AssessmentsAlcohol use disorder
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 56-year-old man with a long history of alcohol use disorder presents to the emergency department with multiple neurological concerns and a history of multiple emergency department visits. He is disoriented and confused. Neurological exam shows a wide, slow unstable gait and he is unable to track movement with his eyes. Review of past medical records shows a 24-pound weight loss from previous visits. Initial management includes fluids, dextrose and vitamin supplementation. Which of the following enzymes is most likely to be functioning abnormally?
Content Reviewers:Rishi Desai, MD, MPH
Alcohol is one of the most widely used psychoactive substances in the world, and has been a part of different cultures for hundreds of years.
Drinking alcohol can have serious harmful consequences, it’s been linked to various cancers, gastrointestinal diseases, and metabolic problems.
Over time, regular use of alcohol can lead to alcohol dependence and bouts of withdrawal, and this can take a serious physical and emotional toll on a person’s life.
Alcoholic drinks contain the chemical ethanol, which is a tiny molecule that reduces the activity of various inhibitory and excitatory neurotransmitter pathways in the brain.
Inhibitory neurotransmitters make neurons in the central nervous system less likely to fire an action potential, and the brain’s major inhibitory neurotransmitter—gamma-aminobutyric acid or GABA—acts as an “off” switch and restricts brain activity.
Ethanol is a GABA agonist, so when it binds to GABA receptors it makes that inhibitory signal even stronger.
Ethanol also activates opioid receptors and induces the release of endogenous morphine—known as endorphins.
The opioids then bind to receptors on dopaminergic neurons in the nucleus accumbens, which trigger the release of dopamine and serotonin in that part of the brain.
Ethanol also acts as a glutamate antagonist.
In other words, ethanol blocks glutamate, which is an excitatory neurotransmitter, from binding to glutamate receptors, making it less likely that those neurons will fire.
The combined effect that ethanol has on these neurotransmitters varies by the location in the brain.
For example, in the nucleus accumbens and the amygdala, which are the reward centers of the brain, ethanol produces pleasant or rewarding feelings like euphoria.
This is important because if a person believes that drinking leads to euphoria, they are more likely to drink again.
In the cerebral cortex, the thought-processing center of the brain, ethanol slows everything down, making it difficult to think and speak clearly.
Ethanol also slows behavioral inhibition centers like the prefrontal cortex, making people feel more relaxed and less self-conscious.
In the cerebellum, the area responsible for movement and balance, ethanol causes individuals to lose their coordination, making it harder to walk or do complex tasks like driving.
Ethanol also affects the hypothalamus and pituitary glands, which regulate various hormones and mood.
In these areas, ethanol typically increases sexual arousal, but decreases a person’s ability to engage in sex.
In the medulla, which controls automatic functions like breathing, consciousness, and body temperature, ethanol increases sleepiness, slows breathing, and lowers the body temperature to a point where it’s life-threatening.
Alcoholic drinks have varying amounts of ethanol.
For example, 355 ml or 12 fluid ounces of beer typically contains 5% ethanol by volume, 148 ml or 5 fluid ounces of wine has 12% ethanol by volume, and 44 ml or 1.5 fluid ounces of 80-proof distilled spirits like gin, rum, tequila, or whiskey contains 40% ethanol by volume, all three of these alcoholic drinks therefore have about 18 ml of pure ethanol.
Ethanol’s effects on a person are directly related to the blood alcohol content, or BAC, which is the percentage of ethanol in a given volume of blood.
BAC is affected by the amount of ethanol consumed as well as a person’s blood volume, which depends on their size and sex, as well as situational factors like how much they’ve had to eat or drink, what other substances or medications they may be using, and how well the body is prepared for the alcohol.
At a blood alcohol content of 0.0 to 0.05%, people typically feel relaxed and happy, but might have slurred speech, and some difficulty with coordination and balance.
At a blood alcohol content of 0.06 to 0.15%, there is more impairment in speech, memory, attention, and coordination, and some individuals can get aggressive and even violent.
Complex tasks like driving can become dangerous, which is why it is illegal to drive in some countries with a blood alcohol content of 0.08% or higher.
At a blood alcohol content of 0.16 to 0.30% individuals can experience alcohol poisoning with blackouts or periods of amnesia, vomiting, or even a loss of consciousness.
Finally, at a blood alcohol content above 0.31%, the effect of alcohol can severely suppress breathing and even lead to death.
Over time, individuals who consistently use alcohol can develop tolerance to its effects.
This means that with repeated use, they have a reduced response to alcohol, and therefore an increased dose is needed to achieve the original response.
At a cellular level, there are a couple theories that explain why this might happen.
One is that repeated exposure to ethanol may cause GABA, glutamate, dopamine, and serotonin receptors to become less sensitive to alcohol.
Another is that neurons may remove these receptors from the cell wall in a process called down-regulation, leaving fewer receptors available for binding.
In either scenario, tolerance leads to the need for higher and higher doses of alcohol, and often times that tolerance stays for a long time even after decreasing alcohol use.
Now, let’s say that you’re at rest, without alcohol or anything stimulating your reward pathway.
In this situation, your brain keeps your heart rate, blood pressure, and wakefulness in a normal state, called homeostasis.
Now, let’s say that your secret crush sends you a text.
All of a sudden you may feel sweaty and flushed, your heart rate may jump a bit.
You’re now above your normal level of homeostasis, because something has changed, right?
But it doesn’t stay that way for long, and after the text, your brain brings things back down to this baseline.
With repeated alcohol use, a few things start to happen.
Let’s say you drink at a specific time and setting, like 5pm in the kitchen, and, being a depressant, it makes everything go slower, including heart rate, blood pressure, and wakefulness.
Your brain, being the smart brain that it is, will pick up on that pattern for next time.
Now, next time, at 5pm in the kitchen, the brain preemptively increases functioning, since it knows that when you drink the alcohol, everything’s going to decrease.
Now, let’s say 5pm in the kitchen rolls around, but there’s no alcohol.
In that situation, the brain still increases heart rate and blood pressure, but the changes aren’t countered with the effects of alcohol, and so the person can feel awful, and these are called withdrawal symptoms.