Elevated bilirubin/cholestasis (bloods)

[Stewie]

Gilbert's disease is a benign diagnosis which usually manifests in adults after 24-36 hours of fasting as jaundice and mild-to-moderate unconjugated hyperbilirubinemia and all other lab values being unremarkable.

Hey PB! Your posts are always insightful and very informative, thank you!

If I ever choose to venture back-down the path towards being a PA again, you as well as a few other members here that I know that are physicians, I'd definitely be scratching your minds when I'm prepping for PANCE.

Nonetheless, in the opening post by the OP, he pointed out he was diagnosed with cholestasis. So I just drifted past that posts as there's not much that I can offer. Outside it was just stay hydrated and limit your junk food-high fat foods. Maybe throw in a few shots of some strong tequila! That'll clear that bile backup! ...just kidding, don't do that.

As for the Dx of the OP, D-I cholestasis, yay, nay or somewhere in between?

 

[Stewie]

If it's plain simple cholestasis, then what's causing it?

I would say probably not so healthy diet and possibly the tamoxifen?

 

[blkhrt_jordan]

And that's our first Daily Double today, Stewie. Now for $500 worth of Bitcoin, pay careful attention to the following clue:


These two hepatic enzyme substrate systems are responsible for most of the biochemical detoxification of both endogenous and exogenous compounds in the average adult human body.

Cyp and

Glucuronidation

I can pm u btc addy

 

[Stewie]

And that's our first Daily Double today, Stewie. Now for $500 worth of Bitcoin, pay careful attention to the following clue:


These two hepatic enzyme substrate systems are responsible for most of the biochemical detoxification of both endogenous and exogenous compounds in the average adult human body.

What phases are we specifically asking? And are we asking which group: oxygenated heme coenzyme group or flavin adenine dinucleotide coenzyme group?

If there's chronic up-regulation of interleukin-6 this will slame the breaks on one of the main proteins involved in hepatic detoxification --cytochrome P450 as a whole. Meaning all the CYP isotypes are funked. For the cancer cure conspiracy doughheads. In the face of cancer, the cytochrome family in-which a vast majority of drugs are metabolized is now totally screwed because of this up-regulation of interleukin-6 that shuts down the metabolizing effects of these enzymes. But it's easier to say big pharma has a cure for cancer but they don't want to treat it

We must not forget several other renal and hepatic detoxification pathways such as, Organic Anion Transporter along with Organic Cation Transporter and their paired types. Which I've spoke on these OTC drug transporters interactions with commonly used drugs here such as metformin and berberine.

 

[Stewie]

What phases are we specifically asking? And are we asking which group: oxygenated heme coenzyme group or flavin adenine dinucleotide coenzyme group?

If there's chronic up-regulation of interleukin-6 this will slame the breaks on one of the main proteins involved in hepatic detoxification --cytochrome P450 as a whole. Meaning all the CYP isotypes are funked. For the cancer cure conspiracy doughheads. In the face of cancer, the cytochrome family in-which a vast majority of drugs are metabolized is now totally screwed because of this up-regulation of interleukin-6 that shuts down the metabolizing effects of these enzymes. But it's easier to say big pharma has a cure for cancer but they don't want to treat it

We must not forget several other renal and hepatic detoxification pathways such as, Organic Anion Transporter along with Organic Cation Transporter and their paired types. Which I've spoke on these OCT drug transporters interactions with commonly used drugs here such as metformin and berberine.

Corrected.

 

[MyNameIsJeff]

I would say probably not so healthy diet and possibly the tamoxifen?

The timing doesn't make sense though. Days after beginning the SERMs, itching ensued and elevated ALT, AST and Bilirubin were observed. Not enough time for the SERMs to be causing that. Also, why would Bilirubin continue to climb until the time the second blood work was taken if it was just drug-induced cholestasis? Despite removing the potentially offending agents and the use of TUDCA which has been shown to decrease bilirubin levels acutely in the presence of cholestasis?


"About 2 weeks ago I was just starting day 1 of my PCT of 40/30/20mg nolva 100/50/50mg clomid when the digestive issues came back followed with massive itching all over my body.

Got some bloodwork done, turns out my bilirubin was elevated and I have cholestasis. Subsequently for past 1.5 weeks I've been taking 2g/day TUDCA and 1.5g/day NAC, and cholestyramine as needed. My liver enzymes have dropped (AST 113->77 and ALT 222->140) but bilirubin continues to climb (3.6->4.6). "

Therulersback, get well soon, and please keep us updated on your doctor's diagnosis, a very interesting case.

 

[Pissbrainiac259]

Hey PB! Your posts are always insightful and very informative, thank you!

If I ever choose to venture back-down the path towards being a PA again, you as well as a few other members here that I know that are physicians, I'd definitely be scratching your minds when I'm prepping for PANCE.

