ASSESSMENT
OF LIVER
FUNCTIONS
OBJECTIVES
By the end of this tutorial, students
should be able to :
➢ Describe the main functions of liver.
➢ Outline the components of liver function tests
(LFT) and their clinical use.
What is the liver?
Liver is the largest and most complex organ of
the body.
It is usually contributing 1/50 of the entire body
weight (1400-1600 g) in adults, and a much
larger proportion (about 1/20) in the newborn.
It is a meaty organ that sits on the right side of
the abdomen. The liver is reddish-brown in color
and feels rubbery to the touch.
The liver has two large sections, called the right
and the left lobes. The gallbladder sits under
the liver, along with parts of the pancreas and
intestines. The liver and these organs work
together to digest, absorb, and process food.
[Link]
post/2017/09/29/Loving-The-Liver
Functions of the Liver
The liver's main job is to filter the blood
coming from the digestive tract (hepatic
portal vein), before passing it to the rest of
the body (it is called body gate to get rid of
toxins), moreover liver functions can be
classified into :
1-Metabolic Functions
2-Excretory Functions
3-Protective functions & detoxification
4-Hematological and synthetic functions
5-Storage functions
1-Metabolic:
Carbohydrate metabolism( glucose homeostasis),
lipid, protein, mineral and vitamin metabolisms.
Destruction of erythrocytes (Bilirubin)
Metabolism of most drugs to be excreted through
urinary system
Activation of pro-drugs
2-Synthetic: plasma proteins (albumin)
,coagulation proteins (prothrombin , I, II, V, VII-XIII),
specific binding proteins (transferrin , ceruplasmin )
3-Storage: Glycogen, iron, copper, fat soluble
vitamins (K,E,D,A) and B12
4-Protective functions: Kupffer cells of liver
perform phagocytosis to eliminate foreign compounds,
and xenobiotic.
5-Detoxification : liver convert toxic ammonia into
urea via urea cycle .
6-Excretory: Bile pigments, bile salts and are
excreted through bile duct in to the intestine.
7-Manufacturing of triglycerides, and cholesterol.
Liver Conditions
Hepatitis: Inflammation of the liver, usually caused
by viruses like hepatitis A, B, and C. Hepatitis can
have non-infectious causes too, including heavy
drinking, drugs, allergic reactions, or obesity.
Fatty liver (Steatosis): Steatosis is accumulation of
neutral fat in liver cells.
Although the fat in the liver usually posses no harm,
it can lead to inflammation of the liver
(Steatohepatitis)
Fibrosis: Is the excessive accumulation of
extracellular matrix proteins including collagen that
occurs in most types of chronic liver diseases, with
the replacement of healthy tissue with fibrous
tissue.
Cirrhosis: Long-term damage to the liver
characterized by replacement of liver tissue by
fibrous, scar tissue and regenerative nodules
leading to irreversible loss of liver functions.
Liver cancer: The most common type of liver
cancer, hepatocellular carcinoma, almost always
occurs after cirrhosis occurs.
Ascites: As cirrhosis occurs, the liver leaks fluid
(ascites) into the belly, which becomes
distended and heavy.
Jaundice: It refers to yellowish appearance
of the Skin, Sclera and Mucous membranes.
How to diagnose liver diseases?
1-Clinical examination (signs , symptoms) and
taking patient history.
2-Evaluation of liver functions via:
Imaging Tests:
➢ Ultrasound: An abdominal ultrasound can test for many
liver conditions, including cancer, cirrhosis, or problems
from gallstones.
➢ Computed Tomography (CT) scan : A CT scan of the
abdomen gives detailed pictures of the liver and other
abdominal organs.
➢ Liver biopsy : A liver biopsy which is most commonly
done after other tests, such as a blood test or
ultrasound, indicates the possible liver problem.
Blood Tests(liver function panel)
Liver Function Panel
A liver function panel are useful for :
1-Checking how well the liver is working.
2-Detecting the presence of liver disease.
