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Chronic Alcoholism

Ethanolum

For medical students2 min readUpdated 2026-10-10

Chronic alcoholism is the most common form of substance dependence, driven by an overwhelming pathological craving for alcoholic beverages. The condition is characterized by the development of persistent physical and psychological dependence, withdrawal syndrome upon cessation, profound personality deterioration, and severe somatic disorders.

MetabolismApproximately 90% of ingested ethanol undergoes enzymatic oxidation in the liver.

ToxicityThe primary damaging and mutagenic agent is not alcohol itself, but its active metabolite—acetaldehyde.

Elimination rateThe oxidation of pure ethanol is extremely slow: only 5–10 mL per hour.

GeneticsGenetic factors play a major role: the risk of developing dependence in children of individuals with alcoholism reaches 50%.

Pharmacokinetics and Routes of Ethanol Elimination

Ethyl alcohol (Ethanolum) has a high bioavailability. Following ingestion, it is rapidly absorbed from the stomach and small intestine into the systemic circulation. Due to its physicochemical properties, ethanol readily crosses cell membranes and penetrates the intracellular space of all body tissues.

Elimination of ethanol from the body occurs via two main pathways:

Excretion in unchanged form: This accounts for only 5% to 10% of the absorbed substance. Alcohol is excreted via urine, feces, sweat, exhaled breath, and, in nursing mothers, breast milk.
Biochemical oxidation: This is the primary elimination pathway, accounting for roughly 90% of ethanol metabolism. The process occurs predominantly in the liver. Notably, the rate of this process is strictly limited to just 5–10 mL per hour (calculated as pure alcohol). The end products of this oxidation are harmless water and carbon dioxide.

Biochemistry of Oxidation and Acetaldehyde Toxicity

Ethanol metabolism in the liver is a two-step enzymatic cascade:

In the first step, alcohol dehydrogenase (ADH) transforms ethyl alcohol into acetaldehyde.
In the second step, aldehyde dehydrogenase (ALDH), working in conjunction with Krebs cycle enzymes, breaks down acetaldehyde into water and carbon dioxide.

The core toxicokinetic problem is that the intermediate metabolite, acetaldehyde, is an extremely toxic compound. It circulates systemically, easily crosses cell membranes, and causes widespread cellular damage. The toxicity of alcohol itself is largely driven by the destructive effects of accumulating acetaldehyde.

Epidemiology and Risk Factors for Dependence

Chronic alcoholism follows distinct epidemiological patterns. The peak age for the onset of dependence is 20–29 years. Men are affected about five times more frequently than women. However, female alcoholism has unique features: it tends to involve solitary drinking and a more rapid progression of symptoms (higher progradient nature). Adolescent statistics are also concerning, with a prevalence of approximately 10–11 cases per 100,000 population.

Pathology development is promoted by a cluster of risk factors:

Consumption pattern: Systematic drinking (intoxication occurring at least once a week) and concurrent use of other psychotropic substances, including nicotine.
Socio-demographic: Male sex, young age, lack of a family.
Social: Economic, moral, and ideological deprivation within society.
Physiological: Innate hypersensitivity to alcohol.
Genetic: Family history of alcoholism. Heredity plays a massive role, with the risk of dependence reaching 50% in children of affected individuals.

Fetal Alcohol Syndrome (FAS)

Alcohol consumption during pregnancy poses a severe hazard. Repeated intake of large doses of alcohol by a pregnant individual causes severe fetal intoxication, resulting in fetal alcohol syndrome (FAS).

Clinical manifestations of FAS include a broad spectrum of morphofunctional abnormalities:

Cranial defects: Microcephaly (reduced head size) or megalocephaly.
Dysplasias: Pronounced structural defects of the teeth and auricles.
Internal organ malformations: Congenital anomalies of the heart, kidneys, and gastrointestinal tract.
Musculoskeletal pathology: Various myopathies and arthropathies.
Neuropsychiatric impairments: Persistent intellectual disability, ranging up to severe idiocy.

Mutagenic Mechanism and General Pathogenesis Links

Ethanol alone does not exhibit marked genotoxicity. Its toxic metabolite, acetaldehyde, serves as the primary mutagenic agent. Strong evidence comes from studies of individuals with a low-activity isoform of hepatic aldehyde dehydrogenase (ALDH2). In these individuals, even moderate alcohol consumption leads to an increased frequency of genetic material exchanges between chromosomes in lymphocytes compared to people with normal enzyme activity.

Despite psychoactive substances having diverse chemical structures, the key pathogenic links in dependence formation are universal. These include the development of an irresistible pathological craving for repeated substance use and the establishment of persistent psychological dependence.

Mnemonic

To remember metabolic enzymes: ADH (Alcohol Dehydrogenase) turns alcohol into poison, while ALDH (Aldehyde Dehydrogenase) detoxifies that poison.

Frequently asked questions

Which neurotransmitter systems of the brain are involved in physical dependence on ethanol?

Several brain neurotransmitter systems participate in physical dependence and withdrawal syndrome during ethanol use.

Catecholaminergic/dopaminergic system — cessation leads to an accumulation of dopamine and other biogenic amines in brain tissue; catecholamine excess, particularly in reward pathways, is a key driver of withdrawal.
Opioidergic system — chronic substance use leads to a downregulation of opioid receptors; prolonged hypercatecholaminemia is typically accompanied by reduced opioidergic activity.
Glutamatergic system — chronic alcoholism increases the activity of the excitatory glutamatergic system.
GABAergic system — chronic alcoholism suppresses the inhibitory GABAergic system.
Serotonergic and cholinergic systems — under conditions of physical dependence and prolonged hypercatecholaminemia, their activity generally decreases.

What are the pathophysiological mechanisms of alcohol withdrawal syndrome at the cellular level?

At the cellular level, withdrawal syndrome is driven by altered physicochemical properties of cell membranes and neurotransmitter imbalance.

Membrane adaptation — regular alcohol intake increases cell membrane viscosity due to the accumulation of excess cholesterol and higher fatty acids; during withdrawal, receptors 'float up' to the plasma membrane surface.
Neurotransmitter accumulation — catecholamine synthesis rates remain high by inertia while utilization drops, leading to excessive dopamine accumulation in brain tissue.
Neurotransmitter imbalance — clinical manifestations are driven by adaptive system shifts disrupting the balance between glutamate and GABA.

What triggers withdrawal syndrome in alcoholism?

Withdrawal syndrome occurs upon cessation of alcohol intake against the background of established physical dependence on the substance.

Why is the toxic effect of alcohol more pronounced in some individuals?

This is related to genetic variations, specifically a low-activity isoform of hepatic aldehyde dehydrogenase (ALDH2), which leads to the accumulation of toxic acetaldehyde in the body.

What is the natural oxidation rate of alcohol in the body?

Calculated as pure alcohol, the oxidation rate is only 5–10 mL per hour, strictly limiting the body's capacity to eliminate the toxin.

Go deeper

Mechanisms of psychological and physical dependence on psychoactive substances.
Pathogenesis of personality deterioration in chronic intoxication.
Somatic and neuropsychiatric disorders in alcoholism.
Influence of nicotine and other psychotropic substances on the progression rate of alcoholism.