Drug misuse, intoxication and withdrawal: Alcohol: Pathology review

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Case study0:00–1:11

Two individuals are brought into the emergency department, one night. One is 28 year old Brian who was brought in by his friend with complaints of altered consciousness and vomiting.
The friend recalls that Brian had a habit of binge drinking on weekends. On examination, he was disoriented, and had slurring of speech, loss of coordination, and nystagmus.
The second is 2 year old Michelle who’s brought by the mother who reported a seizure episode an hour ago. Upon further questioning, the mother reveals that Michelle was born 2 months prematurely, was always crying and irritable, and was slow in reaching developmental milestones.
On examination, Michelle has reduced height and weight, a small eye opening, smooth philtrum, and thin lips. A neurological exam shows reduced muscle tone and coordination.
When you obtain a more focused history regarding the mother's pregnancy, she reported drinking 3-5 glasses of wine each night during the 1st and 2nd trimester.Okay, both Brian and Michelle’s symptoms are due to alcohol.

Pathology1:11–3:42

Alcoholic drinks contain the chemical ethanol, which mainly acts in two ways in the brain, one, it acts as an agonist to GABA, which is the brain’s major inhibitory neurotransmitter; and two, it acts as an antagonist of glutamate, which is an excitatory neurotransmitter.
Both these actions produce an overall inhibitory action on the brain’s neuronal circuits. Now, ethanol’s effects vary based on the blood alcohol concentration, or BAC, which is the percentage of ethanol in a given volume of blood.
At a blood alcohol concentration of 0.0 to 0.05%, ethanol produces a relaxed and happy feeling, along with slurred speech and some difficulty with coordination and balance.
At a blood alcohol concentration of 0.06 to 0.15%, there is increased impairment to 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 concentration of 0.08% or higher.
At a blood alcohol concentration of 0.16 to 0.30%, individuals can experience alcohol poisoning where they blackout or experience periods of amnesia.
Finally, at a blood alcohol concentration above 0.31%, the effect of alcohol can severely suppress breathing and even lead to death.Now, the use of alcohol can be assessed by direct and indirect tests.
Direct tests measure the alcohol content in bodily fluids like blood, urine, saliva and the air breathed out. In contrast, the indirect tests assess the effect of alcohol on organs like the liver.
Cellular damage causes the release of liver enzymes into the blood.Gamma-glutamyltransferase, or GGT, is the most sensitive indicator of alcohol use.
In addition, aspartate aminotransferase or AST, alanine aminotransferase or ALT, are also elevated in chronic alcohol use, although AST values rise to about twice as much as ALT.
This is because alcohol use decreases ALT activity in the liver. And, that’s high yield!
Over time, in people with prolonged alcohol consumption, neurons adapt by decreasing their number of GABA receptors, while increasing the number of NMDA glutamate receptors.

Alcohol use disorder3:42–6:51

These individuals develop tolerance to the effects of alcohol, and therefore an increased dose is needed to achieve the original response.
Moreover, if the individual suddenly stops drinking, this receptor imbalance leads to overactivity of the central nervous system, which can result in withdrawal symptoms.
Eventually, the individual ends up requiring large amounts of alcohol just to function normally, which is known as alcohol use disorder, or alcoholism.In the long run, alcohol use disorder can have a very deleterious effect on the body leading to several health problems.
It can cause inflammatory changes in the liver leading to steatohepatitis and cirrhosis. Similarly, the pancreas can also be affected, resulting in pancreatitis.
There can also be inflammation of the gastrointestinal mucosa resulting in esophagitis, gastritis, and gastric ulcers. Now, it’s common to see vitamin deficiencies, especially that of B vitamins.
This is due to a combination of decreased synthesis, absorption and storage as well as having poor eating habits. Lack of vitamin B1, or thiamine, can lead to problems like Wernicke–Korsakoff syndrome which presents with ophthalmoplegia, ataxia, and altered mental status, severe and permanent memory impairment; confabulation, which is when the person creates stories to fill in the gaps in their memory which they believe to be true; and personality changes like apathy or indifference.
Another disease caused by thiamine deficiency is Beriberi. There’s “wet” Beriberi where the heart is the most affected, which leads to heart failure.
Common symptoms include lower limb edema and shortness of breath. In dry Beriberi the nervous system, especially the peripheral nervous system, is most affected.
The main symptoms include pain or loss of sensation in the limbs, weakness, decreased tendon reflexes, and muscle weakness.
There could also be confusion and speech difficulties. Thiamine deficiency is treated with intravenous thiamine supplementation foÍllowed by glucose infusion once thiamine levels normalize.
Chronic alcohol use is also associated with an increased risk of high blood pressure, dysregulated lipid metabolism, myocardial infarction, and cerebrovascular disease.
Alcoholism is associated with the risk of developing certain cancers, including mouth, esophagus, throat, liver, and breast cancer.

