Today we'll talk about the general
approach to the patient with jaundice.
So we'll start with a case.
An 85-year-old woman is admitted to the
hospital with fever, epigastric pain and jaundice.
She has no known history
of liver or biliary disease.
Her vitals are notable for temperature
of 39.3C and heart rate of 110 bpm.
Physical exam reveals jaundice and right upper
quadrant tenderness without rebound or guarding.
No hepatosplenomegaly is noted.
Her labs reveal a white cell count of
20,000/uL, ALT 420 (U/L) AST 360 (U/L)
and total bilirubin 8.5 (mg/dL)
with a direct bilirubin of 6.8 (mg/dL).
Right upper quadrant ultrasound reveals dilated
intra and extrahepatic bile ducts with gallstones
but no findings of cholecystitis.
So what is the most likely diagnosis?
To help us answer that question,
let's look at some key features.
So she has fever,
epigastric pain and jaundice.
This should prompt you to
remember Charcot's triad of cholangitis.
In addition, on her physical exam and her
labs , we note that she meet sepsis criteria
with fever, tachycardia
and a high white count.
likely from a biliary source
given her elevation in her liver test.
She has hyperbilirubinemia with a
pattern of hepatocellular injury as well.
And on her ultrasound, we see common bile duct
obstruction from the dilation of the bile ducts
likely from a gallstone
but we're not sure yet.
So now let's talk about
the concept of jaundice.
Jaundice is a clinical sign when
there is a disorder in bilirubin circulation
typically only seen once serum
bilirubin is above 2.5-3 (mg/dL).
There are three potential causes including:
abnormal bilirubin metabolism, hepatocellular
dysfunction and biliary obstruction.
So, there's a lot of terminology involved
with discussing hyperbilirubinemia.
We'll have to first recall that bilirubin is
conjugated in the liver for then excretion.
So labs may report a total bilirubin and
they may also report a fractionated bilirubin
as either direct or indirect bilirubin.
What do these terms mean?
So, a direct bilirubin
refers to conjugated bilirubin.
So that is bilirubin that has
already been conjugated by the liver.
Whereas indirect bilirubin
refers to unconjugated bilirubin
so before it has reached
the liver for conjugation.
It is helpful to think about
jaundice in several large categories
so we can think about it first in causes that
occur before we get to the liver so prehepatic.
We may talk about causes
within the liver, so intrahepatic.
And lastly posthepatic or after the liver.
So prehepatic causes tend to be from
hemolysis or the breakdown of red blood cells.
Intrahepatic causes maybe from viral hepatitis,
cirrhosis, or tumors or malignancies within the liver.
And posthepatic causes tend to be
from gallstones or different types of cancer.
So in your initial approach to
working up a patient with jaundice,
these are some lab studies that
you should make sure to get.
The first is your liver panel.
So this includes your AST, ALT,
total and fractionated bilirubin,
total protein and albumin.
Note that you may also want to get a
GGT or gamma glutamylytanspeptidase.
This is a more specific test than alkaline phosphatase
because it is more specific to the hepatobiliary system
whereas alkaline phosphatase can be
elevated from other conditions involving the bone.
You should also get a
complete blood count or a CBC.
This is specifically to look for evidence of
hemolysis by which you may see anemia.
You should also check your coagulation studies, again
this is to look for potential signs of hemolysis.
And lastly, an abdominal ultrasound is
helpful to look for any signs of obstruction.
So, there are many different ways to think about
the diagnostic approach to hyperbilirubinemia.
This is one way that I think about it.
So when you're faced with high
bilirubin, you can break it down into either
an isolated elevation of the bilirubin or an elevation
of a bilirubin along with an abnormal liver test.
When you have an
isolated bilirubin elevation,
you can break it down into whether
it's unconjugated or mostly conjugated.
If it is mostly unconjugated, this is
indirect bilirubin, your causes include
hemolysis and other syndromes like
Gilbert Syndrome and Crigler-Najjar.
If it is mostly conjugated which
remember, is direct bilirubin
then your causes are simply things like
Dubin-Johnson or Rotor Syndrome.
On the other hand, if you also
have abnormal liver chemistry test,
then we can break it down into either a
hepatocelllular pattern or a cholestatic pattern.
In the hepatocellular pattern, your causes
are quite extensive but include viral hepatitis,
drug-induced liver injury, autoimmune
hepatitis and inherited conditions like
Wilson's and alpha-1
antitrypsin and hemochromatosis.
On the other hand, and within the cholestatic
pattern of elevation, you will have things like:
gallstones, medications, PSC and PBC, cholangitis
and various cancers or infiltrative diseases.
So now, let's go back
to our prehepatic causes
The mechanism by which people develop prehepatic jaundice
is from metabolism of heme in the red blood cells.
So as red blood cells get
destroyed by hemolysis,
they then have breakdown of hemoglobin
which then leads to production of bilirubin.
Remember again, this is
unconjugated, indirect bilirubinemia
because this is prior to transport to liver where
the bilirubin will be conjugated and excreted.
So, there are many
different types of hemolysis.
We can break them down
in several large categories.
First you may have a defect in
your red blood cell membrane
as in G6PD deficiency or spherocytosis.
You may have a problem with the hemoglobin structure
itself as in sickle cell disease or thalassemias.
And then there are other miscellaneous
causes such as autoimmune hemolytic anemia
or a large category of
microangiopathic hemolytic anemias.
You may have resorption of a large hematoma
or various medications
can also induce hemolysisp
Now let's move to our intrahepatic causes.
So these are... there are very many
intrahepatic causes of cholestasis
including viral hepatitis, infiltrative diseases,
various cancers, medications, and genetic causes.
Know also that you may have cholestasis from
sepsis itself or in states of pregnancy.
Now let's move to our posthepatic causes.
So, after the liver, causes of cholestasis
include obstruction from gallstones,
various infections or
strictures of the biliary system.
You may have pancreatitis
that leads to an obstruction
and many different cancers can all impact to these
area leading to an obstruction and thus, jaundice.
So now let's return to our case.
An 85-year-old woman is admitted
for fever, epigastric pain and jaundice
which is Charcot's triad of cholangitis.
She also meets sepsis criteria
and her hyperbilirubinemia is mostly,
now we know, a conjugated
In addition, her ultrasound shows common bile duct
obstruction and she has evidence of gallstones.
So putting this all together, we now know
that she most likely has ascending cholangitis
based on the Charcot's triad and recall that
when you have a gallstone leading to obstruction,
this is a posthepatic cause of jaundice.
So her most likely diagnosis is ascending cholangitis
from a gallstone obstructing the common bile duct.