THINGS YOU SHOULD KNOW ABOUT ALCOHOL BEFORE YOU START MAKING AND DRINKING
Even good clean alcohol is bad for you. However if you mess up
and dont do it right. its poisen. and you Die....
- Ethyl alcohol and its place among organic substances
- Industrial and fermentation synthesis of alcohol
- How and where alcohol goes in the body
- Chemistry of alcohol metabolism
- Effect of alcohol on organ function
- Alcohol abuse and addiction
Alcohol and Organic
Substances:
"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:
Alcohol Name
Formula
Methyl alcohol (methanol)
CH3OH
Ethyl alcohol (ethanol)
CH3CH2OH
n - propyl alcohol
CH3CH2CH2OH
Isopropyl alcohol (propanol -2)
CH3CHOHCH3
n-butyl alcohol (butanol -1)
CH3(CH2)2CH2OH
ethylene glycol
CH2OHCH2OH
glycerol
CH2OHCHOHCH2OH
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.
Synthesis of
Alcohol:
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.
Industrial Production:
Industrial ethanol is manufactured via the acid catalyzed hydration of ethylene
by utilization of zeolites or silica aerogels impregnated with phosphoric or
tungstic acid. The distinct advantages of this process are that the reaction
can be a one stage process, the catalyst is regenerated, and concerns about
safety, corrosion, and the environment are diminished. The reaction with
phosphoric acid is as follows:
H2C = CH2 + H2PO3 | O | substrate +H2O -->HOCH2CH3 + H2 PO3 | O | substrate
Of the alcohols produced, ethanol is
particularly useful in industrial applications because of its relatively high
affinity for both water and organic compounds. In order to reduce the need for
strict control and heavy taxation on industrially produced ethanol, the alcohol
is denatured. Denaturing is a process of adding other compounds to the
ethanol to render it unfit for consumption. Denaturants are selected to give
the ethanol a disagreeable taste or odor and in some cases a distinctive color.
In some cases the substances added are toxic and produce gastric disturbances
upon ingestion and/or other unpleasant symptoms. A large number of different
"denaturants" are utilized dependent upon the use for which the ethanol is
intended.
Industrially produced ethanol has many uses
including use in solvent based paints, pharmaceuticals, perfumes, cleaning
products for home and car, lacquers, fuels and inks.
Fermentation and Industrial and Beverage
Production: All beverage alcohol and much of that used in industry is
formed through fermentation of a variety of products including grain such as
corn, potato mashes, fruit juices, and beet and cane sugar molasses.
Fermentation is an enzymatically anaerobic controlled transformation of an
organic compound. With respect to alcohol, we are referring to the conversion
of sugars to ethanol by microscopic yeasts in the absence of oxygen. The
equation for the fermentation of glucose is: C6H1206 -->
in the presence of yeast 2CH3CH2OH+ 2CO2 The figure uses a symbolic notation familiar in
biochemistry. It shows the stepwise transformation of glucose to ethanol through intermediates, pyruvate and acetaldehyde.
The initial fermentation mixture contains
approximately 3 to 5% ethanol such as in beer and up to 12 to 15% ethanol as in
wine and sherry. Higher concentrations of ethanol cannot be achieved by
fermentation, because the yeast becomes inactivated. In this case distillation
is required to generate higher alcohol concentrations.
How
and Where Alcohol Goes in the Body:
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 taken in via
ingestion passes from the mouth down the esophagus and into the stomach and on
into the small intestine. At each point along the way ethyl alcohol can be
absorbed into the blood stream. However, the majority of the ethyl alcohol is
absorbed from the stomach (approx. 20%) and the small intestine (approx. 80%).
In general drinking more alcohol within a certain period of time will result in
increased blood alcohol concentrations (BAC) due to more ethyl alcohol being
available to be absorbed into the blood. However there are a number of factors
that can influence ethyl alcohol absorption from the gastrointestinal tract.
Gastric emptying seems to be the most
important determinant of the rate of absorption of ethyl alcohol taken in
orally. In general the faster the gastric emptying, the more rapid absorption.
