Wilson disease

One essential mineral that our body needs to get through the diet is copper, and typically we take in about 1 to 2 mg per day from the food we eat, things like whole grains, beans, nuts and potatoes; but really our body only needs about 0.75 mg / day, so that extra copper is excreted.

About 90% of the excess copper is excreted into the bile, where it eventually ends up as fecal copper, and the other 10% is excreted in the urine.

In Wilson disease, there’s genetic defect that results in the excess copper being kept in the body and deposited in various tissues...where it’s not supposed to be, and just like iron, free copper reacts with hydrogen peroxide in the body to form the hydroxyl radical, a reactive oxygen species that’s pretty good at damaging tissue, so over time those tissues are seriously damaged by free radical generation.

Now your liver cells, or hepatocytes, play a really important role in helping the body get rid of excess copper.

So usually the copper from the diet is absorbed in the small intestine via enterocytes, and passed off into the portal vein to the liver.

Once it’s in the liver it’s sent to a special transport protein called ATP7B, which has a couple super important jobs.

The first job, is that it binds copper to apoceruloplasmin, which is the major copper-carrying protein in the blood and is responsible for carrying 95% of the copper in blood.

After it binds copper it’s then just called ceruloplasmin, and this guy can haul 6 molecules of copper at once.

ATP7B’s other job is to gather up the rest of the copper into vesicles to be exocytosed into into the bile canaliculi, where it goes into the bile and is eventually excreted.

With Wilson disease, there’s an autosomal recessive defect in this ATP7B transport protein. As you could probably guess, that means it can’t incorporate the copper into ceruloplasmin or excrete it into the bile.

Since it’s not doing either of these things anymore, the copper builds up inside the hepatocyte and starts to produce free radicals.

Eventually, all this built up copper and free-radical damage injures or destroys the hepatocyte, causing free copper to spill out into the interstitial space and from there into the blood supply, where it’s circulated to and deposited in other tissues, where it also causes free radical damage over time.