Alcohol (ethanol) is a drug, and health professionals should know something of its physiological and pathological

effects and its handling by the body. It is a small, water soluble molecule that is rela vely slowly absorbed from the
stomach, more rapidly absorbed from the small intes ne, and freely distributed throughout the body. Alcoholic
drinks are a major source of energy—for example, six pints of beer contain about 500 kcal and half a litre of whisky
contains 1650 kcal. The daily energy requirement for a moderately ac ve man is 3000 kcal and for a woman 2200
kcal.

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Absorp on

Rate of absorp on of alcohol depends on several factors. It is quickest, for example, when alcohol is drunk on an
empty stomach and the concentra on of alcohol is 20-30%. Thus, sherry, with an alcohol concentra on of about 20%
increases the levels of alcohol in blood more rapidly than beer (3-8%), while spirits (40%) delay gastric emptying and
inhibit absorp on. Drinks aerated with carbon dioxide—for example, whisky and soda, and champagne—get into the
system quicker. Food, and par cularly carbohydrate, retards absorp on: blood concentra ons may not reach a
quarter of those achieved on an empty stomach. The pleasurable effects of alcohol are best achieved with a meal or
when alcohol is drunk diluted, in the case of spirits.spirits.

Figure 1

Rate of absorp on of alcohol (arrows) is affected by concentra on of alcohol

Alcohol is distributed throughout the water in the body, so that most ssues—such as the heart, brain, and
muscles—are exposed to the same concentra on of alcohol as the blood. The excep on is the liver, where exposure
is greater because blood is received direct from the stomach and small bowel via the portal vein. Alcohol diffuses
rather slowly, except into organs with a rich blood supply such as the brain and lungs.lungs.
Figure 2

Most ssues are exposed to the same alcohol concentra on as in the blood

Other factors

Very li le alcohol enters fat because of fat's poor solubility. Blood and ssue concentra ons are therefore higher in
women, who have more subcutaneous fat and a smaller blood volume, than in men, even when the amount of
alcohol consumed is adjusted for body weight. Women also may have lower levels of alcohol dehydrogenases in the
stomach than men, so that less alcohol is metabolised before absorp on. Alcohol enters the fetus readily through the
placenta and is eliminated by maternal metabolism.

Blood alcohol concentra on varies according to sex, size and body build, phase of the menstrual cycle (it is highest
premenstrually and at ovula on), previous exposure to alcohol, type of drink, whether alcohol is taken with food or
drugs, such as cime dine (which inhibits gastric alcohol dehydrogenase) and an histamines, phenothiazines, and
metoclopramide (which enhance gastric emptying, thus increasing absorp on).absorp on).
Figure 3

Metabolism of ethanol

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Metabolism of alcohol

More than 90% of alcohol is eliminated by the liver; 2-5% is excreted unchanged in urine, sweat, or breath. The first
step in metabolism is oxida on by alcohol dehydrogenases, of which at least four isoenzymes exist, to acetaldehyde
in the presence of cofactors. Acetaldehyde is a highly reac ve and toxic substance, and in healthy people it is
oxidised rapidly by aldehyde dehydrogenases to harmless acetate.

This ar cle is adapted from the 4th edi on of the ABC of Alcohol, which will be available in February

Several isoenzymes of aldehyde dehyrdrogenase exist, one of which is missing in about 50% of Japanese people and
possibly other south Asian people (but rarely in white people). Unpleasant symptoms of headache, nausea, flushing,
and tachycardia are experienced by people who lack aldehyde dehydrogenases and who drink; this is believed to be
because of accumula on of acetaldehyde. Under normal circumstances, acetate is oxidised in the liver and peripheral
ssues to carbon dioxide and water.

On an empty stomach, blood alcohol concentra on peaks about one hour a er consump on, depending on the
amount drunk; it then declines in a more or less linear manner for the next four hours. Alcohol is removed from the
blood at a rate of about 3.3 mmol/hour (15 mg/100 ml/hour), but this varies in different people, on different drinking
occasions, and with the amount of alcohol drunk.drunk.
Figure 4

Concentra ons of alcohol in the blood a er six units of alcohol (equivalent to 48 g alcohol)

At a blood alcohol concentra on of 4.4 mmol (20 mg/100 ml), the curve fla ens out, but detectable concentra ons
are present for several hours a er three pints of beer or three double whiskies in healthy people; enough alcohol to
impair normal func oning could be present the morning a er an evening session of drinking. Alcohol consump on
by heavy drinkers represents a considerable metabolic load—for example, half a bo le of whisky is equivalent in
molar terms to 500 g aspirin or 1.2 kg tetracycline.

