Liver Function Tests - an overview
Summary
TLDRThis educational video by Dr. Matt delves into liver function tests, explaining what they are and their purpose. It covers key enzymes like AST, ALT, ALP, and GGT, and liver-produced substances like albumin, prothrombin time, and bilirubin. The video discusses why these tests might be ordered, such as for patients with liver disease, medication-induced liver injury, or high-risk groups. It also provides a schematic approach to interpreting test results, distinguishing between jaundice causes, cholestasis, and hepatocellular injury, offering valuable insights for medical professionals.
Takeaways
- 𧬠Liver function tests (LFTs) are blood biomarkers that indicate liver health, including enzymes and liver-produced products like albumin and bilirubin.
- π¬ Enzymes such as AST (Aspartate Transaminase), ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), and GGT (Gamma Glutamyl Transferase) are released by the liver and can signal liver injury if elevated.
- π Albumin, prothrombin time, and bilirubin levels are liver-produced substances that, when abnormal, suggest liver dysfunction in protein synthesis, clotting factor production, and bilirubin processing, respectively.
- π₯ LFTs may be ordered to investigate liver disease, medication or poison-induced liver injury, alcohol use, family history of liver issues, or high-risk groups such as those exposed to viral hepatitis or illicit drugs.
- π Jaundice, a yellow discoloration of skin and eyes due to bilirubin buildup, can be assessed through LFTs to determine its cause, such as pre-hepatic, intra-hepatic, or post-hepatic conditions.
- π Bilirubin levels above 1.2 mg/dL may indicate jaundice and require further investigation into the cause, which could be related to red blood cell breakdown or liver processing issues.
- π« High levels of ALP and GGT in conjunction suggest cholestasis, a blockage in bile flow, but must be differentiated from non-liver sources like bone tissue.
- βοΈ AST and ALT are key indicators of hepatocellular injury; their levels and ratio can help differentiate between acute and chronic liver conditions, with AST being more sensitive to alcohol.
- π Decreased albumin and clotting factors, along with increased clotting time, indicate liver's compromised ability to produce necessary proteins and regulate blood clotting.
- π Hepatocellular injury affects bilirubin processing, leading to issues in secretion and excretion, and can result in both pre-hepatic and post-hepatic jaundice.
- π§ Understanding the nuances of LFTs, such as the role of individual enzymes and liver-produced substances, is crucial for diagnosing and managing liver conditions.
Q & A
What are liver function tests, and what do they measure?
-Liver function tests, also known as liver chemistries, are blood biomarkers that indicate how well the liver is functioning. They measure the levels of certain enzymes and proteins that are either produced by the liver or are indicative of liver function, such as AST, ALT, ALP, GGT, albumin, prothrombin time, and bilirubin.
What is the significance of enzymes like AST and ALT in liver function tests?
-AST (Aspartate Transaminase) and ALT (Alanine Transaminase) are enzymes that are released from the liver. Elevated levels of these enzymes can indicate liver injury or disease, as they are markers of hepatocellular damage.
What are the liver-produced products that liver function tests measure?
-The liver-produced products measured by liver function tests include albumin, a protein that helps maintain blood volume and pressure; prothrombin time, which reflects the liver's ability to produce clotting factors; and bilirubin, which is processed and conjugated by the liver for excretion.
Why might a healthcare provider order liver function tests?
-Liver function tests may be ordered to investigate potential liver issues, such as a history of liver disease, exposure to hepatotoxic medications, alcohol use, or a family history of liver disorders. They can also be used as a screening tool for high-risk patients or to monitor liver function in patients with conditions that may affect the liver.
What is jaundice, and how can liver function tests help diagnose its cause?
-Jaundice is a yellow discoloration of the skin and eyes due to a buildup of bilirubin. Liver function tests can help determine the cause of jaundice by measuring the levels of bilirubin and other liver enzymes, which can indicate whether the issue is pre-hepatic, hepatic, or post-hepatic.
How does the liver process bilirubin, and why is it important?
-The liver processes bilirubin by conjugating it, making it water-soluble and allowing it to be excreted via bile. This process is crucial for the elimination of bilirubin from the body and helps maintain normal bilirubin levels, which is important for overall health.