Therefore, factors, which influence gastric emptying, influence absorption. One
of the most important factors is the presence of food. Food delays
gastric emptying and therefore delays absorption of ethyl alcohol .
Interestingly, the type of food, whether fat, carbohydrate, or protein, does
not seem to be a factor in the absorption of ethyl alcohol. Physiological
factors such as strenuous physical exercise also delay gastric emptying, thus
decrease ethyl alcohol absorption. Additional factors such as drugs (e.g.
nicotine, marijuana, and ginseng), that modify physiological factors regulating
gastric emptying also modify ethyl alcohol absorption in a predicted
manner.
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.
Alcohol Metabolism:
More than 90% of the
ethyl alcohol that enters the body is completely oxidized to acetic acid. This
process occurs primarily in the liver. The remainder of the alcohol is not
metabolized and is excreted either in the sweat, urine, or given off in one’s
breath. There are several routes of metabolism of ethyl alcohol in the body.
The major pathways involve the liver and in particular the oxidation of ethyl
alcohol by alcohol dehydrogenase (ADH).
As mentioned above perhaps the major route of
metabolism of ethyl alcohol is its oxidation in the liver catalyzed by the
cytosolic enzyme alcohol dehydrogenase (ADH). It catalyzes the following
reaction:
CH3CH2OH +NAD+ -> CH3CHO + NADH + H+.
This reaction produces acetaldehyde, a highly toxic substance.
The second step of ethanol metabolism is
catalyzed by acetaldehyde dehydrogenase. This enzyme converts acetaldehyde to
acetic acid, which is a normal metabolite in humans and hence is non toxic.
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.
Effect
of Alcohol on Organ Function:
Alcohol affects many body systems. This
section offers only a brief summary. You can see in depth information elsewhere in this unit.
Brain:
Alcohol’s direct action on the brain is as a
depressant. It generally decreases the activity of the nervous system. One
could ask how it could be a depressant if after one or two drinks a person
tends to talk more and become more active. The answer is that alcohol can cause
disinhibition, i.e. inhibits cells and circuits in the brain which themselves
are normally inhibitory.
Alcohol’s action on the brain produces of a
number of behavioral effects. These effects are dependent upon the
1. amount of alcohol taken in,
2. the time period over which the
alcohol is drunk,
3. whether other drugs are being
taken at the same time,
4. the previous drinking history
of the individual,
5. the physical state of the
person doing the drinking,
6. the genetic background of the
individual( i.e. ethnicity, gender),
7. the mood and psychological
makeup of the individual and
8. the environment when alcohol is
taken.
Liver:An association between alcohol consumption
and liver disease has been known for over 200 years. In fact, the most common
cause of illness and death from liver disease is from long-term alcohol
consumption. Since the liver is the primary site of alcohol metabolism, it is
not surprising that it is particularly susceptible to alcohol-related injury.
The injury to the liver from long-term drinking apparently comes not only from
ethanol, but also from the dangerous products generated upon the metabolism of
ethanol. These include acetaldehyde and highly reactive molecules called
free radicals. (Free radicals are a group of elements or atoms usually
passing intact from one compound to another, therefore in an uncombined from.
As free, it is usually short lived and highly reactive.)
Normal Liver
Since the liver is the largest
organ in the body (approx. 3.3lbs) and one of the most important being involved
in a number of important processes, it has considerable reserves and is able to
regenerate itself. Therefore, limited damage to the liver can go undetected and
the insult needs to be quite substantial in order for damage to occur. With
respect to alcohol, this means drinking large quantities of alcohol over many
years. It has been estimated (Mazey et al., 1988) that in men the dose needed
would be 600 kilograms taken chronically. This is equivalent to 72 oz of beer,
1 liter of wine, or 5 or 6 standard drinks (1.5oz) daily for 20 years. For
women, the amount needed would be one-fourth of this due to gender
differences in the ability to "handle"
alcohol.