Fetal alcohol syndrome 6:51–7:54

Now, consuming alcohol during pregnancy can result in ethanol, and toxic alcohol metabolites like acetaldehyde pass freely through the placenta and buildup in the fetus, interfering with the growth and development of various tissues.
The end result is known as fetal alcohol syndrome or FAS. For your exams, remember that this can present with growth retardation during the prenatal and postnatal period, resulting in low height and weight; along with typical dysmorphic facial features like short palpebral fissures, smooth philtrum, and thin vermillion border.
There may also be microcephaly and damage to the brain, including deficits in the corpus callosum, cerebellum, and basal ganglia leading to abnormal reflexes, tone, coordination, intellectual disabilities, and seizures.
Additional features include limb dislocation and heart defects.Now, individuals with alcohol use disorder can present with alcohol withdrawal symptoms when they abruptly stop drinking.

Alcohol withdrawal7:54–9:39

The first withdrawal symptoms to appear include mild tremors, vomiting, anxiety, tachycardia, sweating, and insomnia that occur anywhere between 3 to 36 hours after the last drink.
If left untreated, the individual can progress to more severe symptoms, including withdrawal seizures which are generalized tonic-clonic seizures that occur around 6 hours to 48 hours after the last drink.
Severe withdrawal may additionally present with transient hallucinations or illusions, which are most often visual, that occur 12 to 96 hours after the last drink.
One of the most severe manifestations of alcohol withdrawal is delirium tremens, which typically occurs 2 to 4 days after the last drink.
Delirium tremens characteristically presents with delirium, which is a state of altered mental status that can lead to confusion, anxiety, and even hallucinations.
It is also associated with nausea, seizures, tremors, psychomotor agitation, and autonomic hyperactivity, or overactivity of the autonomic nervous system, typically manifesting as hypertension, tachycardia, and diaphoresis.
Finally, if left untreated, delirium tremens can lead to seizures and even death. A high yield fact to remember is that delirium tremens is classically uncovered in a person hospitalized for a different cause and thus doesn’t have access to alcohol.Now, the treatment of alcohol withdrawal is aimed at managing the withdrawal symptoms, preventing the progression to more severe manifestations like seizures, delirium tremens, and death, treating the addiction.

Treatment of alcohol withdrawal9:39–11:41

Mild withdrawal usually requires only supportive care, which includes placing the person in a quiet and warm environment and placing them in the recovery position.
That’s where the body is placed facing downwards and slightly to the side, supported by the bent limbs, and where the chin is well up to keep the epiglottis open and to prevent individuals from vomiting and aspirating their vomit.
Individuals at risk for severe withdrawal should be hospitalized.Risk factors include a recent drinking history, frequent alcohol consumption, a past history of severe withdrawal, seizures, hallucinosis, or delirium tremens, or a history of other depressant use like benzodiazepines or barbiturates.
Typically, all individuals going through a withdrawal are given the vitamin thiamine to prevent seizures and Wernicke’s encephalopathy, because people who consume alcohol also tend to have poor diets that lack thiamine.
In addition, benzodiazepines, like\, lorazepam,diazepam, or chlordiazepoxide, which act as central nervous system depressants can be used to simulate the effect of alcohol by depressing the brain.
These medications prevent the development of severe withdrawal symptoms like delirium tremens and also have the added effect of sedating agitated, violent, and uncooperative individuals.
Usually, a short course of chlordiazepoxide is given and gradually weaned off. Once a delirium sets in, similar treatment protocols are followed but with higher medication doses.Once the withdrawal phase has been managed, the focus is shifted to treating the alcohol use disorder.