What is the difference between pre-hepatic, intra-hepatic, and post-hepatic causes of jaundice?
-Pre-hepatic causes of jaundice are related to increased red blood cell destruction or issues with the enzyme that conjugates bilirubin. Intra-hepatic causes involve problems within the liver cells, such as diseases affecting liver function. Post-hepatic causes are related to obstructions in bile flow, such as blockages in the bile ducts.
How can the ratio of direct to total bilirubin help determine the cause of jaundice?
-A higher proportion of direct bilirubin compared to total bilirubin can suggest a post-hepatic cause of jaundice, such as cholestasis, where there is a problem with bile excretion. Conversely, a higher total bilirubin compared to direct bilirubin may indicate a pre-hepatic cause, such as increased red blood cell destruction or issues with bilirubin conjugation.
What role do bile acids play in the diagnosis of cholestasis through liver function tests?
-In cholestasis, bile acids can accumulate and cause an increase in the activity of enzymes such as alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), which are found on the bile canalicular membrane of hepatocytes. Elevated levels of these enzymes can indicate a problem with bile excretion.
How can the levels of AST and ALT help differentiate between acute and chronic liver injury?
-Significantly elevated levels of AST and ALT, such as 10 times the normal value, can indicate acute liver injury, which could be due to factors like viral hepatitis, drug toxicity, or hypoxic injury. Moderate increases in these enzymes, around five times the normal value, may suggest chronic liver injury, possibly due to conditions like fatty liver disease or chronic viral hepatitis.
Why might the ratio of AST to ALT be higher in cases of alcohol-induced liver injury?
-The higher ratio of AST to ALT in cases of alcohol-induced liver injury is due to the fact that AST is more sensitive to alcohol's effects on the mitochondria, which can cause it to leak into the bloodstream at a higher rate than ALT. Additionally, chronic liver conditions like cirrhosis can also lead to a higher AST to ALT ratio.
Outlines
π§ͺ Introduction to Liver Function Tests
Dr. Matt introduces the video on liver function tests, explaining that these blood biomarkers indicate liver health. He outlines the video's agenda: defining liver function tests, discussing reasons for their use, and analyzing a schematic to understand abnormalities. Key liver enzymes like AST, ALT, ALP, and GGT are mentioned, as well as liver-produced substances such as albumin, prothrombin time, and bilirubin. The importance of these indicators in assessing liver function and disease is emphasized.
π‘ Causes and Diagnosis of Jaundice
This paragraph delves into jaundice, a condition characterized by yellowing of the skin due to bilirubin buildup. It explains the origin of bilirubin from red blood cell breakdown and its journey through the liver for processing. The liver's histological unit, the lobule, its blood supply, and bile excretion process are described. The role of hepatocytes in bilirubin conjugation and the significance of direct bilirubin (DB) in diagnosing jaundice are highlighted, along with the distinction between pre-hepatic and post-hepatic causes.
π Understanding Jaundice Causes Through LFTs
The paragraph discusses using liver function tests (LFTs) to determine the cause of jaundice. It differentiates between pre-hepatic causes, such as increased red blood cell destruction or enzyme sluggishness, and post-hepatic causes, like blockages leading to cholestasis. The importance of bilirubin ratios in diagnosis is stressed, with high total to direct bilirubin ratios suggesting pre-hepatic issues and vice versa for post-hepatic causes.
π Investigating Cholestasis and Hepatocellular Injury
This section examines cholestasis, a post-hepatic condition where bile excretion is obstructed, leading to bile acid accumulation and increased ALP and GGT levels. The non-specific nature of ALP is noted, requiring GGT confirmation for liver origin. The paragraph also explores hepatocellular injury, focusing on AST and ALT enzymes, their release from liver cells, and the implications of their levels and ratios in diagnosing acute and chronic liver conditions.
π Conclusion on Liver Function Test Analysis
The final paragraph wraps up the discussion on liver function tests, summarizing the implications of abnormal levels of liver enzymes and substances. It touches on the effects of hepatocellular injury on albumin production, clotting factors, and bilirubin processing, leading to clinical manifestations like increased clotting time and jaundice. The video aims to provide a clear understanding of why LFTs are ordered and how to interpret their results to assess liver health.