There are three major categories of liver damage from alcohol ingestion, which are usually thought of
as a progression in severity, however this is not always the case. These
are:
1. Fatty liver – Fatty liver means fat
disposition in the liver. This can occur after as single drinking session and
after chronic consumption. Fatty liver is reversible and may not lead to more
serious liver problems.
2. Alcoholic hepatitis – "This disorder
is characterized by widespread inflammation and destruction of the liver". The
liver may have scar tissue. The symptoms may include fever, jaundice and
abdominal pain. The condition may be fatal, but may be reversible if one quits
drinking. It occurs in 50% of heavy drinkers.
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.
Alcohol’s 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 body’s
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.
Moderate Drinking and the Heart Heavy Drinking and The Heart
Reduction of plaque deposits in arteries (atherosclerosis) Increased risk for heart muscle disease (cardiomyopathy)
Protection against blood clot formation (protects against heart attack and stroke)
Increased risk for disturbed heart rhythm (arrhythmia)
Promotion of blood clot dissolution (protects against heart attack and stroke) Increased risk for high blood pressure Increased risk for hemorrhagic stroke
Alcohol Abuse and
Addiction:
What accounts for the ability of some to drink without difficulty in contrast to those who become "addicted"?
Definition of Addiction
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.
- A modified reward process
where by drinking of alcohol provides an overall positive effect
(euphoria or decrease in an unpleasant situation). This is coupled in those
vulnerable individuals with a pattern of diminishing or ignoring the negative
impacts of overconsumption - the hangovers, loss of memory, fights, violence
and arrests. The less vulnerable individual equates heavy alcohol consumption
as overall unpleasant as result of the negative effects outweighing the
positive.
- Neuroadaptation where by the
brain attempts to compensate for something (ethanol) which influences normal
functioning.
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 brain’s 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
- facilitates the action of the major depressant
neurotransmitter in the brain (GABA) and
- inhibits the action of the major excitatory
neurotransmitter in the brain (glutamate).
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.
About Alcoholism
from the National Institute of Alcohol Abuse and Alcoholism
(NIAAA)
he 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.
Acute and chronic alcohol consumption can have
both subtle as well as dramatic effects on the brain and its functioning. The
effects of alcohol on the brain can occur by both direct and indirect means.
Thus, it is not really necessary that the alcohol actually reach the brain,
though it does, for brain function to be modified.
For example, damage to the brain can occur
through alcohol-induced deficiencies in nutrition, liver disease, and through
alterations the function of other bodily systems (e.g. immune, hormonal), which
produce substances which end up in the blood and get transported to the brain.
In the most extreme case, another person who has been drinking could become
violent and injure you, e.g. automobile crashes.
How does ethyl alcohol act in the brain to produce its effects?
Alcohol’s direct action on the
brain is as a depressant. It generally decreases the activity of the nervous
system. One could ask how it could be a depressant if after one or two drinks a
person tends to talk more and become more active. The answer is that alcohol
can cause disinhibition, i.e. inhibits cells and circuits in the brain which
themselves are normally inhibitory.
To understand how alcohol can effect the brain
one needs to know how the brain works. The brain is composed of different
regions or areas as shown. Different regions of the brain are primarily
involved in different activities. For examples, the cerebellum is involved in
coordination of bodily movements; the frontal cortex is primarily involved in
cognitive processes; the occipital lobe contains the visual cortex; and a
portion of the temporal lobe of the cortex is involved in audition. The list
goes on and on.
In order for the parts to communicate with one
another to achieve coordination and allow our bodies to function in a
reasonable manner, the parts are connected by nerve cells also called neurons.
It is estimated that there are 100 billion nerve cells in the brain so one can
visualize the complexity of the inner workings of the brain.
Nerve cells communicate with one another via
electrical and chemical signals. In essence signals coming from outside the
body like light, sound, smells, tastes, and pressure are converted (transduced)
into chemical and electrical signals which pass from one part of the body to
another and from one part of the brain to another.