3-Placing the liver disease in the appropriate
broad diagnostic category. This then allows the
selection of further, more expensive and time-
consuming investigations such as computed
tomography (CT) scanning, endoscopy and liver
biopsy.
4-Following the progress of liver disease.
Liver Function Panel cont.
The following tests are commonly used for diagnosis
of liver diseases :
I- Aminotransferase measurements (ALT & AST):
The measurement of the activity of ALT & AST in plasma
provides a sensitive index of hepatocellular damage.
Plasma ALT measurement is more liver-specific than AST.
II- Lactate dehydrogenase:
Lactate dehydrogenase (LDH) activity, especially LD5 is an
enzyme found in the liver. Elevated levels may indicate
liver damage but can be elevated in many other disorders.
III- Alkaline phosphatase (ALP)
The term "serum ALP" is applied to a group of
enzymes that catalyze hydrolysis of phosphate
esters at an alkaline pH.
The enzymes are widely distributed and may
originate from bone, liver, intestine, kidney, or
placenta.
They are normally attached to the biliary
canaliculi. For this reason, they are released in
much greater amounts when there is cholestasis.
IV- Gamma Glutamyl Transpeptidase (GGT)
GGT is present in the cell membranes of many tissues,
including the kidneys, bile
duct, pancreas, gallbladder, spleen.
GGT is predominantly used as a diagnostic marker for
liver disease
Plasma GGT has the advantage of being more liver-
specific than plasma ALP, because the latter is also
increased in case of bone disease.
Moreover, in children and adolescents, in whom bone
growth is active, serum ALP may also increase by up to
threefold.
V- Serum proteins:
The measurement of certain plasma proteins
provides an index of the liver's ability to synthesize
protein or not.
1-Albumin: In chronic hepatocellular damage,
there is impaired albumin synthesis with an
accompanying fall in plasma albumin. Albumin
measurements provide a fairly good index of the
progress of chronic liver disease. In acute liver
disease, however, there may be little or no
reduction in plasma albumin, as the biological half-
life of albumin is about 20 days.
2-Coagulation factor:
In liver disease, the synthesis of prothrombin and
other clotting factors is diminished, leading to an
increased prothrombin time (PT) and Partial
ThromboplastinTime (PTT). This may be one of the
earliest abnormalities seen in patients with
hepatocellular damage, since prothrombin has a short
half-life (approximately 6h).
3-Immunoglobulins:
Plasma Igs measurements are of little value in liver
disease because the changes are of low specificity. In
most types of cirrhosis, plasma IgA(mucosal
homeostasis) is often increased, while in primary
biliary cirrhosis, plasma IgM increases greatly. In
chronic active hepatitis, plasma IgG tends to be most
increased.
VI- Serological tests:
Viral antigens and antibody measurements
are important in detecting infective causes of
liver disease (Hepatitis A antibody, Hepatitis B
antibody and Hepatitis C antibody)
VII- Hyaluronic acid (hyluronin):
Hyaluronic acid is studied as a non-invasive
marker of liver fibrosis in chronic liver diseases,
in an attempt to avoid the complications of liver
puncture biopsy, considered the gold standard in
the evaluation of fibrosis..
VIII- Serum bilirubin:
Hepatobiliary disease is indicated when the
conjugated fraction of total bilirubin exceeds
the upper limit of normal.
The presence of conjugated, water-soluble
bilirubin in the urine (bilirubinuria) always
indicates hepatobiliary disease.
Hemolysisand Gilbert syndrome are common
conditions that cause benign elevation of
unconjugated bilirubin.
Normal blood test results for typical liver
function tests include:
Liver function test Value
ALT. 7 to 55 units per liter (U/L)
AST. 8 to 48 U/L
ALP. 45 to 115 U/L
Albumin. 3.5 to 5.0 grams per deciliter (g/dL)
Total protein. 6.3 to 7.9 g/dL
Bilirubin. 0.1 to 1.2 milligrams per deciliter
(mg/dL)
GGT. 9 to 48 U/L
LD. 122 to 222 U/L
PT. 9.5 to 13.8 seconds
Determination of aminotransferases:
Why Are AST and ALT Useful?