Mindmap
Keywords
π‘Liver Function Tests (LFTs)
π‘Aspartate Transaminase (AST)
π‘Alkaline Phosphatase (ALP)
π‘Gamma Glutamyl Transferase (GGT)
π‘Albumin
π‘Prothrombin Time
π‘Bilirubin
π‘Jaundice
π‘Cholestasis
π‘Hepatocellular Injury
π‘Hemochromatosis
Highlights
Definition of liver function tests as blood biomarkers indicating liver function issues.
Introduction of enzymes AST, ALT, ALP, and GGT as indicators of liver injury.
Explanation of liver-produced products like albumin, prothrombin time, and bilirubin.
Reasons for ordering liver function tests, including liver disease history or concerns.
The role of liver function tests in investigating jaundice and its causes.
Importance of bilirubin levels in diagnosing jaundice and its potential causes.
Description of the liver lobules and their function in blood filtration and bile secretion.
Process of bilirubin metabolism and its conversion to direct bilirubin by the liver.
Differentiation between pre-hepatic, intra-hepatic, and post-hepatic causes of jaundice.
Use of bilirubin ratio to identify pre-hepatic causes of jaundice.
Identification of cholestasis through increased ALP and GGT levels.
Differentiation of hepatocellular injury using AST and ALT levels.
Impact of alcohol on AST levels and its distinction from ALT in cases of liver injury.
Explanation of how chronic liver conditions affect albumin, clotting factors, and bilirubin processing.
Distinguishing between acute and chronic liver injury based on AST and ALT levels.
Clinical significance of liver function tests in diagnosing and monitoring liver health.
Practical application of liver function tests in identifying liver disorders and guiding treatment.
Transcripts
hi i'm dr matt and welcome to this video
on liver function tests also known as
your liver chemistries in this video
we'll firstly define what these tests
are
secondly we'll look at some examples of
why they may be ordered and then thirdly
we'll go through a schematic drawing to
try to categorize and make sense why
these may be deranged
so starting with the definition so the
liver function tests are basically blood
parameters blood biomarkers that give an
indication that liver may not be
functioning as well as it should be so
some examples that we'll go through
firstly these are enzymes that are
released from the liver
number one in no order we have one
that's called ast
so that's aspartate transaminase
alanine transaminase
a lp
alkaline phosphatase
ggt
gamma gluta transferase now these are
all enzymes so that will give an
indication if these are markedly
increased there could be a possibility
that liver is injured and releasing
these as a result the next three are
actually products that are produced by
the liver so we have albumin
which is a protein
we have prothrombin thyme which is an
indication of the clotting factors that
are released from the liver
and then lastly we have bilirubin
which is
something that's made outside the liver
but the liver conjugates it to allow it
to be excreted so these four first four
are enzymes these are more to do with
how the liver is functioning or working
because albumin is made there the
clotting proteins are made in the liver
and the bilirubin is processed and
conjugated in the liver so if these are
outside their range it indicates that
the liver isn't functioning whereas
these enzymes indicate it might be
diseased or injured
so moving on to why
may they be ordered firstly
to look at maybe the patient has a
history of liver disease or you are
concerned that there might be a problem
so for instance if the patient comes
with jaundice this is a yellow
discoloration you may want to have an
exploration to figure out why it's
caused so you might have a look at this
panel
you may be concerned that they've taken
a medication so they've taken a poison
or something that could cause liver
injury hepatotoxic medications such as
paracetamol
in america this is acetaminophen or
tylenol but in australia we call it
paracetamol
the patient may have a history of
alcohol use
or they may have a positive family
history of so a known family history of
something that may cause damage to the
liver an example is
hematochromatosis which is basically the
way that iron is stored in the liver or
elsewhere in the body and that can cause
damage and disease to the liver
next we might look at groups that are
high risk so it's a screening tool for
patients that may be in a high risk
category this could be if they've had a
transfusion
a blood transfusion
they've been exposed to
viral hepatitis let's say
or maybe they
have used illicit drugs
now moving to another cause this could
be extra hepatic so this big certain
things that are outside the liver that
could impact the liver so examples here
would be malignancy
so this is cancer so cancer a common a
place where the cancer can spread as
secondary so this is metastasizing it
can go to the liver which then would
