How Liver Problems Can Lead to Brain Disease

How Liver Problems Can Lead to Brain Disease


[INTRO ♪ Your brain works together with the rest of
your body in lots of different ways. If things go wrong with some organs, like
if your heart stops pumping, your brain’s obviously going to have a bad
time. But sometimes the connection is a little less
straightforward. Take the liver, for example: you need it for
things like filtering blood, storing vitamins, and lots of other processes
that keep you alive. So, basically, what happens in the liver doesn’t
stay in the liver. And an issue there can cause a chain reaction
across your body that seriously affects your brain. Patients with many kinds of liver damage or
disease can develop a condition called hepatic encephalopathy,
or HE. Hepatic refers to the liver, and encephalopathy
means brain disease, damage, or malfunction. Physicians think of HE as a spectrum of symptoms
that can affect personality, movement, cognition, and even levels of consciousness. They can range from mild, like mood swings,
to severe, like a coma. And HE is mainly caused by substances that
build up when the liver stops working as well as it
should. In a healthy liver, chemicals from the rest
of the body are filtered out of the blood and broken down
by specialized cells and enzymes. If the liver becomes damaged, like from certain
drugs, a bad diet, or some other kind of injury or disease, the
tissue changes structure and gets all scarred. This scar tissue isn’t able to function
like normal liver cells. Plus, all those structural changes make it
harder for blood to get in for detoxification. And in really severe cases, a lot of blood
may bypass the liver entirely. One important toxin your liver deals with
is ammonia, which mostly comes from the digestion of proteins
in your gut. Ammonia gets turned into urea, which is excreted
in pee. So a damaged liver can lead to a buildup of
ammonia in the bloodstream, which is bad news for the brain. Ammonia can cross the blood-brain barrier,
which is a membrane that blocks a lot of molecules in your bloodstream from circulating around your brain, to protect
it from potential damage. Once ammonia slips past, it’s mostly taken
up by astrocytes, which are brain cells that help out neurons
in a lot of different ways. And astrocytes have enzymes that convert ammonia into the amino acid glutamine to help protect
the neurons. If they do this too much, though, studies
have found that their structure gets messed up. Cell-damaging molecules called free radicals
get produced, and their mitochondria stop working as efficiently, which means they can’t make as much energy. As the astrocytes lose function, they stop
getting rid of ammonia, and everything gets even more messed up. Too much ammonia can affect the storage, production, and use of neurotransmitters across the whole
brain. In other words, your neurons can’t really
communicate, which can cause a whole range of problems
with mood, movement … pretty much anything. Even though ammonia is a significant part
of HE, other toxins might be involved too. And researchers are still figuring out exactly
what they are and how they might make HE worse. Besides waste products like ammonia, your
liver also has a huge impact on how long lots of drugs—
from aspirin to LSD— stay in your system before they’re flushed out. A healthy liver takes drug molecules from your
bloodstream and converts them into different chemicals. Sometimes they’re the active form of a drug, but eventually they become more water-soluble
compounds that can be peed out. To do this, it mostly uses a system of enzymes
known as the cytochrome p450 family, which may be responsible for up to 75% of drug metabolism. So if a disease damages liver cells or directly
interferes with these enzymes, things can go sour. Even just as we age naturally, the activity of cytochrome p450 enzymes seems to dip. Slower drug metabolism can mean a normally fine painkiller, like acetaminophen, may build up until it
hits toxic levels. This can lead to more damage, and eventually
we’re right back to hepatic encephalopathy. Now some brain diseases are linked to toxic
substances that some people intentionally put in their
bodies, which their livers have to process—like
ethanol from alcoholic drinks. Basically, in the process of breaking down
ethanol, the byproducts can cause tissue damage and
trigger inflammation. And if your liver keeps getting damaged, it
won’t be able to handle ethanol as well. It’s a vicious cycle. It turns out that too much ethanol can affect
your cells’ ability to take up, store, and use thiamine, also known as vitamin B1, from your diet. Some enzymes that depend on thiamine are a
key part of glycolysis, a process your body uses to break down glucose
molecules and make energy. So a lack of thiamine can limit the amount
of energy your body can get from food. And since the brain is basically an energy-hungry
monster, that is a recipe for disaster. And it can lead to Korsakoff syndrome, one
of the lesser-known diseases that affects memory. Patients find themselves basically frozen
in time, with retrograde and anterograde amnesia. So they can’t recall large chunks of their
past, or form new memories going forward. Specifically, in patients’ MRIs, we’ve
seen shrinking in the medial thalamus, mammillary bodies, and nearby areas—which
are all linked with memory. With treatments aimed at getting thiamine
and other nutrient levels back to normal, many Korsakoff’s patients
can at least partly recover. But, basically, if you want to keep your brain
in tip-top condition, remember to take good care of the rest of
you as well. And take special care of your liver—just a good ol’ … wherever it is. Thanks for watching this episode of SciShow
Psych! If you want to keep learning about the human
brain with us, from questions about behavior to more deep
dives into disease, you can go to youtube.com/scishowpsych to
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