Because these enzymes are found in liver cells
(hepatocytes), which have lots of contact with
your blood supply, so AST and ALT can "leak" into
the blood if the hepatocytes are damaged.
Abnormally high levels of both liver enzymes
show that liver cells have been damaged, but
they can't tell what caused the damage.
Aspartate aminotransferase, or AST, is found in the
liver, but also in the brain, pancreas, heart, skeletal
muscle, kidneys, and lungs with the highest
concentration in heart compared with other tissues
of the body
AST exists in two different isoenzyme forms which
are genetically distinct, the mitochondrial and
cytoplasmic form.
About 80% of AST activity of the liver is contributed
by the mitochondrial isoenzyme.
Aspartate transaminase catalyzes the interconversion
of aspartate and αketoglutarate to oxaloacetate and
glutamate
Aspartate (Asp) + α-ketoglutarate oxaloacetate +
glutamate (Glu)
Alanine aminotransferase, or ALT, is primarily found
in the liver.
ALT is purely cytoplasmic.
Alanine transaminase catalyzes the interconversion
of alanine and αketoglutarate to pyruvate and glutamate
AlT test is more
specific and sensitive
than AST test
However, a disease cannot be diagnosed by the pattern of
elevation alone. The magnitude of elevation also needs to
be evaluated. Among the examples:
With alcoholic fatty liver disease, the AST would
generally be more than eight times the ULN (Upper
Limits Of Normal) and the ALT more than five times the
ULN.
With non-alcoholic fatty liver disease, the AST and ALT
would both be more than four times the ULN.
With acute viral hepatitis, the AST and ALT would both
be 25 times the ULN.
With chronic hepatitis C, the AST and ALT could be
anywhere from two to 10 times the ULN.
With ischemic hepatopathy (also known as shock liver),
the AST and ALT would be over 50 times the ULN
AST/ALT ratio
The ratio of AST to ALT has more clinical utility
than assessing individual elevated levels.
Ithas been suggested that the relative activities
of AST to ALT give some index of the underlying
pathology and severity of the disease processes.
For example, in hepatitis, acute hepatocellular
injury the ALT level is usually greater than that
of the AST; if the AST is found to be greater than
that of ALT it suggest that there is widespread
hepatic necrosis (release of mitochondrial
enzymes)
Here are some common guidelines used for liver
disease:
An AST:ALT ratio equal to one (the level of ALT
is higher or equal to AST), but the levels are
very high, suggests acute viral hepatitis or
drug-related hepatitis.
An AST:ALT ratio higher than one (where the
level of AST is higher than the ALT) could also
indicate cirrhosis.
An AST:ALT ratio higher than 2:1 (the level of
AST is two times that of ALT) is very suggestive
of alcoholic liver disease.
1- Determination of Serum Alanine
Aminotransferase (ALT)
Principle (colorimetry)
GPT catalyzes the following reaction:-
ALT
Oxoglutarate + L-alanine L-glutamate +
pyruvate
The pyruvate formed reacts with 2, 4
dinitrophenyl hydrazine in alkaline solution to
give the dinitrophenyl hydrazone [Link]
produced brownish colour is measured at 540 nm.
Procedure
Bring two dry test tubes , first for the test
sample & the second for blank.
Pipette 0.25ml of ALT(GPT) buffered substrate
(reagent 1) into each test tube .
Add 0.1ml of sample (serum or plasma) to
first tube & 0.1ml of dist. Water to the
second tube
Mix, incubate for 30 minutes exactly at 37OC.
Add 0.25 ml of 2, 4-dinitrophenylhydrazine
(reagent 2) to both tubes.
Mix, incubate for 20 minutes exactly at 25OC.
Add 0.25 ml of NaOH to each tube.
Mix & waits for 5 min then read absorbance of
sample against blank at 540 nm.
Calculation:
Results are read from standard tables or curves
Absorbance 0.025 0.05 0.075 0.1 0.125 0.15
Activity (IU/L) 2 5 9 12 16 20
Direct
relationship
between ALT
activity &
Absorbance