Once inside the brain
electrical signals and chemical signals continue to be generated to allow
communication between the brain parts and regions. Electrical signals generated
in one neuron causes of the release of chemicals called neurotransmitters (NTs)
from that neuron. These NTs in turn are then available to act at other neurons
in close proximity to the first to either excite or inhibit that neuron’s
activity.
NTs act on neurons by attaching (binding) to
chemical constituents called receptors of the neuronal membrane. There are a
substantial number of different types of receptors for each NT. The binding of
the NT to the receptor is the occasion for a number of secondary responses both
at the membrane level and within the cell. Though there is usually only one or
two NTs released from a particular neuron, numerous NTs bind to each neuron and
their collective action determines the overall response of the neuron. The
resultant response can be the generation of an electrical signal (action
potential) created by changes in ion flow across the nerve cell membrane
(sodium, potassium, and chloride are particularly important) or inhibition of
cellular electrical activity.
There are a substantial number of NTs in the
brain. Four of the most important NTs with respect to alcohol are glutamate,
gamma aminobutyric acid (GABA), dopamine (DA), and serotonin. Glutamate is the
major excitatory NT in the brain. Ethyl alcohol acts to inhibit a subset (N-
methy-D-aspartate, NMDA) of glutamate receptors, thus diminishing the excitatory
actions of glutamate. GABA is the major inhibitory NT in the brain. Alcohol
acts primarily at the GABAa receptor to facilitate its action, thus in essence
creating enhanced inhibition. Changes in the number of both NMDA and GABA
receptors and ability of these receptors to bind their NTs appear to be
involved in the development of tolerance to and dependence on alcohol. The
third important NT in alcohol action, Dopamine, is involved in reward processes
and thus seems to be responsible for the rewarding aspects of alcohol
consumption. Other things that people find rewarding such as food, sex, and
other drugs of abuse also act to release DA in the brain. Serotonin also
appears to play a role in reward processes and therefore seems to be important
in alcohol use and abuse. In addition, serotonin is a prominent player in mood
states, compulsive disorders, aggression, and effects of other drugs of abuse
like methamphetamine and LSD.
It should be recognized that in addition to the
regions or parts of the brain and the billions of neurons in the brain, there
are also various systems. Systems often involve numerous parts just like the
fuel system in a car involves the fuel tank, the fuel pump, the tubing, the
fuel injectors, etc. One important system mentioned above is the reward system,
which plays an important role in the rewarding (reinforcing) properties ethyl
alcohol and other drugs such as cocaine. A major part of the reward system
starts deep within the brain in an area called the ventral tegmental area and
projects to the nucleus accumbens and then on to upper parts of the brain such
as the cerebral cortex.
Current research
supports the idea that initial exposure to alcohol activates the reward pathway
releasing DA in the Nucleus accumbens, which in turn sends messages to the
cortex to be coded as experiences and perhaps as memories. Once coded, these
experiences can influence, i.e. promote, subsequent behavior such further
alcohol intake. Since these "memories" of drinking are linked to the
environment in which the drinking took place, it is not surprising that the
environmental cues can be important in guiding subsequent drinking
behavior.
Alcohol’s action on the brain produces of a
number of behavioral effects. These effects are dependent upon the 1. amount of
alcohol taken in, 2. the time period over which the alcohol is drunk, 3.
whether other drugs are being taken at the same time, 4. the previous drinking
history of the individual, 5. the physical state of the person doing the
drinking, 6. the genetic background of the individual( i.e. ethnicity, gender),
7. the mood and psychological makeup of the individual and 8. the environment
when alcohol is taken.
1. Amount of alcohol drunk: Generally
small amounts of alcohol [Blood Alcohol Concentrations (BAC) = 0.03 – 0.12%]
produce lowered inhibitions, feelings of relaxation, more self confidence,
diminished judgement, reduced attention span, and slight incoordination. BAC’s
of 0.09 to 0.25% induce more incoordination, slower reaction times, loss of
balance, blurred vision, exaggerated motions, difficulty in remembering. Higher
BACs to 0.3% result in confusion, dizziness, slurred speech, severe
intoxication, alterations in mood including withdrawal, aggression, or
increased affection, and diminished ability to feel pain. Even higher BACs, to
0.4%, can result in stupor, being incapacitated, having loss of feeling,, being
difficult to arouse, and lapses in and out of consciousness. Finally, as the
blood level approaches 0.50% the person may die due to a variety of
physiological complications such as diminished reflexes, slower heart rate,
lower respiration, and decreased body temperature.
