Alcohol in the body
http://www.100md.com
《英国医生杂志》
Introduction
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 relatively slowly absorbed from the stomach, more rapidly absorbed from the small intestine, 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 active man is 3000 kcal and for a woman 2200 kcal.
Absorption
Rate of absorption of alcohol depends on several factors. It is quickest, for example, when alcohol is drunk on an empty stomach and the concentration of alcohol is 20-30%. Thus, sherry, with an alcohol concentration of about 20% increases the levels of alcohol in blood more rapidly than beer (3-8%), while spirits (40%) delay gastric emptying and inhibit absorption. Drinks aerated with carbon dioxide—for example, whisky and soda, and champagne—get into the system quicker. Food, and particularly carbohydrate, retards absorption: blood concentrations 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.
Rate of absorption of alcohol (arrows) is affected by concentration of alcohol
Alcohol is distributed throughout the water in the body, so that most tissues—such as the heart, brain, and muscles—are exposed to the same concentration of alcohol as the blood. The exception 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.
Most tissues are exposed to the same alcohol concentration as in the blood
Other factors
Very little alcohol enters fat because of fat's poor solubility. Blood and tissue concentrations 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 absorption. Alcohol enters the fetus readily through the placenta and is eliminated by maternal metabolism.
Blood alcohol concentration varies according to sex, size and body build, phase of the menstrual cycle (it is highest premenstrually and at ovulation), previous exposure to alcohol, type of drink, whether alcohol is taken with food or drugs, such as cimetidine (which inhibits gastric alcohol dehydrogenase) and antihistamines, phenothiazines, and metoclopramide (which enhance gastric emptying, thus increasing absorption).
Metabolism of ethanol
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 oxidation by alcohol dehydrogenases, of which at least four isoenzymes exist, to acetaldehyde in the presence of cofactors. Acetaldehyde is a highly reactive and toxic substance, and in healthy people it is oxidised rapidly by aldehyde dehydrogenases to harmless acetate.
This article is adapted from the 4th edition 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 accumulation of acetaldehyde. Under normal circumstances, acetate is oxidised in the liver and peripheral tissues to carbon dioxide and water.
On an empty stomach, blood alcohol concentration peaks about one hour after consumption, 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.
Concentrations of alcohol in the blood after six units of alcohol (equivalent to 48 g alcohol)
At a blood alcohol concentration of 4.4 mmol (20 mg/100 ml), the curve flattens out, but detectable concentrations are present for several hours after three pints of beer or three double whiskies in healthy people; enough alcohol to impair normal functioning could be present the morning after an evening session of drinking. Alcohol consumption by heavy drinkers represents a considerable metabolic load—for example, half a bottle 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 concentrations 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 induction, and the effect is also produced by other drugs that are metabolised by the liver and by smoking.
Rate of decrease of concentrations of alcohol in the blood in heavy, social, and na?ve 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 aberrations can have clinical consequences: hepatic gluconeogenesis is inhibited, the citric acid cycle is reduced, and oxidation of fatty acids is impaired. Glucose production is thus reduced, with the risk of hypoglycaemia; overproduction of lactic acid blocks uric acid excretion by the kidneys; and accumulated fatty acids are converted into ketones and lipids.
Behavioural effects
Alcohol is a sedative and mild anaesthetic. It is believed to activate the pleasure or reward centres in the brain by triggering release of neurotransmitters such as dopamine and serotonin. Alcohol produces a sense of wellbeing, relaxation, disinhibition, and euphoria. These feelings are accompanied by physiological changes such as flushing, sweating, tachycardia, and increases in blood pressure, probably because of stimulation of the hypothalamus and increased release of sympathomimetic amines and pituitary-adrenal hormones. The kidneys secrete more urine, not only because of the fluid drunk but also because of the osmotic effect of alcohol and inhibition of secretion of antidiuretic hormone.
Effect of alcohol on behaviour
Increasing consumption leads to a state of intoxication, which depends on the amount drunk and previous experience of drinking. Even at a low blood alcohol concentration of around 6.5 mmol/l (30 mg/100 ml), the risk of unintentional 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 concentration 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 concentrations above 21.7 mmol/l (100 mg/100 ml) and then may stop drinking as drowsiness supervenes. After effects ("hangover") include insomnia, nocturia, tiredness, nausea, and headache.
If drinking continues, slurred speech and unsteadiness are likely at around 43.4 mmol/l (200 mg/100 ml), and loss of consciousness may result. Concentrations above 86.8 mmol/l (400 mg/100 ml) commonly are fatal as a result of ventricular fibrillation, respiratory failure, or inhalation of vomit (this is particularly likely when drugs have been taken in addition to alcohol).
Risks associated with concentrations of alcohol in the blood
Further reading
? Lewis KO. Back calculation of blood alcohol concentration. BMJ 1987;295: 800-1
? Lieber CS, Salaspuro MP. Alcoholic liver disease. In: Millward-Sadler CHM, Wright R, Arthur MJP, eds. Wright's liver and biliary disease, 3rd ed. London: Saunders, 1992: 899-964
? Paton A. The body and its health. In: Cooper DB, ed. Alcohol use. Oxford: Radcliffe, 2000: 25-38.
The figure showing the metabolism of ethanol is adapted from C S Lieber et al. N Engl J Med 1978;298: 356. 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 concentrations of alcohol in the blood in heavy, social, and na?ve drinkers is constructed from figures supplied by K Lewis BMJ 1987;295: 800-1.
Competing interests: None declared.
The ABC of Alcohol is edited by Alex Paton, retired consultant physician, Oxfordshire (PatonAlex@aol.com) and Robin Touquet, consultant in accident and emergency medicine, St London (R.Touquet@imperial.ac.uk)(Alex Paton)
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 relatively slowly absorbed from the stomach, more rapidly absorbed from the small intestine, 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 active man is 3000 kcal and for a woman 2200 kcal.
