Alcohol-associated liver disease

Alright, so when you drink alcohol, what happens? Well, okay, what happens to the alcohol? Well that’s mainly your liver’s job, right?

Basically, once the alcohol gets to your stomach, most of it’s sent to your liver for processing.

In very small amounts, alcohol is more or less harmless, but in excess, it can lead to serious liver complications, and is the leading cause of liver disease in western nations.

Once in the liver cells or hepatocytes, it can take one of three pathways, one of which involves an enzyme called alcohol dehydrogenase or simply ADH, and this happens in the cytosol of the cell, another involves a catalase inside organelles called peroxisomes, and a third involves being converted by the enzyme cytochrome P450 2E1, sometimes just shortened to CYP2E1.

All three of these pathways lead to the conversion of alcohol to acetaldehyde.

Once the ADH enzyme is used to convert the alcohol, it needs another compound called NAD+, which is then converted into NADH.

As NADH levels increase, and NAD+ levels decrease, this has two effects, higher NADH levels tell the cell to start producing more fatty acids, and lower NAD+ levels result in less fatty acid oxidation, both of which lead to more fat production in the liver.

Now excessive fat in the liver is also known as fatty change or fatty liver, where it gets large, heavy, greasy, and tender, but typically at this point, patients don’t have symptoms like fever or high levels of neutrophils in the blood.

The liver also often takes on a more yellowish color, which is due to all these fat deposits, and we can see that on histology.

All these circles are deposits of fat that contribute to fatty liver disease, and sometimes this buildup of fat in the liver is referred to as steatosis.

Treating fatty liver disease usually involves simply stopping the alcohol consumption.

K so that’s fatty liver, but that’s not the only thing that excessive alcohol consumption can cause, right?

Looking back at our pathways, when you make acetaldehyde from ethanol, you also start to generate these ominous sounding compounds called reactive oxygen species.

You can probably guess that these guys are super reactive and contain oxygen, some examples are like hydrogen peroxide, the hydroxyl radical, or the superoxide anion.

These reactive oxygen species react with different components of the hepatocyte, like proteins and even DNA, and this process can cause serious damage to the cells.

Besides producing reactive oxygen species, now we’ve also got acetaldehyde to worry about.

This compound can bind to macromolecules, enzymes, the cell membrane, and all sorts of other compounds inside the cell.