2. Time over which the alcohol is drunk:
Rapid intake of alcohol results in more alcohol in the stomach and small
intestine. This produces a larger gradient of alcohol and greater absorption
into the blood stream and thus distribution into the tissues including the
brain. If alcohol is taken in more rapidly than it is metabolized (1/3 oz to
1/4 oz. per hour in an average person), then the BAC continues to rise.
3. Use of other drugs with alcohol: The
utilization of other drugs at the same time that alcohol is being drunk can
result in increased effects of the alcohol. This action can occur several ways
including enhancing the absorption and distribution of alcohol, action on the
same chemical systems in the brain as alcohol, and/or slowing the metabolism of
ethanol through competition at the liver for metabolizing enzymes or even
damage to the liver so it doesn’t work as well.
4. Previous drinking history: The
previous drinking history is influential in determining the effects of current
alcohol consumption. Often times, dependent upon the amount and timing of prior
alcohol consumption, the person will develop a tolerance. Tolerance to alcohol
can be loosely defined as needing alcohol to produce the same effect.
Therefore, a person who has developed tolerance will need more alcohol to
produce some of the same effects. It should be noted that not all systems
underlying behavior develop tolerance at the same rate. In addition to
tolerance, it is probably that after heavy long-term drinking that damage has
been done to the brain and to the liver. In these cases response to alcohol may
be different than that originally seen and/or prolonged since the liver can’t
metabolize the ethanol as rapidly.
5. Physical state: A person’s physical
state can be an important determinant of their response to alcohol. As
mentioned in number four above, if a person has an impaired liver, then the
metabolism of ethanol will be impaired thus enhancing and/or prolonging the
alcohol action. Further, the nutritional status of the person can be an
important determinant of the action. Food in the stomach will compete with
ethanol for absorption into the blood stream. It is well known that alcohol
competes and influences the processing of nutrients in the body. To the extent
that a well nourished body is able to respond to everyday demands of living,
the extend of malnourishment may determine the extent and magnitude to which
the body can respond to alcohol.
6. Genetic background: The genetic
background of an individual is an important determinant in the response to
alcohol. There are several important examples of this. A certain portion of the
Asian population carries modifications of enzymes responsible for the
metabolism of alcohol such that drinking causes these individuals to have
facial flushing and become sick or nauseous. Women are generally more
responsive than men to the same amount of alcohol because of differences in
metabolism and differences in the amount of body water.
Children of alcoholics are much more likely to
become alcoholic, findings that are not a result of environment. Many strains
of animals are more responsive to alcohol than are other strains and animals
have been bred to prefer alcohol, sleep longer after ethanol administration,
and to have more severe withdrawal from alcohol.
7. Mood and psychological makeup: Use of
alcohol tends to potentiate the mood of the user. Thus, if one is sad, alcohol
may make you sadder. If you are happy, alcohol may make you happier. The
psychologically make-up of an individual becomes important since alcohol may
diminish some controls, which keep the person functioning well under usual
circumstances. Loss of those controls may lead to difficulties such as
aggression and other unwanted behaviors.
8. Environment: The environment in which
a person drinks is an important determinant of the effects of alcohol. For
example drinking at a festive party will often cause the person to become more
festive. A good example of this is the behavior of the thousands of people who
attend Mardi Gras in New Orleans each year. This is essentially a huge party
that goes on and on and people’s behavior and energy level is potentiated by
the group. In contrast, it would be expected that drinking at sad occasions
would result in more sadness.
Liver:An association between alcohol consumption
and liver disease has been known for over 200 years (Smart and Mann, 1992). In
fact, the most common cause of illness and death from liver disease is from
long-term alcohol consumption (National Center on Health Statistics, 1994).
