Alcohol spreads quickly through the body and can easy penetrate the cells and tissues of every organ. It is eliminated in various ways. A small amount is eliminated in unchanged state, partly through the lungs (fetor alcoholicus) directly related to the level of alcohol in the blood, and partly through the kidneys. Most of it is metabolized.
This is done partly in the mucous membrane of the stomach by the enzyme alcoholdehydrogenase (ADH). Stomach ADH is much more active in men than in women, so that women with the same oral consumption of alcohol as men have a higher concentration in the blood. (note 38)
Most of the metabolism is done in the liver, which has two systems at its disposal:
1. The alcoholdehydrogenase system
ADH catalyses the oxidation of alcohol to acetaldehyde. Acetaldehyde is then oxidized to acetate under the influence of the enzyme aldehydedehydrogenase (ALDH), resulting in the production of lactic acid: the body acidizes: lactatacidosis. This is at the expense of carbohydrate metabolism and can result in hypoglycaemia (an excessively low concentration of sugar in the blood).
2. The microsomal ethanol oxidation system (MEOS)
The MEOS system is particularly active with high concentrations 'of alcohol. This enzyme system also breaks alcohol down to acetaldehyde. Under continuous stimulation, this system grow develop stronger and stronger, so that a larger volume of alcohol per unit of time can be broken down under constant use. Other substances are also metabolized in the MEOS system, whose effects are influenced by alcohol.
The elimination of alcohol from a non-chronic drinker is linear. The liver requires around one and a half hours to eliminate one standard consumption (10 grams).
There is no linear relation between the level of alcohol in the blood and the degree of intoxication: there are great differences in the effects of alcohol from one individual to another.
As a result of the activity of the enzymes in metabolism, the percentage of alcohol in the blood is never constant over a longer period. It rises rapidly after consumption, but then drops steadily. The effects of alcohol are experienced as pleasurable during the rising part of the curve. The effect is less pleasurable when the same concentration is in the falling part of the curve.
The biochemical consequences of the metabolism of alcohol
The most harmful effects of alcohol use are caused by the metabolite products: acid and acetaldehyde. Alcohol itself has few harmful effects.
Besides the formation of lactic acid, the oxidation of fatty acids is also disturbed. Fatty acids which are not broken down accumulate in the liver cell, resulting in fatty liver. The liver tries to reduce this accumulation of fatty acids by eliminating them into the blood. The result is hyperlipemia, an excess of fat in the blood, which contributes to arteriosclerosis.
Most of the acetaldehyde is rapidly turned into acetate, but a small percentage escapes to the blood and produces effects elsewhere in the body. Acetaldehyde can damage cells, thereby slowing down the rate at which the acetaldehyde is metabolized. In the liver, acetaldehyde disturbs the protein metabolism, resulting in protein accumulation and extra expansion of the liver.
The acetaldehyde which escapes to the blood can encourage the release of adrenaline and dopamine, but in general the level of concentration of acetaldehyde is too low for that. There are two exceptions:
1. Asians are particularly affected by a genetically determined acceleration in the production of acetaldehyde, which can result in tachycardia, transpiration, headache, paleness and nausea after the consumption of only small quantities of alcohol.
2. The same symptoms occur as a reaction to disulfiram (Antabus, Refusal). Disulfiram inhibits ALDH, resulting in a rapid accumulation of acetaldehyde after the consumption of alcohol.
The virtually complete blocking of ABDH leads to a heavy reaction around 5 to 15 minutes after the consumption of alcohol a result of the release of catecholamines.
Influence on the neurotransmitters
Generally speaking, the effect in the brain is one of inhibition, including the inhibitory systems. As a result of this weakening of the inhibitory systems, the use of alcohol can result in a more easy-going atmosphere and social contacts seem to proceed more smoothly and rapidly (apparent activation).
