So I've previously talked about how
bilirubin is involved in that cycle
of converting reactive oxygen species,
and that's a recycling that's happening in
the bilirubin and biliverdin in the process.
With this slide, I want to talk about how
it is that bilirubin is either eliminated
through the feces and urine
or how it's recycled using the
portal system of the body.
The process starts as before with heme
being converted in the biliverdin
and biliverdin being converted in
the bilirubin as we can see here.
Conjugation of the bilirubin
creates bilirubin diglucuronide
which is necessary for the
bilirubin to be soluble
in the bile system
as we can see here.
So the movement of bilirubin through the
system involves the conjugation of bilirubin
to diglucuronide to solubilize it
so that it can appear in the bile.
Moving from bile, the
enters the intestinal system where
it's metabolized by bacteria.
These bacteria convert bilirubin
diglucuronide into urobilinogen.
Now the urobilinogen has a couple of
different fates that it can undergo.
One fate is to go through the portal system
and be recycled back into biliverdin.
Recycling is important because it saves
additional things that the cell might need.
Remember that converting a biliverdin to
bilirubin and then going back was saving --
giving protection against
reactive oxygen species.
So, making more of
that cycle might help
if reactive oxygen species
are a consideration.
On the other hand, the
urobilinogen can pass
through the intestinal
system and be oxidized.
Well it's, in this case, coverted
into molecule known as stercobilin.
And stercobilin is the molecule that
gives feces the color that it has.
Instead of being recycled,
urobilinogen can also be oxidized.
Now, oxidization produces
compound called stercobilin.
And stercobilin, whose structure
as you can see on the screen here,
is a molecule that gives feces the
distinctive color that feces has.
In addition, urobilinogen can
be moved into the bloodstream.
Now, if it's moved into the bloodstream,
then it becomes metabolized
to become urobilin
and it is excreted out of the
bloodstream by filtering in the kidneys
to give the yellow
color of urine.
There are lots of possible
things that can happen here
to bilirubin as a
result of that.
One of the things that can happen if
a person has a bile duct obstruction
is that bilirubin doesn't
make it through the system
and instead bilirubin diglucuroninde
goes straight to the kidneys.
When this happens the urine
that's produced is dark
because that's the color of
the bilirubin diglucuronide
and the feces become much lighter
as a consequence of that.
Now, jaundice is a disease
that results from problems
associated with the inability
to excrete bilirubin.
It rises in the body
and gives a distinctive yellow
color to various tissues.
You can see a person in the top
photo who has a yellow skin color
arising from bilirubin
And the sclera of the eyes can
also turn yellow as seen here.
Now, one of the treatments for jaundice
is to expose a person to bright light
because light will actually
There are many possible ways
that a person can get jaundice.
One is by having a deficiency of the
enzyme that does the conjugation.
That's the one that puts the
glucuronic acid onto the bilirubin.
This disease is known
as Gilbert's syndrome.
Liver disease also causes this
because liver is a place where
this conjugation can occur.
Pancreatic cancer also
gives rise to jaundice.
And sickle cell crisis or sickle cell anemia
is of common cause of jaundice as well,
because in sickle cell anemia,
the sickle cells are being taken out of
the bloodstream with increased rapidity
and therefore causing an increased
amount of heme to accumulate.
Metabolism of heme of course is
what gives arise to the bilirubin.
Obstruction in the biliary
tract, as I've just described,
is another way in which
jaundice can be created.
And in newborns, it's not uncommon for
newborns to have problems with balance
in the amount of bilirubin
that they're making
and so they commonly develop jaundice but
it's usually very minor in newborns.
And another way to get this is through
excess hemolysis of the blood cells.
This is one of the things that's happening
for example in the sickle cell anemia,
but other diseases or
other problems can cause
blood cells to hemolyze and
give rise to jaundice.
Now, the conjugated versus the
unconjugated jaundice really refers to
what I've described as whether or
not the glucuronic acid is attached
to the bilirubin that's
associated with the jaundice.
And whether it's conjugated or
unconjugated can give some clues
as to where the problem in the body
is that's arising to cause it.
Very high levels of bilirubin
in the brain can cause damage.
So this is one of the reasons that
we have concerns about jaundice
because the brain can
be affected by that.
Conjugated bilirubin in the urine
can indicate liver disease
and so again it's telling us where
we have the problem arising.
And biliverdin that appears in the blood
is also an indication of liver disease.
Biliverdin is the distinct from bilirubin
and that biliverdin is a very dark green
color and bilirubin is distinct yellow.
Now, there are on the other hand some
benefits to bilirubin it appears,
and that's not totally
surprising if we think about it,
because bilirubin remember when it's
converted backwards to biliverdin
is protecting against
reactive oxygen species.
And reactive oxygen species
may be a factor in aging.
So, older people who have
higher levels of bilirubin,
but have no liver problems may have
more ability to function independently.
Well, in this lecture, I've talked about
the interesting compound of bilirubin
and how it affects things in our body
relating to reactive oxygen species
and how a very interesting
protein, the biliverdin reductase,
is involved in so
many body processes.