As for the Dx of the OP, D-I cholestasis, yay, nay or somewhere in between?

Your Honor,

On advice of legal counsel, let it be clearly stated for the record that notwithstanding any posited evidentiary support, I have never made such claims in any spoken or written language pertaining to the aforementioned post. That is all.

 

[Pissbrainiac259]

What phases are we specifically asking? And are we asking which group: oxygenated heme coenzyme group or flavin adenine dinucleotide coenzyme group?

If there's chronic up-regulation of interleukin-6 this will slame the breaks on one of the main proteins involved in hepatic detoxification --cytochrome P450 as a whole. Meaning all the CYP isotypes are funked. For the cancer cure conspiracy doughheads. In the face of cancer, the cytochrome family in-which a vast majority of drugs are metabolized is now totally screwed because of this up-regulation of interleukin-6 that shuts down the metabolizing effects of these enzymes. But it's easier to say big pharma has a cure for cancer but they don't want to treat it

We must not forget several other renal and hepatic detoxification pathways such as, Organic Anion Transporter along with Organic Cation Transporter and their paired types. Which I've spoke on these OTC drug transporters interactions with commonly used drugs here such as metformin and berberine.

If you have access to a used-book store (Kindle and other E-books can suck it!), you can get a used copy of a fairly new edition of the PDR. If you want to truly KNOW pharmacology, that is the Pharmacology Bible for Nerds. That being said, research what big pharm defines to be a "cure" for XYZ cancer. If you really want to nerd it up, try interpreting the clinical trial methodologies and statistics.

 

[Pissbrainiac259]

What phases are we specifically asking? And are we asking which group: oxygenated heme coenzyme group or flavin adenine dinucleotide coenzyme group?

Or one could start thinking +/- learning about the process from a simple perspective via big picture which is then broken into chunks with each chunk have big pictures. For hemoglobin synthesis, you need heme and globin proteins. Heme + globin = Hemoglobin (worry about the subtypes once concept is understood). How is heme synthesized? Think smart and target your memory for the rate limiting enzymes and the upstream substrate(s) and downstream product(s) for each respective rate limiting enzymatic rxn.

For heme & hemoglobin, I remember it like this: Succinyl-CoA (refer to TCA cycle intermediate substrate) + the cofactors Glycine and B6 are converted to Aminolevulinic Acid (ALA) via the enzyme ALA Synthase. Hmmm...you think the name of this enzyme tells you anything about its function? That's a common theme in biochemistry. Another common self-explanatory enzyme is IntimidatingWord Dehydratase which means the rxn involves dehydrating 1 or more substrates which yield the formation of water (H2O) and whatever else other byproduct(s).

Fortuitously, ALA is then converted to Porphobilinogen via ALA dehydratase + H2O. We are not doing stoichiometric biochem so no need to "balance" the overall chemical equation.

Porphobilinogen then goes through several less important blah blah blah enzymatic conversions until it reaches the formation of Protoporphyrin.

Protoporphyrin + Iron is converted into Heme via Ferrochelatase (the other need-to-know important rate limiting enzyme for this net series of rxns).

And finally, Heme + Globin chains = Hemoglobin

Once you understand and commit the above biochemical pathway to memory, fill in the other details such as knowing what makes the difference between HbF, HbA, HbA2, etc.

Merely a suggestion. No more, no less.

 

[Pissbrainiac259]

What phases are we specifically asking? And are we asking which group: oxygenated heme coenzyme group or flavin adenine dinucleotide coenzyme group?

If there's chronic up-regulation of interleukin-6 this will slame the breaks on one of the main proteins involved in hepatic detoxification --cytochrome P450 as a whole. Meaning all the CYP isotypes are funked. For the cancer cure conspiracy doughheads. In the face of cancer, the cytochrome family in-which a vast majority of drugs are metabolized is now totally screwed because of this up-regulation of interleukin-6 that shuts down the metabolizing effects of these enzymes. But it's easier to say big pharma has a cure for cancer but they don't want to treat it

If ever asked by anyone or any board exam which Hepatic Cytochrome P450 subsystem is most likely responsible for the enzymatic breakdown of medication XYZ, play odds and choose the most common one (CYP3A4) if that's an option on a MCQ. If CYP3A4 is not an option, choose the 2nd most common P450 subsystem (CYP2D6) if it is an option. Anything beyond 3A4 and 2D6 is splitting statistical hairs. :lightbulb:

 

[Pissbrainiac259]

Corrected.

Nicely played. Caught it before even allowing me the opportunity. I respect that level of attention to detail. :headbang:

For future reference when discussing renal physiology/pathophysiology/pharmacology/biochemistry, simply refer to the organic anion/cation transporters as "ion transporters" and save the OTC abbreviation for the enzyme Ornithine Transcarbamylase which is involved in the Urea cycle. In simple terms, it's important in making the Nitrogen-rich urea part of urine. Is there such a thing as OTC deficiency? Yep. Rare as fuck? Yep. :headbang:

 

[Pissbrainiac259]

I would say probably not so healthy diet and possibly the tamoxifen?