suggest that the liver will start to
become dysfunctional and these may start
to increase another example if the liver
has been
hypoxic so a low level of oxygen low
level of blood flow so
let's say shock a patient has a history
of shock
and therefore you're concerned that
liver might be damaged through ischemia
or hypoxic
finally medication there might be
certain medications that might cause
injury so you want to get a baseline
before you prescribe this medication
examples could be methotrexate as i said
paracetamol or vaporate so these are
some examples so there you have it there
are there are some reasons why a
clinician might order lft is to get an
idea of what is happening at the liver
now we're going to have a look at that
schematic
diagram to again to break this down and
make sense of them
now we move to the third part of this
video which is trying to make sense of
why these numbers why the liver function
tests may be out of range what i want to
look at is if your patient has jaundice
how can we figure out what is the cause
of the jaundice by looking at the lfts
and then finally the two biggest causes
of the derangement of lfts cholestasis
which means a problem with the way the
bile is leaving the liver and being
excreted or hepatic cellular injury
which means there's a problem intrinsic
to the liver itself
so let's start with jaundice jaundice is
a yellow discoloration of the skin the
sclera the mucous membranes which is due
to a buildup of bilirubin so the lft
we're going to look for here is
bilirubin
okay and basically anything above 1.2
milligrams per deciliter or per 100 ml
now before we go on we just got to
quickly make sense of where does
bilirubin come from
so bilirubin is the breakdown product of
red blood cells red blood cells will
last approximately 120 days once they
get to that age they get destructed and
killed within certain organs like the
spleen the bone marrow or the liver
themselves now when the red blood cell
is broken down
a lot of the parts will be recycled the
iron gets taken back to the liver to be
reformed into other constituents
the protein the globulins will get made
into amino acid pools but the heme
component will get broken down
phagocytosed by macrophages and
essentially be made into bilirubin
now i'm not going to go through all the
steps
mike has done a video on this so i
encourage you to have a quick look at
that if you haven't covered this before
but the bilirubin in this case will what
we call b
unconjugated bilirubin which means it
has to be carried
with a protein called albumin so that's
a complex that will get transported in
the blood and taken to the liver
before i get to the more detail what i
want to draw your attention to is this
histological unit of the liver there's
about a million of these and these are
called the liver lobules the liver
lobules are these kind of hexagonal
shaped
sections of the liver that has in the
center what we call a central vein which
is the accumulation of blood that has
diffused or percolated through all the
hepatocytes and then all of this central
vein blood will eventually accumulate
and then leave the liver via the
inferior vena cava
but what blood does it receive well it
gets arterial blood so about 20 percent
of arterial blood
is what goes through this lobule and the
70 to 80 of blood is through the portal
vein so those two bloods merge together
as the sinusoid kind of go through these
plates of cells called the parasite and
what goes the opposite direction is the
bile cannuculi which is like a river of
bile that goes out towards the outer
part of the lobule and all of these bile
ducts will start to come together
form the hepatic ducts which then become
the common hepatic duct meets the cystic
duct of the gallbladder and then we have
the common bile duct that goes down to
the duodenum
so it's this unit that i want to refer
you to specifically just one hepatocyte
so just one of those black dots will
focus in here now so this is one
hepatocyte
on the outside so this is the sinusoid
so this is the combination of portal
blood and
arterial blood fuse in through
the hepatocyte will grab things
and metabolize and filter and
do all the different functions that the
liver cells does and everything it
doesn't want it gets put into the bile
conuculide to be excreted out of the
liver but we're focusing on bilirubin
here so bilirubin will be coming along
in the systemic blood remember it's
unconjugated so it's got albumin
attached to it it gets transported
across into the hepatocyte where the
abdomen detaches and then this
unconjugated bilirubin gets taken to an
enzyme called uridine diphosphate
glucosyl transferase or ugt what this
enzyme essentially does it will add a
group to it to make it lipid sorry to
make it water-soluble this now makes it
a conjugated bilirubin
also known as
direct bilirubin so we'll focus on db
direct bilirubin from here this
