HiddenTruth said:
Few questions guys:
This may all tie in towards the end, and if it does, please explain, thanks.
1. Why is it that u don't get jaundice with intravascular hemolysis. HgB gets bound to haptoglobin and taken up by MP, and gets processed, and doesn't the BR get spit back out, like it would in extravasc hemolysis (taken up by MP in spleen)? Or, what's the fate of that HgB then?
2. This is tied to the aforementioned q. What happens to indirect and direct BR in the case with intravasc hemolysis? (can someone explain the path it takes) What about urine BR and urine urobillinogen?
3. During extravasc hemolysis, you have an increase in UCB in the blood bound to albumin. So, does this mean that direct will also be elevated, because the UCB can't be spilled into urine (lipid soluble; acholuria), and it ges taken up to get conjugated? So, would all these parameters be elev: UCB, CB, urine urobillinogen?
Thanks a lot.
Ya bilirubin **** is confusing i hear ya. I will try to give you an answer for all 3 in one explanation instead of answering each one individually but let me know if i didnt cover something you needed as i am not the most clear explaner of things but ill give it a shot.
So lets start out with intravascular hemolysis--> lysis of RBC in serum leads in release of hemoglobin--> the hemoglobin binds to haptoglobin and makes a complex--> this hem-hap complex is taken up by Mphages where hemoglobin is broken down and the heme group gets converted to bilirubin and released back into teh blood as Unconjugated BR--> the unconj BR binds to albumin.
Now following lysis of rbcs, depending on how much lysis occurs, there is only so much haptoglobin, therefore once its gone the excess hemoglobin cannot bind to hapto, therefore no hem-hap complexes can be made and therefore Mphages cannot take up just plain hemoglobin unless it is in the form of a hem-hap complex which it can recognize. Therefore this hemoglobin free in the serum, and unbounded to haptoglobin is excreted in the urine.
Therefore we can point out a few things
1. lets say just for sake of clarity that 75% of all the hemoglobin released in the lysis was able to bind to haptoglobin and 25% was not due to lack of haptoglobin, therefore 75 percent of the hemoglobin was in essence broken down in Mphages and Unconj. Bilirubin was ultimatly produced and is now in the serum bound. 25% of hemoglobin however was lost in the urine and therefore none of it was ever broken down, and thus none of that 25 percent got converted to bilirubin.
2. The above explains the classic signs of intravasc Hemolysis- Hemoglobinuria, Hemoglobinemia, Jaundice(will explain in a min)
Now lets talk extravascular-lets say for whatever diseased the damaged RBC goes through Spleen and is taken up by the splenic Mphages and hemoglobin from cell is broken down to hemoglobin and released as unconj. Bilirubin, which binds to albumin. Now here is a big DIFF- notice in extravascular,100% of the hemoglobin from the damaged RBC was taken up by the Mphages and thus 100 percent of the hemoglobin of the RBCs was converted to bilirubin.
So the classic findings of extravasc hemolysis is Jaundice with NO hemoglobinuria or hemoglobinemia(because all hemoglobin was taken up by splenic Mphages.
So at this point,regardless of which path, intra or extra you have unconjugated bilirubin bount to albumin in the plasma. From there, none can go into kidney or urine, so all of it ends up at the liver, where it is removed from albumin, taken up by hepatocyte, conjugated, secreted intil bile--> within the gut, the conjugated bilirubin within the bile, is mostly deconjugated by bacteria and converted to urobilinogen.-->70% of uro is excreted in feces, 20% is put into enterohepatic circulation back to liver for reconjugation and excretion, and 10% is absorbed into system circulation, where the urobil is excreted in the urine. So you can see in this relationship and in general, the more Bilirubin the liver takes up-the more it conjugates and excretes into bil-->the more of it gets turned into urobilinogen-> the more urobil there is, the more goes out each path- which means the 10 percent that is absorbed systemically is increased with more total bilirubin excretion.
Now back to all the unconjugated bilirubin we have from our intra and extravasc hemolysis-so lets say we have 2 pools
1. Extravascular pool- Since 100% of the hemoglobin was converted to unconj bilir lets say we have 100 Unconj. Bilirubin bound to albumin
2. Intravascular pool produced only 75% of its hemoglobin to bilirubin so lets say we have 75 bilirubin bound to albumin.
Now for example sake, lets say the maximum a healthy liver can take in, conjugate and excrete is 100- therefore the liver will take up 100 unconj bilirubins and excrete it therefore neither path will be a problem and you will have no jaundice from either since all the bilirubin was successfully excreted.
But to illustrate how jaundice occurs, lets say the liver had a capacity of 75, therefore the amount in the intravasc path would be fine and no jaundice would occur from the intravasc path but the extra path has 25 bilirubins too many for the liver to handle, therefore those 25 unconjugated bilirubins are stuck in the serum of the body, circulating around to various tissues--> lets say the icterus of the eye. The bilirubin in tissues now causes jaundice since it has no way to be excreted.
Now lets say the liver capacity in someone with liver disease is 50- in this case both paths would be too much to handle and intra and extra would produce jaundice. Basically if a healthy liver is functioning properly, neither intra or extra will cause jaunidice in a mild/moderate hemolytic episode, however if one were MORE LIKELY to cause jaundice, it would the extrav. path for reasons illustrated above. So basically it is a balance of liver function and bilirubin produced and the answer to your first question is both types CAN cause jaunice, but normally niether do, but if one were to happen its going to be extrav, that is why texts/review books tend to list jaunidice under extravasc.
Now as far as urine is concerned
Intravascu- Hemoglobinuria and Urobilinogen will be in teh urine. The urobilinogen is directly related to amt of bilirubin produced and processed by liver. If intravas episode released 50 bilirubins that are fully processed by liver it might give 2 into urine. If intra released 100 bilirubins and liver was healthy and able to process all 100 then maybe 4 would be released as urobil into urine.
Extravasc. No hemoglobinuria is present as discussed way up top, and justlike intra, there is Urobilinogen in urine, based on amount of bilirubin produced in teh episode, justl ike explained for intrav.
Now both of those are assuming a liver is healthy and processed the bilirubin. If you get into diseased where the liver conjugates bilirubin but cant excrete it, then you can have a back up of conjugated bilirubin into system blood and urine excretion of conjugated bilirubin out urine but the ONLY way conjugated gets into urine is if the liver takes up unconj bilirubin, conjugates it and then has a problme excreting it- it will "back up" into systemic circ.> But under your 2 examples the only things youl see in urine is urobil( in both tyeps) and hemoglobin( in intra). gee that was long sorry about that, i geuss it isnt the most concise explanation, hope it was good for something!
