The Ins and Outs of Ethanol

Last post for PHYL3004! This post will discuss the favourite drug of many students worldwide- ethanol!

What factors govern absorption of ethanol into the blood stream?

Ethanol is quite water-soluble due to its -OH group. It is also fairly lipid-soluble due to its CH₃CH₂- group. As ethanol is a small, uncharged molecule, it is also able to cross cell membranes and have an effect on the various tissues of our body without requiring any kind of chemical modification.

Ethanol is absorbed into the circulation via passive diffusion. Most (~80%) is absorbed through the small intestine, whereas the remaining 20% is absorbed in the stomach wall. As such, factors governing ethanol absorption are the same as factors governing diffusion in general: concentration gradient, permeability, and surface area. Most ethanol is absorbed in the intestines because the intestines have a much larger surface area than the stomach.

You've probably heard the advice to "never drink on an empty stomach." But why is this? Ethanol is absorbed more slowly after eating. This is because the presence of food in the stomach delays gastric emptying, allowing ethanol to remain in the stomach longer, where it is absorbed at a slower rate. The slower rate of ethanol absorption allows the body more time to metabolise any ethanol that has already been absorbed, which also reduces the peak of blood alcohol concentration.

The distribution of ethanol into various tissues depends on the relative water content of the tissue. Ethanol is both water- and lipid-soluble, as I said earlier, but it is more water-soluble than lipid-soluble. Therefore, it is highly soluble in the blood but has low solubility in fats. Females tend to have a reduced body water compared to males due to increased fat mass and decreased muscle mass (muscle cells have more water than fat cells). Therefore, blood alcohol concentration increases more for females than for males, which is why females are recommended to have fewer drinks than males. Similarly, other populations with reduced muscle mass (e.g. elderly) may also be more susceptible to the effects of alcohol.

What are the determinants of peak blood alcohol concentration?

Blood alcohol concentration is, well, the concentration of alcohol in the blood. It is usually given as a percentage. The legal driving limit in Australia is 0.05%, or 0.05g per 100mL of blood.

I've already hinted at a couple of determinants of peak blood alcohol concentration: stomach fullness and the proportion of fat and muscle. The obvious other determinant of blood alcohol concentration is the number of standard drinks consumed. 1 standard drink is equivalent of 10g of pure alcohol.

Why is the brain susceptible to the effects of ethanol (beginning with the blood-brain barrier)?

Before ethanol gets anywhere near the central nervous system, it already has effects on sensory nerves. Remember how capsaicin stimulates the sensation of heat? Ethanol works through the same pathway, stimulating TRPV1 receptors (i.e. vallinoid receptors, the same receptors stimulated by capsaicin).

Ethanol can cross the blood-brain barrier as it is a small, uncharged molecule. Once in the brain, it causes inhibition by enhancing the activation of inhibitory GABA_A receptors and suppressing the activation of excitatory glutamate receptors. Alcoholics have an adaptive response in which their brain increases its level of excitation. During withdrawal, these compensatory excitatory effects persist long after inhibition by alcohol has ceased, causing withdrawal symptoms.

How is ethanol removed from the body?

Ethanol is not stored- it just hangs around until it gets removed. Most of this removal (~90%) is via metabolism, most of which occurs in the liver. In the liver, alcohol is converted into acetaldehyde by alcohol dehydrogenase (ADH), and acetaldehyde is then converted into acetate via aldehyde dehydrogenase (ALDH). Both of these reactions require NAD+ as a cofactor. As ADH is also expressed in the stomach, a small amount of ethanol is metabolised in the stomach before absorption, reducing the total amount of ethanol absorbed. Interestingly enough, the efficacy of ADH is reduced in alcoholics.

The remaining ~10% of ethanol is excreted unchanged in the urine, breath or sweat. The concentration of ethanol in the blood is the same as in the urine. Urinary clearance is only around 1mL/min, so it's a good thing that we have so many other mechanisms to get rid of alcohol.

Removal of alcohol via the breath is quite unique. While oxygen and carbon dioxide enter the alveoli via the pulmonary circulation, ethanol actually diffuses across the airways from the bronchial circulation. We know this because a graph of breath ethanol concentration shows an exhalation pattern more similar to airway gas exchange than alveolar gas exchange. In alveolar gas exchange, there is an initial plateau (dead space air), a steep increase in concentration (due to transition from dead space air to alveolar air) and a final plateau (alveolar air). In airway gas exchange, like in ethanol, the initial plateau is absent, the steep increase represents the conducting airways, and the plateau phase represents alveolar air that has been modified in the exchange zone. Furthermore, the location of gas exchange appears to depend on the liquid to gas partition ratio, or λ. The blood and water solubility for ethanol (which is exchanged in the airways) is far greater than for oxygen or carbon dioxide (which are absorbed in the alveoli).

In airway exchange of ethanol, ethanol first moves into the airway surface liquid that lines the airways and humidifies inspired gas. Ethanol then moves down the airways during inspiration (as this means that it is moving down its concentration gradient). Movement of ethanol down the airways causes saturation of alveolar air with ethanol, so there is no concentration gradient in the alveoli. Therefore, there is no alveolar exchange of ethanol.

And I think that's it! Good luck in exams!