Absorption
Rate of absorption of alcohol depends on several factors. It is quickest, for example, when alcohol is drunk on an empty stomach and the concentration of alcohol is 20-30%. Thus, sherry, with an alcohol concentration of about 20% increases the levels of alcohol in blood more rapidly than beer (3-8%), while spirits (40%) delay gastric emptying and inhibit absorption. Drinks aerated with carbon dioxide—for example, whisky and soda, and champagne—get into the system quicker. Food, and particularly carbohydrate, retards absorption: blood concentrations 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.
Rate of absorption of alcohol (arrows) is affected by concentration of alcohol
Alcohol is distributed throughout the water in the body, so that most tissues—such as the heart, brain, and muscles—are exposed to the same concentration of alcohol as the blood. The exception 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.
Most tissues are exposed to the same alcohol concentration as in the blood
Other factors
Very little alcohol enters fat because of fat's poor solubility. Blood and tissue concentrations 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 absorption. Alcohol enters the fetus readily through the placenta and is eliminated by maternal metabolism.
Blood alcohol concentration varies according to sex, size and body build, phase of the menstrual cycle (it is highest premenstrually and at ovulation), previous exposure to alcohol, type of drink, whether alcohol is taken with food or drugs, such as cimetidine (which inhibits gastric alcohol dehydrogenase) and antihistamines, phenothiazines, and metoclopramide (which enhance gastric emptying, thus increasing absorption).
Metabolism of ethanol
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 oxidation by alcohol dehydrogenases, of which at least four isoenzymes exist, to acetaldehyde in the presence of cofactors. Acetaldehyde is a highly reactive and toxic substance, and in healthy people it is oxidised rapidly by aldehyde dehydrogenases to harmless acetate.
This article is adapted from the 4th edition 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 accumulation of acetaldehyde. Under normal circumstances, acetate is oxidised in the liver and peripheral tissues to carbon dioxide and water.
On an empty stomach, blood alcohol concentration peaks about one hour after consumption, 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.
Concentrations of alcohol in the blood after six units of alcohol (equivalent to 48 g alcohol)
At a blood alcohol concentration of 4.4 mmol (20 mg/100 ml), the curve flattens out, but detectable concentrations are present for several hours after three pints of beer or three double whiskies in healthy people; enough alcohol to impair normal functioning could be present the morning after an evening session of drinking. Alcohol consumption by heavy drinkers represents a considerable metabolic load—for example, half a bottle 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 concentrations 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 induction, and the effect is also produced by other drugs that are metabolised by the liver and by smoking.
Rate of decrease of concentrations of alcohol in the blood in heavy, social, and na?ve 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 aberrations can have clinical consequences: hepatic gluconeogenesis is inhibited, the citric acid cycle is reduced, and oxidation of fatty acids is impaired. Glucose production is thus reduced, with the risk of hypoglycaemia; overproduction of lactic acid blocks uric acid excretion by the kidneys; and accumulated fatty acids are converted into ketones and lipids.
Behavioural effects
Alcohol is a sedative and mild anaesthetic. It is believed to activate the pleasure or reward centres in the brain by triggering release of neurotransmitters such as dopamine and serotonin. Alcohol produces a sense of wellbeing, relaxation, disinhibition, and euphoria. These feelings are accompanied by physiological changes such as flushing, sweating, tachycardia, and increases in blood pressure, probably because of stimulation of the hypothalamus and increased release of sympathomimetic amines and pituitary-adrenal hormones. The kidneys secrete more urine, not only because of the fluid drunk but also because of the osmotic effect of alcohol and inhibition of secretion of antidiuretic hormone.
Effect of alcohol on behaviour
Increasing consumption leads to a state of intoxication, which depends on the amount drunk and previous experience of drinking. Even at a low blood alcohol concentration of around 6.5 mmol/l (30 mg/100 ml), the risk of unintentional 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 concentration 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 concentrations above 21.7 mmol/l (100 mg/100 ml) and then may stop drinking as drowsiness supervenes. After effects ("hangover") include insomnia, nocturia, tiredness, nausea, and headache.
If drinking continues, slurred speech and unsteadiness are likely at around 43.4 mmol/l (200 mg/100 ml), and loss of consciousness may result. Concentrations above 86.8 mmol/l (400 mg/100 ml) commonly are fatal as a result of ventricular fibrillation, respiratory failure, or inhalation of vomit (this is particularly likely when drugs have been taken in addition to alcohol).
Risks associated with concentrations of alcohol in the blood
Further reading
? Lewis KO. Back calculation of blood alcohol concentration. BMJ 1987;295: 800-1
? Lieber CS, Salaspuro MP. Alcoholic liver disease. In: Millward-Sadler CHM, Wright R, Arthur MJP, eds. Wright's liver and biliary disease, 3rd ed. London: Saunders, 1992: 899-964
? Paton A. The body and its health. In: Cooper DB, ed. Alcohol use. Oxford: Radcliffe, 2000: 25-38.
The figure showing the metabolism of ethanol is adapted from C S Lieber et al. N Engl J Med 1978;298: 356. 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 concentrations of alcohol in the blood in heavy, social, and na?ve drinkers is constructed from figures supplied by K Lewis BMJ 1987;295: 800-1.
Competing interests: None declared.
The ABC of Alcohol is edited by Alex Paton, retired consultant physician, Oxfordshire (PatonAlex@aol.com) and Robin Touquet, consultant in accident and emergency medicine, St London (R.Touquet@imperial.ac.uk)(Alex Paton)