conjugated bilirubin can get
excreted via a protein called mrp2 and
be put into the bile where it gets
excreted
eventually leaving the liver
as the bile duct goes down into the
intestines where a lot of it will be
metabolized by bacteria
some of it metabolized in a way that it
can be reabsorbed in the bowel with some
of it coming back
absorbed it back across and it does this
big long loop
the rest of it will get taken and put
out into the faeces that's what gives
the brown coloring some of it will
continue on as conjugated bilirubin
which can then get
urinated out and then that can be
cleared as well and the rest will just
go in this cycle
so now with that basis we need to figure
out well what could cause the bilirubin
to be increased
so this first part if your patient comes
to you with that yellowness you don't
really know what the cause and if you
were to do
some of the lfts and just find that
their bilirubin is high you still don't
know what's causing it so let's try to
figure some of this out
the first category of causes is
something that's causing an increasing
amount of red blood cell destruction and
this is what we call pre-hepatic
so if you were to have a patient that
has high amounts of red blood cell
destruction so they've got some kind of
anemia hemolytic anemia or some kind of
problem with their um hemoglobin that
could cause an increase in destruction
that would increase the amount of
hemoglobin coming for bilirubin coming
to the liver or they may have a lot of
hemorrhage hematoma that would also
increase it but another thing that could
increase it is this enzyme could be
slightly
sluggish it's not working as quickly as
it could
the common condition that that could
lead to or could lead to that decrease
in activity is gilbert syndrome so if
you have that syndrome the patient has
that syndrome this is not working so
well so therefore the conjugation speed
is going to be decreased and then you'll
have a up in the uncon unconjugated so
if you want to figure out whether
they've got a pre-hepatic cause
of their jaundice what you will do is
you do a blood test and if you see that
their total bilirubin is proportionally
higher
than their direct
so these two should be in a ratio but if
this one goes much higher to this one it
would suggest that
there's a problem pre-hepatically so it
could be increased destruction or a
problem with this enzyme
now
the other option
now there is intra-hepatic causes but
i'm going to leave it to kind of this
part so
if there's a problem with his excretion
okay that would mean that
the same the right amount of bilirubins
come to the liver the liver is doing
everything it's supposed to do it
conjugates it spits it out into the into
the bio caniculide but there's a problem
downstream there's a blockage for some
reason which means we go backwards so
the bile builds back up that means the
conjugated bilirubin comes back across
and spills across into the blood and
then we see it in the blood okay but
with this post-hepatic cause
in comparison to the pre-hepatic cause
what we actually see is an increase in
the direct
proportionally to the total
so it switches
with the pre so the post hepatic so if
it's a post hepatic cause
you'll actually see a much higher amount
or percentage of the direct
in the total because you've conjugated
it you've gotten rid of it but it's come
back and then it's gone across into the
blood okay so this is one way you can
figure out
what is leading to the jaundice
and so as we said this is a post-hepatic
cause which is essentially going to be
the collostasis which we're going to go
through now so the the remaining part of
your lfts
is to try to figure out is the cause due
to a cholestasis so a problem with the
excretion or a problem with the cell
itself
so let's have a look at this one to
start with
so let's assume that there is a blockage
so there could be a stone
in the bar duct or there could be a
structure so it's narrowed or there
could be a tumor down in the head of the
pancreas
causing the flow to be disrupted in any
case the bi will come backwards so it
will come back up and what you'll see is
the bile acid will come across
back into the hepatocyte
now
on the membrane the bile the biconicular
side of the hepatocyte so this side of
the membrane there is an enzyme here
that can produce
a number of other
and
what this is going to be
is
alp so that's the alkaline phosphatase
and this is generated by that enzyme on
that membrane so when it's exposed to
increased amount of bile acid this
enzyme will become more active which
increases the alp which then is pushed
across into the sinusoid which then goes
into the central vein and the ivc and
then in your blood so if you start to
see an increase in alp
so let's say you do your alp levels and
you've got a big increase or two two
arrows up of alp
you have a suspicion that it's due to a
cholestasis cause
but an important point here is alp