Dude, I'm an idiot for not even seeing the hyperlink to the labs. Upon viewing the labs, note that the blood work done states "Comp. Metabolic Panel (14)" which means there the "Comprehensive" tests done include 14 different parameters (aka Chem-14). Would it or would it not be reasonable and more cost effective that if one were to get annual "comprehensive" blood work for proper health maintenance +/- check, the more logical choice would be either a Chem-22 or Chem-24? There is a wide regional variance in how each clinic and hospital defines "Comprehensive Metabolic Panel" and to echo a common 80's commercial, "knowing is half the battle."

With an elevated Tbili, maybe one could consider a fractionated bili which would have been included in a Chem-22 for an additional $20 and ~2 ml's of blood. That's approximately 20 lil drops but no, your retarded clinician went immediately to RUQ U/S. That's just bad medicine and not the good/cool kind of bad. :banghead:

 

[therulersback]

OP here. I'm trying to follow PB and Stewie's convo here but you guys are way over my head. I'm still itching my ass off over here so if there's something I'm missing can you spell it out in plain english for us simple folk?

update: got new bloods drawn yesterday, finally showing some improvement in bilirubin levels (3.3 now) https://imgur.com/a/B4tzbVN

 

[Pissbrainiac259]

OP here. I'm trying to follow PB and Stewie's convo here but you guys are way over my head. I'm still itching my ass off over here so if there's something I'm missing can you spell it out in plain english for us simple folk?

update: got new bloods drawn yesterday, finally showing some improvement in bilirubin levels (3.3 now) https://imgur.com/a/B4tzbVN

The systemic deposition of bile salts in the skin is the most likely source of generalized pruritus (i.e. itching) in this particular context.

 

[Pissbrainiac259]

OP here. I'm trying to follow PB and Stewie's convo here but you guys are way over my head. I'm still itching my ass off over here so if there's something I'm missing can you spell it out in plain english for us simple folk?

update: got new bloods drawn yesterday, finally showing some improvement in bilirubin levels (3.3 now) https://imgur.com/a/B4tzbVN

Just merely an observation but there seems to be a commonly reoccurring theme revolving around suggestions/recommendations pertaining to blood work +/- questions about blood work which is usually posted via pic. You should be getting accurate and succinct interpretation of blood work analyzed by your doctor. Am I missing something here b/c interpreting basic blood labs is not anywhere near close to being as difficult as interpreting a cardiac echo.

 

[Pissbrainiac259]

Hey PB! Your posts are always insightful and very informative, thank you!

If I ever choose to venture back-down the path towards being a PA again, you as well as a few other members here that I know that are physicians, I'd definitely be scratching your minds when I'm prepping for PANCE.

Nonetheless, in the opening post by the OP, he pointed out he was diagnosed with cholestasis. So I just drifted past that posts as there's not much that I can offer. Outside it was just stay hydrated and limit your junk food-high fat foods. Maybe throw in a few shots of some strong tequila! That'll clear that bile backup! ...just kidding, don't do that.

As for the Dx of the OP, D-I cholestasis, yay, nay or somewhere in between?

I've worked with some f'n awesome PA's especially in the OR.

 

[MyNameIsJeff]

OP here. I'm trying to follow PB and Stewie's convo here but you guys are way over my head. I'm still itching my ass off over here so if there's something I'm missing can you spell it out in plain english for us simple folk?

update: got new bloods drawn yesterday, finally showing some improvement in bilirubin levels (3.3 now) https://imgur.com/a/B4tzbVN

Well, given that direct (conjugated) bilirubin is elevated, it's not Gilbert's. Not Rotor's either considering your itching.

Next on the list for me would be testing for viral hepatitis. Unless you can come up with another drug you have been taking that could be causing drug induced cholestasis.

 

[therulersback]

Just merely an observation but there seems to be a commonly reoccurring theme revolving around suggestions/recommendations pertaining to blood work +/- questions about blood work which is usually posted via pic. You should be getting accurate and succinct interpretation of blood work analyzed by your doctor. Am I missing something here b/c interpreting basic blood labs is not anywhere near close to being as difficult as interpreting a cardiac echo.

Yes apparently you are missing something. I know the elevated bilirubin is the source of the itching and I know it’s cholestasis. I said as much in the OP. Based on your manner of posting I thought maybe you had some other insight into the situation. But seems it was just you and Stewie tossing each other off.

 

[Stewie]

Sorry about side-tracking your thread. I know it may seem to appear through all the gibberish of different detoxification (cytochrome CYP and other enzymatic pathways discussed) pathways may seem unrelated to your hyperbilirubinemia-cholestasis. Although, they are very much related to your particular situation in a roundabout way. We'll stop out of respect for you. My apologies.

