Goals: In this
session you will be introduced to:Merlexi Craft: See
"Alcohol" is a generic name for large group of organic chemical compounds. They all are derivatives of hydrocarbons in which one or more of the hydrogen atoms have been replace by a hydroxyl (-OH) functional group. Hydrocarbons are compounds with contain hydrogen (H) and carbon (C) only. The hydroxyl group imparts particular properties to the radical to which it is attached.
Alcohols are named according to the radical to which the OH group is attached. For example if the OH group is attached to the methyl radical CH3 so that the compound is CH3OH, then one has methyl alcohol. If it is attached to the ethyl (C2H5) radical then one has ethyl alcohol (CH3CH2OH) - the alcohol we consume in beverages.. The general formula for alcohol is ROH, where R signifies a hydrocarbon radical attached to an -OH group. A list of some of the common alcohols is given below:
Ethyl Alcohol - for which the more scientific name is ethanol - is the substance that we find in beverages. For the remainder of this unit, consider the words ethyl alcohol, alcohol and ethanol to be interchangeable. An alternate representation of ethyl alcohol as a "ball and stick" molecular model appears below - white spheres represent hydrogen, black - carbon and red - oxygen:
Ethyl alcohol is a colorless liquid at room temperature. It boils at 78 degrees Celsius at atmospheric pressure and freezes at -114 degrees Celsius. Ethyl alcohol mixes in all proportions with water - the two substances are mutually soluble. It is flammable and will burn in air when there is between 3 and 19% ethanol in the vapor.
Ethanol is an excellent solvent and many industrial and consumer products are based on materials dissolved in alcohol. And ethyl alcohol is the alcohol we find in concentrations up to above 50% in alcoholic beverages.
Hydration of ethylene is the primary method for the industrial production of ethyl alcohol, while fermentation is the primary method for production of beverage alcohol.
Ethyl alcohol (ethanol, CH3CH2OH) is a low molecular weight aliphatic (open chain) compound, which is completely miscible with water. This characteristic is due to its hydroxyl (-OH) group, which forms intermolecular hydrogen bonds to water. Thus, the hydroxyl group is referred to as being hydrophilic (water-attracting), whereas the ethyl (C2H5-) group is hydrophobic (water-repelling).
Because of the complete miscibility with water, ethyl alcohol is readily distributed throughout the body in the aqueous blood stream after consumption. Also and because of this water solubility, it is readily crosses important biological membranes, such as the blood brain barrier, to affect a large number of organs and biological processes in the body.
Absorption of ethyl alcohol into the blood can occur through the skin and via the lungs, though the major route of taking ethyl alcohol into the body is by drinking alcoholic beverages.
Ethyl alcohol distributes in the body in proportion to the water content in the particular tissue. Ethyl alcohol crosses with water into the blood stream, therefore the process of distribution of alcohol is rapid. The more one drinks, the more alcohol would be in the blood.
Since ethyl alcohol mixes freely with water it would be expected that within the blood, alcohol distribution would parallel the distribution of water in the blood. Since plasma and serum have approximately the same water content (92%), whereas whole blood has about 80% water, it would be expected that the ratio of ethyl alcohol content in the plasma or serum to alcohol content in whole blood would be equal to the ratio of water in plasma to the water in whole blood. This is what was found, in that the ratio was approximately 1.12 for both (92%/80% = 1.15). Since water diffuses easily across cell membranes through aqueous channels, including vascular endothelium it is expected that ethyl alcohol would do the same. Further it is expected that the ethyl alcohol concentration in the tissues would rapidly reach equilibrium with the ethyl alcohol in the blood. This is certainly been found to be the case.
Another system in the liver which oxidizes ethanol via the enzyme cytochrome P450IIE1 (CYP2E1) is called the MEOS system. The reaction catalyzed by MEOS is:
CH3CH2OH + NADPH + O2 -> CH3CHO + NADP+ + H2O.
Though of minor significance in comparison to ADH metabolism of ethanol, the MEOS system seems to play an increasingly important role at higher concentrations of ethanol. It is not surprising that there are variations in the P450E1 enzyme which lead to differences in the rate of ethanol metabolism. This may have implications for tissue damage from ethanol, particular in the liver.
Alcohol affects many body systems. This section offers only a brief summary. You can see in depth information elsewhere in this unit.
Alcohols action on the brain produces of a number of behavioral effects. These effects are dependent upon the
3. Alcoholic cirrhosis This is the most advanced form of liver disease and is diagnosed in 15 to 30 % of heavy drinkers. Between 40 and 90 percent of the 26,000 annual deaths form cirrhosis are alcohol related. Cirrhosis is characterized by extensive scar tissue (fibrosis) that stiffens blood vessels and distorts the internal structure of the liver. Cirrhosis causes malfunction of other bodily organs such as the brain and kidneys.
