copper disease question

[lasek]

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i just had an exam (not boards) a few days back, and there was a question about which disease has increased copper. i dont remember the exact question or answers but a partial list of the answers was a: gauchers disease, b: alpha-1-antitrypsin defifciency, and several liver diseases. wilson's dz was not listed, and neither was copper ingestion in any shape or form. i cant find anything in robbins, emedicine, uptodate, school notes or google. does anyone know which other diseases are there in which there is increased copper? its just bugging me that i cant find the answer.

 

[Ramoray]

any liver disease could interfere with excretion of copper into bile which is the main excretory path. I would guess one of the liver diseases listed that also caused bile flow problems would also probably lead to some copper excess since it could not be excreted in bile. sorry do not know a specific disease however

 

[primadonna22274]

I think it's Wilson's disease. You measure ceruloplasmin level.
How many points do I get if I'm right? Just pulled that out of some neurofibrillary tangle somewhere....
Lisa PA-C

any liver disease could interfere with excretion of copper into bile which is the main excretory path. I would guess one of the liver diseases listed that also caused bile flow problems would also probably lead to some copper excess since it could not be excreted in bile. sorry do not know a specific disease however

 

[JackBauERfan]

i just had an exam (not boards) a few days back, and there was a question about which disease has increased copper. i dont remember the exact question or answers but a partial list of the answers was a: gauchers disease, b: alpha-1-antitrypsin defifciency, and several liver diseases. wilson's dz was not listed, and neither was copper ingestion in any shape or form. i cant find anything in robbins, emedicine, uptodate, school notes or google. does anyone know which other diseases are there in which there is increased copper? its just bugging me that i cant find the answer.

Primary Sclerosing Cholangitis gets it, worse as the disease gets worse

 

[JackBauERfan]

he said not wilson's disease...i think i win , yay what do i get!

yeay, just found it on uptodate.

 

[Ramoray]

he said not wilson's disease...i think i win , yay what do i get!

yeay, just found it on uptodate.

it would be anything that blocks bile flow. could be a number of those diseases. I wouldnt say you win think outside the box son

 

[JackBauERfan]

yeah but i'm just saying, it could by ANYTHING that does that, but obviously they wanted one of the liver ones on the test. and my bet is it was psc. but who cares, i dont really win anything haha.

 

[JackBauERfan]

yeah but i'm just saying, it could by ANYTHING that does that, but obviously they wanted one of the liver ones on the test. and my bet is it was psc. but who cares, i dont really win anything haha.

and you have to know whats inside the box before you start thinking outside of it, haha, so i still have some time to go 🙂

 

[lasek]

Thank you rohitpatel and ramoray. I think PSC was one of the answers, as was alos primary billiary cirrhosis. I just checked it in a GI and liver disease book (Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease), which actually mentions both diseases have increased copper. Funny how they forgot to mention anything about copper metabolism during lecture.

Ramoray, if I understood you correctly, most liver diseases, and especially those that block bile flow, can (at least theoretically) cause increased serum copper?

 

[Ramoray]

Thank you rohitpatel and ramoray. I think PSC was one of the answers, as was alos primary billiary cirrhosis. I just checked it in a GI and liver disease book (Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease), which actually mentions both diseases have increased copper. Funny how they forgot to mention anything about copper metabolism during lecture.

Ramoray, if I understood you correctly, most liver diseases, and especially those that block bile flow, can (at least theoretically) cause increased serum copper?

I believe that to be the case since copper is exclusively excreted via bile so if bile cant get out copper will build. With a healthy liver though the liver should be able to acccomodate the increase copper by increasing ceruplasmin production and no harm should occur. But i would think the disease with cholestasis and liver damage would cause more problems since copper would accumulate and the damaged liver would not be able to keep pace in accomodating it. So in yoru 2 choices, the primary biliary cirrhoisis would be my guess since it not only blocks bile outflow but causes severe hepatic injury/fibrosis which means loss of liver function which would not be able to accomodate the retained copper.
Compared to PSC which would retain copper but does not damage the liver nearly as badly as prim. biliary cirrosis, therefore liver function is near normal and would bundle all the excess copper into ceruplasmin and you wouldnt see any copper problems
Long story short, i would have chose Prim. Bil Cir.

 

[Idiopathic]

Must remember that in wilsons copper is normal, but the copper-carrier (ceruloplasmin) is decreased, so free copper is higher.

 

[lasek]

I believe that to be the case since copper is exclusively excreted via bile so if bile cant get out copper will build. With a healthy liver though the liver should be able to acccomodate the increase copper by increasing ceruplasmin production and no harm should occur. But i would think the disease with cholestasis and liver damage would cause more problems since copper would accumulate and the damaged liver would not be able to keep pace in accomodating it. So in yoru 2 choices, the primary biliary cirrhoisis would be my guess since it not only blocks bile outflow but causes severe hepatic injury/fibrosis which means loss of liver function which would not be able to accomodate the retained copper.
Compared to PSC which would retain copper but does not damage the liver nearly as badly as prim. biliary cirrosis, therefore liver function is near normal and would bundle all the excess copper into ceruplasmin and you wouldnt see any copper problems
Long story short, i would have chose Prim. Bil Cir.

So to make the long story even shorter, the more damage to liver/billiary tree, the more copper becomes a problem. Similar story as with just about everything else.
Thanks

 

[Ramoray]

Must remember that in wilsons copper is normal, but the copper-carrier (ceruloplasmin) is decreased, so free copper is higher.