To alluded to a previous post of mine of that possibly an--- 'unhealthy diet and tamoxifen?" May be the cause?? More often than not, I make indistinct snip comments, without questions that may help narrow in figuring out the possible cause. In particular, I should have stated more specifically 'unsanitary diet'. Some may view that as not synonymously interchangeable with 'unhealthy', in the context, of this, it is. Have you ate at like places of migrant worker food trucks, or out of the country and ate? Try to think back a few weeks prior to when the symptoms started to appear.

By no means am I suggesting that you intentionally eat in an unsanitary fashion, more so unknowingly eating at a restaurant that may have some sanitation/workers concerns that could expose the general population to hepatitis-A. This happens more often then not, unfortunately. So that's something to consider speaking with your primary about. Could be totally unrelated.

As far as the tamoxifen goes, high levels of intrahepatic estrogen can induce cholestasis by means of being an estrogen agonist in the liver. Which could muck-up thee ole bile salt export pump, therefore drug induced cholestasis. If, your estradiol was not completely controlled with an aromatase inhibitor while you was on cycle?

There's other questions that surround the aforementioned. Was you using an aromatase inhibitor with your cycle or SERM or nothing at all? Could it have been acting in an agitating manner? I dunno, as it may be a conundrum of uncertainty at this time.

Any fever with your digestive issues? As far as digestive issues go, what in particular do you mean? Abdominal pain and discomfort, diarrhea? Was your bowel movements showing undigested food?

And as Jeff had mentioned, any other drugs, OTC you've taken during this timeframe is also useful information.

 

[therulersback]

Sorry about side-tracking your thread. I know it may seem to appear through all the gibberish of different detoxification (cytochrome CYP and other enzymatic pathways discussed) pathways may seem unrelated to your hyperbilirubinemia-cholestasis. Although, they are very much related to your particular situation in a roundabout way. We'll stop out of respect for you. My apologies.

That's fine. Wasn't necessarily expecting to get anything out of this thread, just wanted to see if anyone had experience with this + anything else I should be doing.

To alluded to a previous post of mine of that possibly an--- 'unhealthy diet and tamoxifen?" May be the cause?? More often than not, I make indistinct snip comments, without questions that may help narrow in figuring out the possible cause. In particular, I should have stated more specifically 'unsanitary diet'. Some may view that as not synonymously interchangeable with 'unhealthy', in the context, of this, it is. Have you ate at like places of migrant worker food trucks, or out of the country and ate? Try to think back a few weeks prior to when the symptoms started to appear.

By no means am I suggesting that you intentionally eat in an unsanitary fashion, more so unknowingly eating at a restaurant that may have some sanitation/workers concerns that could expose the general population to hepatitis-A. This happens more often then not, unfortunately. So that's something to consider speaking with your primary about. Could be totally unrelated.

Yea no reason to suspect hep A exposure in my case, although always possibly some sort of fluke restaurant mishap.

As far as the tamoxifen goes, high levels of intrahepatic estrogen can induce cholestasis by means of being an estrogen agonist in the liver. Which could muck-up thee ole bile salt export pump, therefore drug induced cholestasis. If, your estradiol was not completely controlled with an aromatase inhibitor while you was on cycle?

There's other questions that surround the aforementioned. Was you using an aromatase inhibitor with your cycle or SERM or nothing at all? Could it have been acting in an agitating manner? I dunno, as it may be a conundrum of uncertainty at this time.

This is good point and what I was getting at by wondering if I should resume PCT. I did use adex 10mg eod ... but inconsistently. I wasn't experiencing anything I considered to be typical high E symptoms while on cycle, so I kinda half assed the adex. Now subsequently I've read some theories that high E can shut down the bile flow in the liver and that it causes cholestasis in pregnant women. Who knows.


Any fever with your digestive issues? As far as digestive issues go, what in particular do you mean? Abdominal pain and discomfort, diarrhea? Was your bowel movements showing undigested food?

I had a couple bouts of severe, violent hiccups lasting up to 14 hours at a time. I didn't even link this to digestive problems at all until the itching came through, then it all made sense together.

And as Jeff had mentioned, any other drugs, OTC you've taken during this timeframe is also useful information.

I probably combined alcohol and tylenol inadvertently a couple times by taking nyquil after drinking. ephedrine on and off. and some t3 too.

Good questions, see my answers in bold. Ultimately I fucked up by not getting bloods mid cycle since I was using a new substance. Maybe I could have detected this earlier if I had. But I didn't link the hiccups as a symptom and wasn't experiencing any other symptoms while on cycle. Ah well. Seeing the GI specialist tomorrow hopefully he will be able to confirm I am on the right track and give me something else for the itching.