Since the liver is the primary site of alcohol metabolism, it is not surprising
that it is particularly susceptible to alcohol-related injury. The injury to
the liver from long-term drinking apparently comes not only from ethanol, but
also from the dangerous products generated upon the metabolism of ethanol.
These include acetaldehyde and highly reactive molecules called free
radicals. (Free radicals are a group of elements or atoms usually passing
intact from one compound to another, therefore in an uncombined from. As free,
it is usually short lived and highly reactive.)
Normal Liver
Since the liver is the largest
organ in the body (approx. 3.3lbs) and one of the most important being involved
in a number of important processes, it has considerable reserves and is able to
regenerate itself. Therefore, limited damage to the liver can go undetected and
the insult needs to be quite substantial in order for damage to occur. With
respect to alcohol, this means drinking large quantities of alcohol over many
years. It has been estimated (Mazey et al., 1988) that in men the dose needed
would be 600 kilograms taken chronically. This is equivalent to 72 oz of beer,
1 liter of wine, or 5 or 6 standard drinks (1.5oz) daily for 20 years. For
women, the amount needed would be one-fourth of this due to gender
differences in the ability to "handle" alcohol.
There are three major
categories of liver damage (French et al, 1993) from alcohol ingestion, which
are usually thought of as a progression in severity, however this is not always
the case. These are:
1. Fatty liver – Fatty liver means fat
disposition in the liver. This can occur after as single drinking session and
after chronic consumption. Fatty liver is reversible and may not lead to more
serious liver problems.
2. Alcoholic hepatitis – "This disorder
is characterized by widespread inflammation and destruction of the liver". The
liver may have scar tissue. The symptoms may include fever, jaundice and
abdominal pain. The condition may be fatal, but may be reversible if one quits
drinking. It occurs in 50% of heavy drinkers.
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. (Dufour et al, 1993). 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 (extracellular
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.
Images below are courtesy Alcohol Health and
Research World, Effects of Alcohol on Organ Function, Vol21, #1, 1997. U.S.
Department of Health and Human Services
Normal Kidney
How does ethyl alcohol act
in the kidney to produce electrolyte Disturbances?
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 (see figure),
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.
Alcohol’s 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.
Effect of Ethyl Alcohol on Electrolytes Problem Major Cause(s)
Low sodium level
(hyponatremia
Massive intake of
solute-free fluid (beer
Low potassium level
(hypokalemia)
Dietary deficiency,
gastric losses, leaky membranes, shifts from extracellular to
intracellular
Low phosphorus level
(hypophosphatemia)
Dietary deficiency,
malabsorption, increased cellular uptake
Low magnesium level
(hypomagnesemia)
Dietary deficiency,
malabsorption, phosphorus deficiency
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 body’s
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.
What accounts for the ability of some to drink without difficulty in contrast to those who become "addicted"?
Definition of Addiction
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.
- A modified reward process
where by drinking of alcohol provides an overall positive effect
(euphoria or decrease in an unpleasant situation). This is coupled in those
vulnerable individuals with a pattern of diminishing or ignoring the negative
impacts of overconsumption - the hangovers, loss of memory, fights, violence
and arrests. The less vulnerable individual equates heavy alcohol consumption
as overall unpleasant as result of the negative effects outweighing the
positive.
- Neuroadaptation where by the
brain attempts to compensate for something (ethanol) which influences normal
functioning.
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 brain’s 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
- facilitates the action of the major depressant
neurotransmitter in the brain (GABA) and
- inhibits the action of the major excitatory
neurotransmitter in the brain (glutamate).
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.
About Alcoholism
from the National Institute of Alcohol Abuse and Alcoholism
(NIAAA)
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.
Reference:
Tenth Special Report to the U.S. Congress on
Alcohol and Health, June 2000. U.S. Department of Health and Human Services,
Public Health Service, National Institutes of Health, National Institute on
Alcohol Abuse and Alcoholism.