The acetaldehyde, natural amines (such as dopamine and serotonin) and their metabolite complexes form the so-called tetra-hydro-iso-quinolin derivatives (TIQs). As a result of the rapid formation of these complexes, the concentration of acetaldehyde in the blood of alcoholics remains relatively low. The two main TIQs are tetrahydropapaverolin (THP) and salsolonol. The TIQS interact in the CNS with the opiate receptors .(note 39) It is possible that this mechanism plays a role in the origin of alcohol dependence, which would then have the same neurobiochemical basis as addiction to opiates, since TIQs are morphine-like substances. This hypothesis is confirmed by the finding that the administering of naloxon also counteracts the objective effects of alcohol intoxication, but not the subjective ones.(note 40)
Alcohol, or its metabolites, also affects the GABA receptors. An experimental substance (Rol5-4513, a benzodiazepine derivative) apparently attaches itself to the GABA receptors and thereby blocks the effects of alcohol, while administering a substance which blocks the GABA receptors in turn blocks the effect of Rol5-4513. (notes 41 42)
Alcohol also influences the glutamate (NMDA) receptor.
When alcohol is administered to test animals in large doses, the serotonin production increases significantly. If we perceive that the concentration of 5-HIAA (the most important serotonin metabolite) is low in alcoholics when they do not drink, it may be supposed that the use of alcohol is a form of self-medication to correct an excessively low serotonin production.(5)
Finally, alcohol also affects the metabolism of noradrenaline and dopamine: an increase in NA production after chronic use and an increase in DA production after acute use. Tolerance for the DA effect occurs under chronic use. (5)
Alcohol tolerance occurs after prolonged alcohol use: based on adaptation in the CNS and metabolic tolerance, based on the increased capacity of the MEOS. This enzyme system also has a function in the breaking down of medicaments such as anticoagulants, benzodiazepines, barbiturates and narcotics, so that the capacity of these substances to metabolize increases as well. This makes it difficult to prescribe medicines for patients who have been using alcohol in large quantities for a long time. The strengthening of the effect of benzodiazepines and barbiturates by alcohol probably proceeds via the influence of alcohol on the GABA receptors. Many alcohol users are only too aware that the effect of the alcohol is reinforced by librium, and make use of this fact.
Alcohol and nutrition
Although alcohol yields 7.1 kcal per gram, it cannot be regarded as a foodstuff because it does not supply any of the inputs required by the body. They are redundant calories. Partly as a result of this supply of calories, chronic drinkers do not feel hungry, which can easily lead to deficits of proteins, vitamins and trace elements. Alcohol also disturbs digestion and resorption through changes in the structure and function of the small intestine, liver and pancreas. Finally, deficient nutrition can result in atrophy of the small intestine, causing resorption malfunctioning. An adequate diet cannot prevent the various forms of malnutrition.
The major deficiencies are in vitamin B1, which can be seen in polyneuropathy and the Wernicke-Korsakoff syndrome, and in folic acid, resulting in megaloblastic anaemia.
Clinical effects of alcohol abuse
An increased risk of the emergence of carcinomas in the upper part of the digestive system; this risk is even higher when combined with smoking. Disturbances of the peristaltic and the tension of the sphincters (acidity and flatulence). Gastritis: nausea, pain in the upper abdomen, morning sickness and vomiting blood. Stomach ulcers. Increase of the production of mucous in the small intestine and drop in intestinal motility, resulting in diarrhoea and villus atrophy, in turn leading to nutritional deficiencies.
Acute, recurrent and chronic pancreatitis. Chronic pancreatitis is resistant. Stopping the use of alcohol does not help any more.
The following conditions can occur simultaneously: hepatitis, fibrosis and cirrhosis. Eventually the liver function becomes highly disturbed, with consequences for many bodily functions: a blood coagulation disorder, intoxication by normal doses of medicines, or encephalopathy.
The ability of the heart to contract is reduced, eventually leading to a cardiomyopathy. Arrhythmia's also occur. Sudden death from heart failure is commoner among alcoholics, probably due to a combination of an arrhythmia with coronary sclerosis. Despite the existence of hyperlipemia, some studies have shown that the risk of coronary sclerosis is lower among drinkers than among non-drinkers.
Megaloblastic anaemia as a consequence of a shortage of folic acid and haemolytic anaemia through a direct toxic effect of acetaldehyde. Thrombocytopenia, a deficiency of blood platelets, leads to coagulation disorder.