is not specific to the liver it's also
found in the placenta it's also found in
bone tissue so you need to be sure that
it is actually from the liver so there's
another enzyme that kind of works on
that membrane as well and that's the g
g t that's the gamma gluta transferase
so you want to also look for that one
and if that is also up which is kind of
the same mechanism you'll see that one
up as well and if you see ggt up with
alp you are confident that it's
a cholestasis cause particularly if your
direct bilirubin is up as well okay now
for whatever reason let's just say your
alp was up but this was normal and there
was nothing here
you need to suspect that it's coming
from somewhere else outside the liver
for instance
bone is a big one so osteoblasts when
they're highly active they're releasing
this enzyme so this could be recent
fractures or certain conditions where
there's maybe tumors in the bone or
pages disease causing an increase in ap
levels
finally we're going to have a look at
hepatocellular injury so i'll just clear
this off quickly
and the two big enzymes that you need to
be aware of with a paracellular injury
is ast
and a l t
an important thing just to remember
the s here
even though these are found in the liver
the s
the way i remember is also striated
muscle so this can be found in cardiac
muscle and skeletal muscles so it's not
specific to the liver so sometimes
problems with heart or or spleeder
muscles could also increase ast so just
be aware of that but the alt-l is
specific l to liver so this is much more
specific to liver
in terms of asp
asd the majority that 80 is found in the
mitochondria
whereas the majority of alt is found out
in the cytoplasm just to reiterate that
ast 80 is found in the mitochondria 20
in the cytoplasm whereas the majority of
the alts in the actual hepatocyte
cytoplasm itself in terms of the ratio
there's more ast in the cell than alt
but this is
diffused out quicker which means in the
blood these two are about a one to one
ratio so if you would a
normal person and normal
levels of these two they're about a one
to one ratio
okay so we've understood that ast and
alt is more specific to the hepatocyte
injury okay but how do we distinguish
with what kind of injury well if the
numbers are kind of above
10 times what they normally are that's
an indication that there is an acute
injury
and it's
severe
so this is inflammatory based so
anything that's kind of causing
hepatocell inflammation acutely and
quite severely is going to raise the
amount of these two
significantly this could be due to
paracetamol so the toxic effects a viral
acute viral infection like hepatitis or
hypoxic injury like there's not enough
blood coming to the liver which is going
to cause extreme inflammation causing
these levels to go up a significant
amount so this is more acute
causes of liver injury if the number is
only let's say five
times increased it's more suggestive
that it's a chronic effect
okay so chronic effects this could be
things like
fatty liver which could be
alcohol-based or non-alcohol based fatty
liver a chronic viral hepatitis
or certain medications over time
it's important to distinguish though
that ast
seems to be more sensitive to alcohol
the reason well the theory for why that
could be
is a combination of ethanol
causes irritation to the mitochondria
which causes it to spill out and go into
the blood at a higher amount so the
ast like we said it should be one to one
it's a higher ratio with alcohol-induced
injury so the ast could be higher or the
other cause of ast being increased
relative to alt is through more chronic
fibrosis or cirrhosis that causes the
flow the blood flow through the liver to
be sluggish which then reduces the
amount of ast that normally leaves which
then increases its buildup so
ast
increased relative to alt in ratio is
usually due to cirrhosis
and alcohol
finally
because the hepatocyte in the
hepatocellular injury they're not it's
not functioning as well you're going to
see those certain parameters like
albumin album has been isn't being
produced to its normal level same with
the clotting proteins and also the way
that the
bi the way that the bilirubin is
processed through the hepatocyte it's
going to be diminished and they're going
to see the changes a reduction in
abdomen problems with clotting time so
the clotting time increases and we see
problems with the bilirubin processing
that's outside pre-hepatic and
post-hepatic if there's a problem
intrinsic to the cell with the enzymes
and the transport proteins that's going
to play around with bilirubin secretion
excretion as well
so hopefully today you've seen
what liver enzymes are what are the
indications of why they will be ordered
and then we've schematically moved
through to try to make sense why each
one of them may be increased or deranged
outside their normal values
Browse More Related Video
5.0 / 5 (0 votes)