heart disease—Although the deleterious effects of rologic deficits appears quite high, the threshold for more subtle
excessive alcohol use on the cardiovascular system are well estab- neurologic deficits is uncertain.
lished, there is strong epidemiologic evidence that moderate alcohol The mechanisms that underlie ethanol’s teratogenic effects
consumption actually prevents coronary heart disease (CHD), isch- are unknown. Ethanol rapidly crosses the placenta and reaches
emic stroke, and peripheral arterial disease. This type of relationship concentrations in the fetus that are similar to those in maternal
between mortality and the dose of a drug is called a “J-shaped” blood. The fetal liver has little or no alcohol dehydrogenase activ-
relationship. Results of these clinical studies are supported by ity, so the fetus must rely on maternal and placental enzymes for
ethanol’s ability to raise serum levels of high-density lipoprotein elimination of alcohol.
(HDL) cholesterol (the form of cholesterol that appears to protect The neuropathologic abnormalities seen in humans and in
against atherosclerosis; see Chapter 35), by its ability to inhibit animal models of fetal alcohol syndrome indicate that ethanol
some of the inflammatory processes that underlie atherosclerosis triggers apoptotic neurodegeneration and also causes aberrant
while also increasing production of the endogenous anticoagulant neuronal and glial migration in the developing nervous system.
tissue plasminogen activator (t-PA, see Chapter 34), and by the In tissue culture systems, ethanol causes a striking reduction in
presence in alcoholic beverages (especially red wine) of antioxidants neurite outgrowth.