A reduction in the elimination of uric acid can lead to an attack of gout. Alcohol also brings about a suppression of the antidiuretic hormone, resulting in increased urine production, which may lead to hydration.
Neurological and psychiatric consequences
For acute alcohol intoxication see the following table.
0/00 no. glasses consequences
0.2 1 commencement of alteration of mood and
0.5 2 - 3 legal limit for driving
1 4 - 5 unsteadiness, limit of what is socially
2 ~ 10 vomiting, ataxia, seeing double, blackouts
3 + 15 speechlessness and depressed respiration,
insensitivity to pain
3.5 - 4 + 20 apnoea
with higher concentrations, the heart stops
The effects of these percentages apply to moderate drinkers.
Further neurological complications are:
- A symmetrical polyneuropathy affecting the tips of the fingers and toes, so that disturbances of the senses come to the fore: 'Bugs are creeping over my arm'.
- Myopathy would be a direct result of the toxic influence of alcohol. It can be acute or chronic.
- The Wernicke-Korsakoff syndrome is mainly the result of a vitamin B1 deficiency. The symptoms are: constant heavy psychic disturbances: disorientation in relation to space, time and people; disturbance of the memory in the sense of an imprinting disturbance, often with a euphoric character; confabulations; double paralysis of the eye muscle; bleeding in the retina. Anatomically, small bleeding can be observed, deep in the brain. Unless treated, this syndrome is fatal. The treatment consists of the administration of high doses of vitamin B1.
- Sleep disturbances in the sense of a changed sleep structure: earlier waking and suppression of REM sleep (when dreaming is done), despite the use of alcohol as a night-cap.
The reduction or cessation of prolonged heavy use of alcohol is followed by heavy tremors and a number of the following symptoms: nausea or vomiting, malaise, tachycardia, transpiration, increased blood pressure, anxiety, depression or irritability, passing hallucinations or illusions, headache, sleeplessness. As a result of the interaction of biological, psychic and environmental factors, an alcohol withdrawal delirium can occur: reduced level of consciousness, disorientation, memory disturbances, delusions, and hallucinations (usually visual) with very restless and agitated behavior.
Alcohol hallucinosis can also occur, which is characterised by lively acoustic hallucinations while the consciousness remains clear. The content of the hallucinations is often disturbing and unpleasant for the addict, sometimes to such an extent that the addict seeks protection, for example from the police.
Alcohol and pregnancy
The use of alcohol can have consequences for the foetus. Both alcohol and acetaldehyde are toxic for the embryo and affect the function of the placenta. A combination of serious disorders can occur, which are labelled as a whole as the foetal alcohol syndrome (FAS). The symptoms of this syndrome are as follows:
* prenatal and postnatal inhibition of growth
* neurological anomalies
* dysmorphy of the face
* other congenital anomalies (extremities, heart and kidneys).
These symptoms are never all present in the same child. It is much commoner to see a child with symptoms which do not match the definition of FAS. In this case, they are regarded as fetal alcohol effects (FAE), the most important of which is inhibition of growth. It is likely that other factors play a part besides alcohol, since only 2.5 to 10% of alcoholic mothers give birth to a child with full FAS. FAS children are not addicted to alcohol It seems safest to advise women who intend to get pregnant or who are already pregnant to limit their consumption of alcohol to less than 1 unit a day.
Alcohol and heredity
During the last few years signs have emerged from research on twins and adoption, and from the fact that people with a family history of alcoholism appear to react differently to alcohol from people without such a family background, that alcoholism may have a hereditary basis. Various researchers (notes 43 44) have shown that the sons of alcoholic fathers are influenced by alcohol at a significantly lower rate than the sons of non-alcoholic fathers. It is possible that they go on drinking for longer because they perceive the negative effects of alcohol more slowly.
It has also been shown that rats bred for a preference for alcohol have more GABA receptors in the nucleus accumbens than rats bred for a dislike for alcohol. (note 45) Finally, there appear to be differences between the cerebellar GABA-beta receptors of alcohol-tolerant and alcohol-intolerant families of rats.(note 46) There are thus indications that a genetic component, interacting with environmental factors, plays a part in alcoholism. Proof from genetic research, however, has not yet been supplied. (note 47)
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