well welcome to another MedCram video we're going to talk about cholestasis
here in the liver function tests so picking up on the theme that we were
talking about before when we talked about AST ALT albumin and the protime 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 and specifically there is a gallbladder and there's also that is
connected with a cystic duct and there is a then of common bile duct and that
dumps into the intestines and the purpose of this is a two-fold is to 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-glutamyl transferase (GGT)
serum bilirubin bile acids 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 in the spleen in the reticulo-endothelial system and what it
gives up is something we call unconjugated or another way of saying
this is indirect this way its measured bilirubin and that goes to the liver and
it gets converted okay it's a big enzyme in there and it gets converted and
excreted as something different called conjugated or direct bilirubin
and there's actually ducts in here those ducts that are inside the liver just so
you are aware are intrahepatic and the ducts outside our extra hepatic 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 extra hepatic or in
the intra hepatic ducts that are supposed to get rid of the bilirubin and
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's more water-soluble is going to be able
to make it through the blood and actually get excreted out through the
kidney and so if you see bilirubinurea not emia 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 extra hepatic 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 and that's exactly what we're talking about here any kind of
blockage along the intra or extrahepatic area is cholestasis and that can
increase the alkaline phosphatase it's 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 in like 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 and 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 those 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 GGT or otherwise known as Gamma-Glutamyl Transferase
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 is
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-Glutamyl Transferase
and if it is low if the Gamma Glutamyl Transferase 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-Glutamyl Transferase
elevated okay 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 and so you can see that indirect bilirubin and the
way you would check for that is by checking a total bilirubin on the blood
test and also checking for a 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 would see that in DIC intravascular hemolysis that type
of thing or it could be the inability to convert unconjugated bilirubin to direct
conjugated bilirubin and what are one of those these diseases well the most
common disease is this thing called Gilbert's disease it looks like
Gilbert's but it's pronounced Gilbert's disease believe it or not this
condition which is autosomal dominant 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 glucuronosyltransferase 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 in ability to excrete the direct conjugated
bilirubin after it's been processed back into the biliary ducts this is the
intrahepatic ducts or in the extra hepatic 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
like we said 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
a total bilirubin and a direct bilirubin you'll see that the direct bilirubin is
more than 50 percent of the total bilirubin that lends you to believe that
there is some either intrahepatic or extra hepatic 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 hyperbilirubinemia gaited 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