Hidden away under the ribs. It is a
non-complaining organ. The bowel complains
a lot. The liver doesn't. My patients
who come in with their chronic
Hepatitis C, and they say, Oh my liver is
giving me all this horrible pain right
here. Okay, a little lesson here, the
liver is over here. (laugh) The liver
doesn't cause much pain.
Okay, so what we're gonna try to do is say
What tools do we have for trying to
identify disease in the liver?
There are nonspecific things. If you
look at that list, lots of diseases cause
these things. So, they're really
nonspecific. They tell you there's nothing
really wrong, but they don't necessarily
tell you what the disease is. Something
that's a little more specific is if
patients are jaundiced. If they have
yellow sclerae. If their urine looks like
coca-cola color, although acute tubular
necrosis that you probably learned of in
kidney can do that also, or hematuria can.
Patients with chronic liver disease can
develop ascites, swelling in the abdomen,
Rich Mose will tell you about that. They
can develop peripheral edema, but you
already know that peripheral edema can
be caused by many things. What would be
another common cause of peripheral edema?
- Heart failure. -Heart failure. And
renal failure requiring dialysis can do
it. So, some of these are also not very
specific. And they really mean the liver
is very, very badly damaged. You are at
an end stage. It doesn't help you with
early stage. We're gonna talk about
several categories of tests that you can
use to screen for liver disease. And
that's what most of this talk will be
about. How can we identify ongoing liver
cell injury, problems with bile flow,
which is called cholestasis. Then we'll
talk a little bit about do we have any
ways of calculating liver function or
quantitative? Then you actually use
pattern of liver tests abnormalities to
start sorting liver diseases into groups.
This is a lot easier than diarrhea,
I promise. Finally, there is diagnosis
of specific liver diseases. The other
lectures you're gonna hear in the next
couple of days, we'll talk mostly about
those. So, how can you tell the liver
cells died or were injured?
Transaminases, which many people call
liver function tests, even though they're
not, or liver enzymes, are two enzymes:
alanine aminotransferase,
aspartate aminotransferase. Now, what
are these? Well they have a normal
function in the liver. They're used for
transferring amino group from one amino
acid to another and to make amino acids.
That has nothing to do with their role as
liver injury tests. They just happen to be
there in very large amounts. They're
easily measured. An ALT is very specific
for liver. AST is also in muscle.
Just to make life confusing. Again, ALT is
liver only. It's in the cytosol. AST is
in other tissues, although the liver has
a huge amount. In the cytosol, there's a
mitochondrial fraction. Now depending
on the method your laboratory uses, it
is a normal range. The old normal ranges
use to go up to 70. Now, in most labs,
they're down to about 30 or 35 because
the methods were changed a little bit.
And we realize that some of our normal
population wasn't all that normal.
There's always some in your blood because
liver cells turn over! They don't survive
forever. They're long-lived, but they die.
So there's always some. Another fact that
we will talk about later is that they
require a B vitamin pyridoxal 5 phosphate
as an essential cofactor. And that works
into a few little interesting clues you
can use to look at alcoholic liver
disease. So these are usually measured
in our automated systems in the lab. You
throw the serum with the substrate into
a little tube, and it runs through,
and a colored product is developed,
and you can measure that with a photo
detector, and then you could change the
absorbance or light to enzyme activity.
So what the lab measures is the enzymatic
activity of these, not the protein.
And there's no DNA here, so molecular
biology's out. So this is my crude
drawing of a liver cell that gets injured,
and here's the bile canaliculi. You got
mitochondria. You got a nucleus. You've
got AST in several places. You got ALT
in the cytosol. When the liver cell
finally ruptures, these things can get
directly into blood because you've got
that nice fenestrated endothelial. So
they're easily detectable in blood. There
convenient, there's a lot of it in liver.
It directly gets released into blood.
So, you can really- this is a very
sensitive and relatively specific measure
of ongoing cell injury. So, I kind of
joke that it's telling you how many
liver cells died in the last 24 hours.
Because these enzymes have been cleared
by the reticuloendothelial system or
other things. They don't tell you how
many liver cells died two weeks ago.
They don't tell you how many are going to
die tomorrow. They told you what injury
is going on right now.
And so you can look at patterns in
different diseases. Diseases that kill
a lot of hepatocytes in a fairly short
period of time are going to have much
higher levels of this in blood at any
given time. Then people who have a disease
where there's only a little bit of damage
occurring. Doesn't tell you about duration
of disease. It tells you how much injury.
So, if I give you a severe attack of
acute viral hepatitis, and you're really
sick, and a lot of liver cells are dying
everyday, you're going to have values
in the thousands. It could even be 5,000.
If you have a much milder disease
clinically, that usually means a lot less
cells are being killed at any one time,
going to have a lower level. Hepatitis C,
which you'll hear about tomorrow and
next week, is a virus that causes a
low-grade chronic injury. So on a
day-to-day basis, you have a very low
level of these enzymes. [06:51]