Heavy drinkers

Two mechanisms dispose of excess alcohol in heavy drinkers and account for “tolerance” in established drinkers.
Firstly, normal metabolism increases, as shown by high blood concentra ons of acetate. Secondly, the microsomal
ethanol oxidising system is brought into play; this is dependent on cytochrome P450, which is normally responsible
for drug metabolism, and other cofactors. This process is called enzyme induc on, and the effect is also produced by
other drugs that are metabolised by the liver and by smoking.smoking.
Figure 5

Rate of decrease of concentra ons of alcohol in the blood in heavy, social, and naïve drinkers. The two lines
represent maximum and minimum rates for each category

The two mechanisms lead to a redox state, in which free hydrogen ions build up and have to be disposed of by
several different pathways. Some of the resultant metabolic aberra ons can have clinical consequences: hepa c
gluconeogenesis is inhibited, the citric acid cycle is reduced, and oxida on of fa y acids is impaired. Glucose
produc on is thus reduced, with the risk of hypoglycaemia; overproduc on of lac c acid blocks uric acid excre on by
the kidneys; and accumulated fa y acids are converted into ketones and lipids.

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Behavioural effects

Alcohol is a seda ve and mild anaesthe c. It is believed to ac vate the pleasure or reward centres in the brain by
triggering release of neurotransmi ers such as dopamine and serotonin. Alcohol produces a sense of wellbeing,
relaxa on, disinhibi on, and euphoria. These feelings are accompanied by physiological changes such as flushing,
swea ng, tachycardia, and increases in blood pressure, probably because of s mula on of the hypothalamus and
increased release of sympathomime c amines and pituitary-adrenal hormones. The kidneys secrete more urine, not
only because of the fluid drunk but also because of the osmo c effect of alcohol and inhibi on of secre on of
an diure c hormone.hormone.
Figure 6

Effect of alcohol on behaviour

Increasing consump on leads to a state of intoxica on, which depends on the amount drunk and previous
experience of drinking. Even at a low blood alcohol concentra on of around 6.5 mmol/l (30 mg/100 ml), the risk of
uninten onal injury is higher than in the absence of alcohol, although individual experience and complexity of task
have to be taken into account. In a simulated driving test, for example, bus drivers with a blood alcohol concentra on
of 10.9 mmol/l (50 mg/100 ml) thought they could drive through obstacles that were too narrow for their vehicles. At
17.4 mmol/l (80 mg/100 ml)—the current legal limit for driving in the United Kingdom—the risk of a road traffic
incident more than doubles, and at 34.7 mmol/l (160 mg/100 ml), it increases more than 10-fold.

People become garrulous, elated, and aggressive at concentra ons above 21.7 mmol/l (100 mg/100 ml) and then
may stop drinking as drowsiness supervenes. A er effects (“hangover”) include insomnia, nocturia, redness,
nausea, and headache.

If drinking con nues, slurred speech and unsteadiness are likely at around 43.4 mmol/l (200 mg/100 ml), and loss of
consciousness may result. Concentra ons above 86.8 mmol/l (400 mg/100 ml) commonly are fatal as a result of
ventricular fibrilla on, respiratory failure, or inhala on of vomit (this is par cularly likely when drugs have been
taken in addi on to alcohol).alcohol).
Figure 7

Risks associated with concentra ons of alcohol in the blood

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Notes

The figure showing the metabolism of ethanol is adapted from C S Lieber et al. N Engl J Med 1978;298: 356 [Google
Scholar]. The figure showing the effect of alcohol on behaviour is adapted from Transport and Road Research
Laboratory. The facts about drinking and driving. Crowthorne: Berkshire, 1983. The figure showing concentra ons of
alcohol in the blood in heavy, social, and naïve drinkers is constructed from figures supplied by K Lewis BMJ
1987;295: 800-1 [PMC free ar cle] [PubMed] [Google Scholar].

Compe ng interests: None declared.

The ABC of Alcohol is edited by Alex Paton, re red consultant physician, Oxfordshire (moc.loa@xelAnotaP) and Robin
Touquet, consultant in accident and emergency medicine, St London ([email protected])