Kidney: The major functions of the kidneys are to regulate the volume and composition of the fluids and electrolytes in the body. They help in the supply of nutrients to the cells of the body and in clearing cellular waste as well as providing stable conditions for the cells to function. The substances regulated by the kidneys include water, sodium, potassium, calcium, and phosphate in the fluids surrounding the various cells. In addition the kidneys regulate the acid-base balance which is important in maintaining cell structure, permeability, and metabolic activity. Further, the kidneys produce hormones that influence numerous physiological processes. Because of their involvement in all these important bodily processes, alcohol, has the potential to influence and/or compromise these functions of the kidneys and thus has the potential to induce severe consequences for the functioning of the organism.
As with most organs in the body there are a number of regulatory processes which allow the kidney to function normally and optimally, ethyl alcohol can disturb these controls. The precise effects depend upon the amount of alcohol taken and the time over which it is consumed. Alcohol has been shown to change the structure and function of the kidney and impair their ability to regulate the volume and composition of fluid and electrolytes in the body.
Gross and microscopic changes in the kidney include alterations in the structure of the glomerulus, swelling or enlargement (nephromegaly) of the kidney, and increased number of cells with fat, protein, and water. These effects alter the ability of the kidneys to function normally.
The rate of blood flow through the kidneys is an important determinant of the amount of filtration of the blood and absorption of substances from the blood that can take place. Various effects of alcohol have been reported including both increased and reduced blood flow. These effects seem to be related to whether or not the person also had liver disease and in animal models which species of animal was used.
Alcohols on electrolyte balance has major implications for the satisfactory functioning of the cells of the body. As a prime example, the cells of the brain and particularly neurons are highly dependent upon proper amounts of sodium, potassium, chloride, and calcium being available. Disruption in the proper flow and availability of these electrolytes alters the ability of the neurons to function which leads to modifications in behavior and the ability of the brain to regulate other bodily processes.
Ethyl alcohol can induce urine flow within 20 minutes. As a result of these fluid losses the concentrations of electrolytes in the blood can changed and can be dramatic, particularly in cases of extreme loss of water. Ethyl alcohol appears to affect a hormone called antidiuretic hormone, which induces the kidney to conserve fluids. This effectively concentrates the urine. Ethyl alcohol decreases the ability of the body to concentrate urine, thus promotes water loss rather than allowing the water to be absorbed back into the body. As a result of this electrolyte levels in the blood also rise due to less water being taken back in.
Proper acid-base balance (i.e. hydrogen ion concentration) is crucial to the proper functioning of most of the bodys metabolic reactions. The kidneys play an important role in regulating this acidity, thus the rate at which metabolic processes proceed. Examples of alcohol-related acid-base disturbances include low levels of phosphate, which may result from hyperventilation during withdrawal from alcohol and cases of alkalosis (low acidity) which may be a result of severe vomiting after binge drinking. The latter sickness leads to losses of fluid, salt, and stomach acid.
Alcohol and the Fetus:
Drinking ethanol while pregnant is the same as feeding ethanol to the baby. Since ethanol freely mixes with the body water through diffusion, it is rapidly distributed into the blood. Since the mothers blood circulation is connected to that of the fetus, the alcohol is rapidly transported to the fetus to be distributed in the cells and tissues of the infant and into the fluid surrounding the fetus.
Once distributed, alcohol has the opportunity to directly influence the growth and development of the child. Alterations by ethanol in the function of growth factors and other chemical mediators known to be important in guiding the development of the fetus have in fact been amply demonstrated. At the extreme the child can be born with Fetal Alcohol Syndrome (FAS)>
Ethanol can also influence fetal development indirectly by exerting effects on the mother, which in turn influence the fetus. These indirect effects can include altering the nutritional status of the mother so that the fetus gets less nutrition; altering the function of the placenta, so that fewer nutrients and/or oxygen gets to the fetus; producing metabolites of ethanol such as acetaldehyde, which is known to be toxic; and compounding the effects of other drugs (therapeutic and nontherapeutic) that mother might be taking.
The degree of damage incurred by the fetus is influenced by several factors, including the period of gestation when alcohol exposure occurs, how much the mother drinks during pregnancy, the pattern and timing of her drinking, and the genetic makeup of both mother and child. Because of these factors and others, it is not possible to know what level of drinking is safe for each individual, and so abstinence is recommended to all women who are pregnant, nursing, or who may become pregnant.
Alcohol and the Heart:
It is clear that of all the systems in the body the cardiovascular system is the one where ethanol may have both positive and negative effects. As with most other alcohol action, the precise effects of the alcohol are dependent upon amount taken in, timing of intake, history of drinking, genetics, and physical status of the person doing the drinking. In general, a person with good health and no history of alcoholism or cardiovascular disease, drinking a small or moderate amount of ethanol may receive beneficial effects. Moderate drinking is defined as drinking one or two drinks per day. In contrast, drinking heavy amounts, i.e. greater than two drinks per day, may have deleterious effects.
In summary, ethanol consumption can be both beneficial and harmful to the cardiovascular system. The precise outcome for any one individual is hard to predict, nevertheless as a general guide one can use the information in the Table below.
What accounts for the ability of some to drink without difficulty in contrast to those who become "addicted"?