Treatment of alcohol use disorder11:41–13:43

This is usually achieved by a combination of individual therapy, group therapy, and medication. Individual therapy, like cognitive behavioral therapy, aims to understand the motive behind the individual’s wish to quit alcohol, identify specific barriers to treatment, educate them on withdrawal, and discuss the thoughts, feelings, and behaviors that lead to alcohol use and create a plan to navigate triggers for use.
Whereas group therapies, like peer-support programs, can help individuals commit to ending the use of alcohol and provide a space to hold each other accountable and build up their support groups.
For your exams, also remember that some medications can be used as an add-on to therapy in alcohol dependence, which includes acamprosate, disulfiram, and naltrexone.
Acamprosate can be administered immediately following acute withdrawal. It reestablishes some of the GABA and glutamate pathways that are disrupted by alcohol and reduces neuronal hyperactivity.
Disulfiram is an inhibitor of the enzyme acetaldehyde dehydrogenase, which breaks down acetaldehyde, which is a byproduct of alcohol metabolism.
As a result, acetaldehyde builds up and causes symptoms like nausea, vomiting, headache, flushing, and other unpleasant effects immediately after alcohol is consumed.
This decreases the likelihood that a person will drink alcohol again. Naltrexone is a mu-opioid receptor antagonist that blunts the euphoric effects of alcohol and feelings of intoxication.
This can help reduce the craving so that the individual stays motivated to continue treatment and avoid relapse. All right, as a quick recap...

Review13:43–15:13

Alcohol is a depressant that can cause addiction and dependence. Intoxication can produce a happy feeling, slurred speech, and loss of coordination, impaired speech, memory, and attention, and progress to more serious symptoms like aggressive behavior, amnesia, vomiting, unconsciousness, respiratory depression and death.
Long-term complications of alcohol use include steatohepatitis and cirrhosis of the liver, pancreatitis, gastritis and gastric ulcers.
In addition, there can be a deficiency of B vitamins, most commonly thiamine, leading to Wernicke–Korsakoff syndrome; high blood pressure, myocardial infarction, cerebrovascular disease, and increased risk of cancers.
Moreover, alcohol consumption during pregnancy results in fetal alcohol syndrome. Now, alcohol withdrawal can cause mild tremors, vomiting, anxiety, tachycardia, sweating, and insomnia within 3 to 36 hours after the last drink; generalized tonic-clonic seizures 6 hours to 48 hours after the last drink; transient hallucinations 12 to 96 hours after the last drink; and finally, delirium tremens 2 to 4 days after the last drink.

Summary15:13–16:01

Okay, back to our cases! 28 year old Brian is brought in with complaints of altered consciousness and vomiting.
Along with the binge drinking habit and examination findings of disorientation, slurring of speech, loss of coordination, and nystagmus should help you arrive at a diagnosis of alcohol intoxication.
Next, 2 year old Michelle has had an episode of seizure and has a history of premature birth, crying, irritability, and delayed developmental milestones.
Added examination findings of reduced height and weight, small eye opening, smooth philtrum, and thin lips, reduced muscle tone and coordination, should make you suspect fetal alcohol syndrome.
And, the history of alcohol use in pregnancy should confirm the diagnosis of fetal alcohol syndrome.
Drug misuse, intoxication and withdrawal: Alcohol | Osmosis