We're going to our second metabolic disease of the liver: And this is Wilson's disease.
As soon as you hear Wilson's, close your eyes, your telling me what element?
Copper. Copper. Copper. That is where you begin.
Hemochromatosis, what is your element? Iron. Iron. Iron Pathology.
Wilson - the copper is causing damage, once again from head and down to you liver.
If copper accumulates in the basal ganglia, what does it look like? And what's your walk? Shuffling gait.
What about your flexion of the elbow? Cogwheel rigidity. What is all this?
This is a sign of often awful lot like your Parkinson's.
But it is not Parkinson's It is Parkinson-like right?
Be careful, so the copper here is accumulating at the basal ganglia giving symptoms in your patient of Parkinsonism.
Next, I'll show you the iris; the copper accumulating in the iris.
That is know as Kayser-Fleischer ring.
What's the topic here? Liver disease.
The copper accumulating in your liver’s causing death to your liver.
Let's talk about pathogenesis, it's important Autosomal recessive; excessive accumulation of what kind of copper?
What do you mean what kind of copper Dr. Raj? Copper is copper. No.
In the body, they're either bound or free.
Which faction of copper is elevated?
What is this copper accumulating on the basal ganglia, and the iris, and the liver and so forth? Free copper. Why?
The liver is missing the binding protein for copper.
Do you remember the name of that is? We will see.
Presents under the age of 40, you're right.
I know you are.
But let's just make sure you know, we have the full picture first.
Age, about 40, young, hemolytic anemia, jaundice, elevated ALT, or fulminant liver, neurological symptoms.
There you have it, free copper accumulating in different places.
Neurologic, I talked about Parkinson-like liver disease unfortunately, death to the liver.
The patient might have issues with hemolytic anemia and jaundice as well.
I show you a picture of Kayser-Fleischer in which, you have free copper accumulating in the descemet membrane of the cornea.
It is nearly 100% sensitive in present of neurologic symptoms.
Okay just before we moved one though, I know it's killing you.
In terms of what this being deficient from the liver in Wilson's disease,
what does copper bind to? Ceruloplasmine.
That's your pathology in Wilson's disease.
Let's take a look.
Kayser-Fleischer In the iris, the areas that you are seeing that are brown,
are the areas and in the iris that is accumulation of copper- Kayser-Fleischer.
This patient had Parkinson's -like symptoms.
No doubt, this patient had Wilson’s.
When kind of free copper did you find in the serum? Increased. Increased. Increased.
I'm going to walk you through step-by-step by step of the labs that are important for you with Wilson's.
But your diagnosis would come mostly just by paying attention to your patient.
Let’s now walk you through your laboratory tests.
Pathogenesis and diagnosis of Wilson's disease If the liver fails to synthesize Ceruloplasmine,
Would you be able to tell me The concept of total? Total means free plus bound.
What does Ceruloplasmine mean to you? Bound.
What faction or component of your total makes mostly your total? Free or the bound?
The bound, the bound, the bound, determines the total.
Okay, with all that in mind that we’ve walked through plenty of times.
If you are low in Ceruloplasmine and you know that it is bound form.
Then what are your bound levels is in Wilson’s? Bound copper is decreased. Clear?
If your bound is decreased and you know that it is the major constituent, of total, then what's your total?
Decreased. Keep going.
If you're bound is decreased and your total is decreased, what has to be elevated? The free.
So Doctor why is the total increased if the free is total?
I just told you, that if thinking total, the boundaries the major constituent.
So, you will have increase in free, no doubt.
That free copper then accumulates like and what we have talked about Kayser-Fleischer Basal ganglia, so therefore Parkinson -like.
Here, obviously there's going to be liver damage and then where will you find this free copper? In the urine.
Excretion in the urine; free copper.
Liver biopsy with high free copper content.
What about your ceruloplasmine? Low.
What about the bound? Low.
What about the total? Low.
Management. What do you want to do? Penicillamine is the drug that you should be thinking.
It is a chelator. You need to remove the copper.
Remember hemochromatosis? What were you doing? By week by week phlebotomy, phlebotomy, phlebotomy.
So that you can then remove the iron.
Zinc is used for maintenance.
Worst case scenario: once the liver has been dead, unfortunately, liver transplantation.
One would think that the number of times you've see liver transplantation, that’s it's easy to find a liver, you know that's not true.
All siblings should be screened because this is a genetic issue.