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