Some individuals are more vulnerable than others to becoming addicted. This enhanced vulnerability can be ascribed to genetic (biochemically regulated vulnerability) as well as environmental factors (situational impact). It is also clear that people without an apparent enhanced vulnerability can be addicted to ethanol.
What is the current thinking about biochemical basis of addition? Two general processes contribute to alcohol addiction.
Types of rewarding (positive) experiences gained after drinking include the taste of the alcohol itself and the feelings (e.g. relaxation) gained after drinking ethanol. One can also gain a positive experience by avoiding negative situations such as those felt in anxiety provoking situations (public speaking, attending a party) or avoiding the effects of withdrawal from ethanol (see below). The rewarding aspects of ethanol use involve the brains reward system. This system is comprised of brain structures and circuitry (e.g. ventral tegmental area, extended amygdala and the nucleus accumbens within) that appears to be important in the reinforcing (rewarding) properties of a variety of drugs.
The second process important in addiction has to do with the ability of the brain to adapt to influences, which affect its normal function. The ability is called neuroadaptation. For example, the drinking of one or two beers or one or two drinks (acute intake of ethanol) activates a variety of processes in the body and in particular impacts the functioning of the brain.
In order to keep the brain functioning normally, the brain attempts to chemically counteract whatever ethanol is doing to disrupt its action. A simple illustration is the reaction of the body if someone starts pushing it. The natural reaction is to compensate by correcting the balance and attempting to counteract the pressure of the push until the push is gone and the body returns to normal. Interestingly, neuroadaptation also sometimes results in an increased response to the drug (sensitization). Whether there is a diminished response or an enhanced response depends upon a variety of factors including the amount of the compound taken in and the timing of the intake. The development of sensitization to drugs such as cocaine may be more likely with intermittent exposure than with continuous exposure.
Ethanol acts at specific sites on a specific subset of GABA and glutamate receptors (protein molecules upon which the neurotransmitters act). By influencing the action of these receptors, ethanol "slows down" the functioning of the nervous system. Thus, ethanol is called a central nervous system (CNS) depressant.
With neuroadaptation, the brain attempts to counteract this depressant effect by increasing the activity of the glutamate system and decreasing the activity of the GABA system. This in part can be accomplished by altering the number or function of the receptors.
GABA and glutamate receptors are only two of a number of key players in the transmission of information from one cell to the next. Activation of receptors is the occasion for intracellular signaling, meaning that a series of events within the cell take place when a neurotransmitter binds to the receptor. Thus, neuroadaptation can also take place at other locations within the cascade of events that take place in the brain.
Just as there is adaptation upon the presence of something new, there is neuroadaptation when the compound leaves the brain. Thus, through neuroadaptation the brain is able in many instances to up-regulate (increase) or down-regulate (decrease) its function to compensate for the presence or absence of ethanol. (It should be recognized that the body and the brain have an amazing ability to adapt and only in extreme situations or after damage, such as seen in alcoholism, do the regulatory processes fail).
If a person chooses to drink more regularly (chronic intake), the brain attempts to adapt to the increasing amounts of ethanol. Generally, neuroadaptation can take place up to a point. After chronic consumption and ongoing adaptation, it will now take more ethanol to produce the same effect as the first drink. When this is the case, tolerance has developed and substantial adaptation has taken place. If the person now chooses to quit drinking the body tries to return to its original state in doing so causes a number of withdrawal signs including tremors, seizures, nausea, and negative emotional states. Since further drinking will delay, diminish, or prevent withdrawal, the person often chooses to drink again. Even if the person stops drinking, the neuroadaptations that took place in the brain may persist for a period of time well beyond the time when ethanol is no longer present in the body. It has been speculated that these may be the source of the urges to drink again.
For most people it is relatively easy to modulate ethanol intake. Depending upon the vulnerability of the individual, as drinking progresses regulation of drinking becomes more difficult. Simultaneously, the ability of the brain to adapt is diminished or lost. Systems become increasingly disregulated, perhaps due to damage, so that in the brain communication and coordination diminishes or fails. This is particularly true after repeated withdrawals from ethanol, since the severity of withdrawal increases. Perhaps this is the reason for saying the drink appears to take on a life of its own.
"First the person takes a drink, then the drink takes a drink, then the drink takes the person".
In general there appears to be a general loss of control. The individual has lost control over drinking and neuroadaptive mechanisms have been overwhelmed. Thus alcoholism can be characterized as a disease with takes over the body and brain.
The environment associated with drinking is now known to play a crucial role in the addictive process. The environment associated with the drinking becomes associated with the positive attributes of drinking. Thus, it common knowledge that if one always drinks in a particular bar, or with cigarette in their hand, or with a certain group of friends, then the bar, cigarette, and friends can trigger the urge to drink. This is because the bar, cigarette, and friends have become cues associated with drinking and can trigger the brain reward system in a manner somewhat similar to that seen with the ethanol. Attempts to help alcoholics return to normal functioning must include understanding of the important role of cues in addiction.