This is actually untrue. Wilsons is a problem with the transporter protein involved in getting copper into bile. Therefore Copper levels in the liver increase. The increased copper damages liver function and also impairs incorporation into apoceruplasmin to make ceruplasmin. Ceruplasmin is a combo of apoceruplasmin plus copper, therefore you do not intrinsicallly have a low level of ceruplasmin, but instead you have a low level because copper is not being put into apoceruplasmin due to liver dysfunction.

therefore no ceruplasmin is made and that is why you have decreased levels. Copper levels in the BLOOD are low/normal since the only way you see copper in blood is through ceruplasmin, and since the liver is not putting copper into apoceruplasmin, not as much ceruplasmin is being exported so you have low levels of blood copper.
basically you have a positive high level of copper in the body, especially liver but a misleading low serum copper and ceruplasmin level

 

[Idiopathic]

This is actually untrue. Wilsons is a problem with the transporter protein involved in getting copper into bile. Therefore Copper levels in the liver increase. The increased copper damages liver function and also impairs incorporation into apoceruplasmin to make ceruplasmin. Ceruplasmin is a combo of apoceruplasmin plus copper, therefore you do not intrinsicallly have a low level of ceruplasmin, but instead you have a low level because copper is not being put into apoceruplasmin due to liver dysfunction.

therefore no ceruplasmin is made and that is why you have decreased levels. Copper levels in the BLOOD are low/normal since the only way you see copper in blood is through ceruplasmin, and since the liver is not putting copper into apoceruplasmin, not as much ceruplasmin is being exported so you have low levels of blood copper.
basically you have a positive high level of copper in the body, especially liver but a misleading low serum copper and ceruplasmin level

Im sorry, I should have said serum copper. Total body copper is increased and deposits in the eye, cortex and liver (to name a few), but the thing that often confuses people is what the serum copper is doing (i.e. they expect it to be high).

Thanks for the correction.

 

[Ramoray]

So to make the long story even shorter, the more damage to liver/billiary tree, the more copper becomes a problem. Similar story as with just about everything else.
Thanks

ha true, when it doubt choose the disease that causes the most damage, atleast taht is my strategy when i am not sure.

 

[chak_de_phatee]

basically you have a positive high level of copper in the body, especially liver but a misleading low serum copper and ceruplasmin level

Actually I dont think this is right. My understanding of it is yes the (ceruplasmin+cu) complexed cu is low in serum but the free cu ion fraction is ELEVATED in symptomatic patients. This free cu ion is what deposits in the eye and other tissues and is why we use penicillamine to decrease FREE cu ion level.

 

[Ramoray]

Actually I dont think this is right. My understanding of it is yes the (ceruplasmin+cu) complexed cu is low in serum but the free cu ion fraction is ELEVATED in symptomatic patients. This free cu ion is what deposits in the eye and other tissues and is why we use penicillamine to decrease FREE cu ion level.

nope, look it up in uptodate, cecil, harrisons, emedicine, robbins etc. youll find your mistaken

 

[chak_de_phatee]

nope, look it up in uptodate, cecil, harrisons, emedicine, robbins etc. youll find your mistaken

You might be right.............my only intention is to learn material and help other people when I can..........this is no ego trip. Just wanted to make that clear.



Robbins and emedicine is a little vague on the free fraction of Cu ion. According to Goljan and emedicine it seems that the free ion is elevated.



Emedicine(http://www.emedicine.com/med/topic2413.htm)

Staging: The natural history of the disease may be considered in 4 stages, as follows:

Stage I - The initial period of accumulation of copper by hepatic binding sites
Stage II - The acute redistribution of copper within the liver and its release
into the circulation
Stage III - The chronic accumulation of copper in the brain and other
extrahepatic tissue, with progressive and eventually fatal disease
Stage IV - The achievement of copper balance with chronic chelation therapy




If the free fraction is not elevated then.....

How do you explain the pathogenesis of Kayser-Fleischer rings?

Why is penicillamine considered a treatment if not to chelate the ion?




I do not have access to the other two books yet but will soon but it would be nice to learn this.(If you know the pathogenesis explain it)

 

[Ramoray]

As i have understood the disease and evaluation the serum Copper is variable and that is why its not used in assesment. You use decrease ceruplasmin and the other symptoms to come to a diagnosis. I was saying in a "classic" exmaple that followed everything perfectly you would have a low serum copper as i explained. You DO have a higher overall copper content in tissues like liver and the eye rings you mentioned. All i am saying is that SERUM copper is supposedly low since you dont have its carrier protien available to take in in serum. You are right i do not know the exact pathophys of why copepr can get to teh eye but taht is what im saying, serum copper can be high, normal or low, it varies for what i have read uknown reasons. Also the reason you give chelators is to decrease whatever copper IS floating around. Just cause its normal in the serum, if you have an overload in tissues, even a "normal" serum level is bad since you are already high in all tissues so you want to get anything copper out of there. You are right there is alot that doesnt make sense. Atleast what i am going to know for board wise is you see decrease ceruplasmin, increased liver copper and variable serum copper levels, and whatever other sytmopms.. ie. eye rings. That should be more than enough to diagnose the condition. If you find out more on serum copper loevels please post as i would be interested in learning more. thanks for the reply