Hepatic versus post-hepatic jaundice; conjugated vs. unconjugated hyperbilirubinemia

[E.S.Prakash]

Dear Year 1 Student,

I do not have the slides you are referring to so I cannot answer in
reference to that but I wish to explain that hepatic and post-hepatic
jaundice are distinct. You will obviously get to details of bilirubin
metabolism shortly in the biochemistry module and later in the GIT
course but here is some information if you like:

One way jaundice (which is due to hyperbilirubinemia) is classified is
as: pre-hepatic, hepatic and post-hepatic.

There is another way and that is to simply classify hyperbilirubinemia
as predominantly unconjugated or predominantly conjugated
hyperbilirubinemia but the former is more often used in day-to-day
clinical practice.

Bilirubin (i.e., unconjugated bilirubin) is conjugated by liver
cells.

Urobilinogen is formed by the action of intestinal bacteria on
bilirubin diglucuronide that reaches the intestinal lumen. Once formed
there, a fraction of it is absorbed by the intestinal epithelial cells
and thence into the blood stream (and eventually into urine)

The term "pre-hepatic" refers to the fact that hyperbilirubinemia is
because of an increased load of unconjugated bilirubin for the liver
cells to conjugate; so these individuals have an increased serum level
of total bilirubin, unconjugated bilirubin as well as conjugated
bilirubin (but if you look at ratios the unconjugated form of
bilirubin predominates over the conjugated form). If we take care not
to be misled by ratios, we can understand why these individuals
excrete an excess of urobilinogen in urine. It is simply because they
conjugate more bilirubin and excrete more conjugated bilirubin in
bile.

Hepatic jaundice is jaundice that is associated with hepatocellular
hypofunction; what comes of as "paradoxical" (it did to me when I
learnt this as it has now happened to you when you say "when liver
cells are diseased, urobilinogen level should decrease") is the fact
that the the hyperbilirubinemia is "conjugated". By "conjugated
hyperbilirubinemia", I mean that the increase in "total bilirubin"
level in 'hepatic jaundice' is largely due to an increase in
"conjugated bilirubin".

We would think that when liver cells are damaged, the ability of liver
cells to conjugate bilirubin (and consequently form urobilinogen)
would be depressed and expect unconjugated bilirubin to predominate.
It so happens that the ability of liver cells to conjugate bilirubin
is preserved despite hepatocellular dysfunction and when such
individuals are jaundiced they typically have a predominance of
conjugated bilirubin over unconjugated bilirubin. Such individuals
will have other evidence of "liver cell injury" or "hypofunction" in
the form of elevated serum levels of alanine and aspartate
transaminases, increased prothrombin time etc. That is why we use the
term "hepatic" jaundice.

Post-hepatic jaundice refers to hyperbilirubinemia that is secondary
to obstruction to flow of bile into the duodenum (as an example, such
obstruction could be due to stones in the extrahepatic biliary
system). If the obstruction to flow of bile is total and complete,
then urobilinogen cannot form (see above) and thus such individuals
wouldn't excrete (or excrete less) urobilinogen in the urine or stools
(thus their stools would be pale). These individuals have conjugated
hyperbilirubinemia because the conjugation processes in the liver are
unaffected.

Having said this, I can now add that inherited defects in bilirubin
conjugation in liver (example, inherited deficiency of UDP-glucuronyl
transferase) is a "hepatic" cause of jaundice but such individuals
will obviously have unconjugated hyperbilirubinemia. Thus, not all
individuals with a "hepatic" cause for jaundice indeed have conjugated
hyperbilirubinemia. This is the reason why classification of
hyperbilirubinemia simply as "predominantly conjugated" and
"predominantly unconjugated" is better.

However, if we keep the inherited forms of hyperbilirubinemia due to
hepatic defects aside, then the classification of jaundice as
prehepatic, due to hepatic disease (hepatic jaundice), and due to
disease downstream of hepatic parenchymal cells (post-hepatic) does
direct us to the most likely underlying cause of jaundice, and this is
why this classification has persisted.

Best

Prakash
*****************


On Thu, Oct 14, 2010 at 3:23 PM, MBBS Batch 16
<mbbs.b...@gmail.com> wrote:

From a Year 1 Student:

Sir, I have a doubt about hepatic jaundice. According to the slides
provided (the last slide), it shows that the urobilinogen
concentration will decrease in the plasma. However, wikipedia stated
that urobilinogen concentration will increase. So, what is the actual
cause for hepatic jaundice? If the cause is hepatocytes damage, then
the urobilinogen level will decrease. If duct obstruction is the
cause, then the level will increase.

If the cause is duct obstruction, then it would be the same as post-
hepatic jaundice. So is hepatic jaundice and post-hepatic jaundice the
same?

Thank you for your time.