Welcome to another MedCram video we're gonna talk about cholestasis here
and liver function tests so picking up on the theme that we were talking about
before when we talked about ast alt albumin and the pro time we were talking
about the actual liberal per n comma 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 the mat 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 help with digestion of fats but also to get rid of
some products specifically Hema 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 will transfer a 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 and the spleen and 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 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're aware are
ah hepatic and the Ducks 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 extra paddock or
in the intra hepatic ducts that are supposed to get rid of the bilirubin and
the bile acids what's gonna happen is the conjugated bilirubin is going to
build up in the blood and the unconjugated bilirubin is gonna build up
in the blood and you're gonna 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 Billy Ruben urea not emia but urea that is the presence of
conjugated bilirubin in the blood you will not see unconjugated bilirubin
being passed through the kidneys so if you see Billy Ruben 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 we also got out Foss 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 all
along the intra or extra hepatic 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 we have an elevated alkaline phosphatase you're not
exactly sure what's causing it is a 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 duct tell 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
egg GGT or otherwise known as gamma glue Tamil trance race now this is pretty
good because you do see an increase in GG T 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 glue Tamil transferase and if it is low if
the gam of the Tamil transfer ace 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 glue Tamil
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 gonna 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 di see 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 G Bears disease
it looks like Gilbert's 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 gluten will transfer ace 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 gonna 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 gonna pass from the blood into the kidney and you're gonna pick up
hyperbilirubinemia
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
you