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.
When they bind to some of these, they effectively inhibit that molecule.
And when that happens, they form what are called acetaldehyde adducts.
And when those are formed, your immune system recognizes these new compounds as foreign
and starts sending neutrophils in to sort of clean up the damage.
So not only do you get these adducts binding to and potentially messing with the function
of certain molecules in the cell, you also get destruction of hepatocytes by the neutrophilic
infiltration.
As cells become inflamed and damaged, patients have developed alcoholic hepatitis, and we
start to note a change on histology and notice these bundles of proteins called Mallory bodies,
specifically these are damaged intermediate filaments and are located in the cytoplasm
of hepatocytes, the mechanism that produces these bodies is still unclear, but they’re
most commonly seen in alcoholic hepatitis.
At this point the patient may have hepatomegaly that’s probably become painful, since the
liver’s seeing more immune cells, they also may have neutrophilic leukocytosis, or an
increased neutrophils in the blood.
Also, as cells become damaged and die off, scar tissue starts to form around the central
veins in the liver, known as perivenular fibrosis.
The damage done to hepatocytes also results in leakage of liver enzymes like alanine aminotransferase
(or ALT) or aspartate aminotransferase (or AST), both types of transaminase, usually
even though both are elevated, AST will be found to be greater than ALT in alcoholic
hepatitis.
In addition to these two, serum alkaline phosphatase (or ALP) and gamma glutamyltransferase (or
GGT) will also be elevated.
In some cases, thrombocytopenia, a deficiency of platelets in the blood as well as possible
hypoglycemia, or low blood sugar, can also be found in blood of someone with alcoholic
liver disease.
Treatment again involves completely stopping alcohol consumption, and in some cases corticosteroids
can help suppress the immune system.
Finally, if allowed to progress far enough, chronic alcohol-induced liver damage may lead
to cirrhosis and liver failure.