Welcome to another MedCram video. We’re going to talk about cholestasis here in liver function tests. So picking up on the theme that we were talking about before when we talked about AST, ALT, albumin, and PRO (prothrombin) time, we were talking about the actual liver parenchyma itself.
Next, we want to talk about cholestatic. What does that mean? Well, we talked about the liver， specifically, there is a gallbladder, and that is connected with a cystic duct. There is a then of common bile duct, and that dumps into the intestines. The purpose of this is two-fold: help with digestion of fats, but also to get rid of some products, specifically heme products, and that’s what we’re going to talk about next. We’re going to talk about things like the alkaline phosphatase, the gamma gluten transferase, serum bilirubin, bile acid, and things of that nature.
So let’s go through that very carefully. Okay, so let’s draw a picture here of what’s going on schematically. Here is our liver. This is schematic, and we’ve got the red blood cell. So we’ve got blood over here, which lasts for about a hundred and twenty days. So here’s our red blood cell, and it gets broken down after a while, and spleen and the reticuloendothelial system, and what it gives up is something we call unconjugated, or another way of saying this is indirect (the way to measure it) bilirubin.
And that goes to the liver, and it gets converted. So there is enzyme in there, and it gets converted and excreted as something different called conjugated, or direct bilirubin. And there are actually ducts in here. Those ducts that are inside the liver, just so you are aware, are intrahepatic, and the ducts outside are extrahepatic.
Now the kidney also fits into this, in that the conjugated bilirubin, and not the unconjugated bilirubin, can be excreted through the kidney. So what do I mean by that? If for some reason there is a blockage here in the extrahepatic or in the intrahepatic ducts that are supposed to get rid of the bilirubin in the bile acids, what’s going to happen is the conjugated bilirubin is going to build up in the blood, and the unconjugated bilirubin is going to build up in the blood, and you’re going to be able to check it with a blood test.
However, only one of these things, and that is specifically the conjugated bilirubin, because it’s conjugated, it is more water-soluble, is going to be able to make it through the blood and actually get excreted out through the kidney.
So if you see bilirubin urea, not amenia, but urea, that is the presence of conjugated bilirubin in the blood. You will not see unconjugated bilirubin being passed through the kidney. So if you see bilirubin in the urine, that means you must have conjugated bilirubin in the blood, and that means either intrahepatic or extrahepatic obstruction.
Okay, so with that, let’s start going through this methodically. The first test that I want to talk about is the presence of alkaline phosphatase (ALK Phos). You’ll see this on a regular, complete metabolic panel. It has a low specificity for cholestasis because there are three things that can increase the level of alkaline phosphatase.
The first thing is cholestasis, which is exactly what we’re talking about here: any kind of blockage along the intra-hepatic or extra-hepatic area is cholestasis, which can increase the alkaline phosphatase. Alkaline phosphatase is what we call an inducible enzyme, which means it takes a little while for it to happen. It’s not going to happen right away, but it will happen. The second thing that can cause an increase in alkaline phosphatase is pregnancy.
The third thing that can cause an increase in alkaline phosphatase is bone disease, specifically bone growth. So where would we see something like that? For instance, Paget’s disease, where you have increased bone turnover, also in blastic, not lytic, type of cancers. What are the blastic type of cancers? Prostate and breast can cause blastic lesions. So cholestasis is just one of those things. So if you have an elevated alkaline phosphatase, you’re not exactly sure what’s causing it. Is it cholestasis pregnancy or bone growth?
But cholestasis is one of those things. If we see a blockage here, you will get an increase in alkaline phosphatase, but it’s got a low specificity for cholestasis. The biliary ductal cells is what increases it. You can see an increase in most types of liver damage as a result of that, and high levels are seen in cholestasis.
So because of that uncertainty, there’s another test called a GGT, or otherwise known as Gamma-glutamyltransferase. Now, this is pretty good because you do see an increase in GGT in cholestasis, but you don’t see it in bone disease.
So, I’ll put a big X there. You do not see it in bone disease, just cholestasis. So the way this is used as if you have a patient with a high alkaline phosphatase, and you want to see whether or not this is GI-related or liver-related, you can get a Gamma-glutamyltransferase, and if it is low, if the Gamma-glutamyltransferase is low, that means it’s not from the liver. If it’s high, then that means it probably is from the liver. Interestingly, alcohol (ETOH), can also make Gamma-glutamyltransferase elevated.
So let’s take a look at our chart again. You can see here that if we have a lot of breakdown of blood products, we’re going to get a lot of unconjugated bilirubin, so you can see that indirect bilirubin. The way you would check for that is by checking total bilirubin on the blood test and also checking for direct bilirubin, and the difference between these two is going to be your indirect bilirubin.
If you see that that is high, it can either mean that you have a lot of breakdown of blood products. So where would we see that? We’d see that in DIC (Disseminated intravascular coagulation) intravascular hemolysis, that type of thing, or it could be the inability to convert unconjugated bilirubin to direct conjugated bilirubin. What are one of these diseases? Well, the most common disease is this thing called Gilbert’s disease, it looks like Gilbert.
But it’s pronounced G-Bears disease. Believe it or not, this condition is present in up to 5% of the general population, and you would see an increase in the total bilirubin up to about 3.0 milligrams per deciliter. And this is a result of decreased expression of this enzyme glucuronyltransferase, which is the important step in the conversion of indirect bilirubin to direct bilirubin.
Now, if you get a problem anywhere along here, so liver damage, drug damage, inability to excrete the direct conjugated bilirubin after it’s been processed back into the biliary ducts. This is the intrahepatic ducts or in the extrahepatic portion. Let’s say you’ve got a tumor of the pancreas, or you’ve got a stone blocking the common bile duct, you will get an increase in this conjugated direct bilirubin, and it will back up into the blood.
Not only that, you’ll also see an increase in unconjugated or indirect bilirubin. So how do you tell if that’s what’s going on? Well in this situation, because the blockage is here, you’re going to see at least 50% of the bilirubin in the blood being of the direct type. So if you check total bilirubin and direct bilirubin, you’ll see that the direct bilirubin is more than 50 percent of the total bilirubin. That led you to believe that there is some either intrahepatic or extrahepatic obstruction causing this cholestatic jaundice.
Now because direct bilirubin is building up in the blood, and because it is more water-soluble, it’s going to pass from the blood into the kidney, and you’re going to pick up hyper bilirubin urea, and that’s another sign that you’ve got direct conjugated bilirubin in the blood.
Okay. So with this background in the next lecture, what we’re going to talk about is the type of patterns that you would see in actual diseases. We’re going to talk about acute hepatitis, chronic hepatitis, and cholestatic liver disease. So join us for the next lecture. Thanks very much!