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The liver is the largest organ in the


body
It is located below the diaphragm
in the right upper quadrant of the
abdominal cavity and extended
approximately from the right 5th rib
to the lower border of the rib cage.
The liver is separated into a right
and left lobe, separated by the
falciform ligament. The right is
much larger than the left .

The
liver
performs
thousands of tasks that
impact all body systems.
Liver have two channels
that can supply and oxygen
nutriment : hepatic artery
and hepatic portal vein .
The
corresponding
channels is hepatic vein
and bile ducts.

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The working cells of the liver are


known as hepatocytes, which have a
unique capacity to reproduce in
response to liver injury.
Liver regeneration can occur after
surgical removal of a portion of the
liver or after injuries that destroy
parts of the liver.
Although the liver's ability to react
to damage and repair itself is
remarkable, repetitive insults can
produce liver failure and death.

Functions of liver
Excretory function: bile pigments,
bile salts and cholesterol are excreted in
bile into intestine.
Metabolic function: liver actively
participates in carbohydrate, lipid,
protein,
mineral
and
vitamin
metabolisms.
Hematological function: liver is also
produces clotting factors like factor V,
VII. Fibrinogen involved in blood
coagulation is also synthesized in liver.
It synthesize plasma proteins and
destruction of erythrocytes.

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Storage
functions:
glycogen, vitamins A, D and
B12,and trace element iron
are stored in liver.

Protective functions and


detoxification: Ammonia is
detoxified to urea. kupffer
cells
of
liver
perform
phagocytosis to eliminate
foreign compounds.

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What is Purpose of LFTs?


LFTs alone do not give the
physician full information,
but used in combination
with a careful history,
physical
examination
(particularly ultrasound and
CT
Scanning),
can
contribute to making an
accurate diagnosis of the
specific liver disorder.

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liver function tests


1. Detect the presence of liver disease
2. Distinguish different types of liver
disorders
3. Extent of liver damage
4. Follow the response to treatment
A. Can be normal in serious liver
disease
B. Can be abnormal in non hepatic
diseases
C. Rarely suggest a specific diagnosis
D. They suggest a general category of
liver disease, such as hepatocellular
or cholestatic

LFTs are divided into


True tests of liver function,
such as serum albumin,
bilirubin, and prothrombine
time,
Tests that are indicators of
liver injury or biliary tract
disease.

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Classification of liver functions test


Excretion: Measurement of

bile

pigments, bile salts.


Serum enzymes: Transaminase (ALT,
AST), alkaline phosphate(ALP), 5nucleotidase, LDH isoenzyme.
Synthetic function: Prothrombin time,
serum albumin.
Metabolic

capacity:

Galactose

tolerance and antipyrine clearance


Detoxification: Serum ammonia

Excretion : Bilirubin
Bilirubin is the main bile
pigment that is formed
from the breakdown of
heme in red blood cells.
The broken down heme
travels to the liver, where it
is secreted into the bile by
the liver.

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BLOOD
CELLS

Stercobilin
excreted in feces

Hemoglobin

Urobilin
excreted in urine

Globin
Urobilinogen
formed by bacteria

Heme
O2
Heme oxygenase

INTESTINE

reabsorbed
into blood

KIDNEY

CO
Biliverdin IX

via bile duct to intestines

NADPH
Biliverdin
reductase

Bilirubin diglucuronide
(water-soluble)

NADP+

2 UDP-glucuronic acid

Bilirubin
(water-insoluble)

via blood
to the
liver

Bilirubin
(water-insoluble)

LIVER

Metabolism of bilirubin

1. Serum Bilirubin:
Normally, a small amount of bilirubin circulates in the blood.
Serum bilirubin is considered a true test of liver function, as it reflects
the liver's ability to take up, process, and secrete bilirubin into the bile.

A. Indirect bilirubin
(normal value = 0.3 - 1.2 mg/dl)

B. Direct bilirubin
(normal value 0.4 mg/dl)

C. Total bilirubin
Normal value for = 0.3- 1.2 mg/dl.

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Difference of two bilirubins


Indirect
bilirubin
Binding with
Glucuronic acid
Reacting with the diazo
reagent

no

Direct
bilirubin
yes

Slow and
indirect

Rapid and
direct

small

large

Discharged via kidney

no

yes

Pass through the


membrane of cell

yes

no

Pass blood brain


barrier

yes

no

solubility in water

2. Urine & Stool


Urobilinogen :
Conjugated bilirubin is excreted via
bile salts to intestine.
Bacteria in the intestine break down
bilirubin to urobilinogen
for
excretion in the feces (normal value
for fecal urobilinogen = 40 - 280
mg/day)
Normally there are mere traces of urobilinogen in the urine. average is
0.64mg , maximum normal 4mg/24hours.

Urobilin
Urobilin is the final product of oxidation of urobilinogen by oxygen in
air. The amount change with the amount of urobilinogen excretion .

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Bilirubin urine:
Bilirubin is not normally present in
urine and faese since bacteria in intestine
reduce it to urobilinogen.
The kidneys do not filter unconjugated
bilirubin because of its binding to albumin.
Conjugated bilirubin can pass through
glomerular filter.
Bilirubin is found in the urine in
obstructive jaundice due to various causes
and in cholestasis.
Bilirubin in the urine may be detected
even before clinical jaundice is noted.

Who is a candidate for the test?


Bilirubin is used to diagnosis of jaundice.
Abnormal bilirubin levels can be found in
many disorders, including:
Hemolytic Jaundice
Hepatic Jaundice
Obstructive jaundice ( Cholestasis)
Congenital Jaundice

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Sample

Indices

Hemolytic
Jaundice

Hepatic
Jaundice

Obstructive
Jaundice

Serum

Total Bil

1mg/dl

1mg/dl

1mg/dl

Direct Bil

Urine

Stool

Indirect Bil

Color

deeper

deep

deep

Bilirubin

Urobilinogen

uncertain

Urobilin

uncertain

Color

deeper

lighter or
normal

Argilous
(complete
obstruction)

Aproach to isolated elevation of


bilirubin

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Aproach familial elevation of


bilirubin

Familial hyperbilirubinaemia , Congenital hyperbilirubinaemia

Degree of elevation of bilirubin


Not as a prognostic marker
But is important in :
1. Viral hepatitis: higher bilirubin
greater hepatocellular damage.
2.Alcoholic hepatitis: total serum
bilirubin correlates with poor outcomes
3.Component of the model for end stage
liver disease (MELD)
4.Drug-induced liver disease: elevated
total serum bilirubin indicates more
severe injury.

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Serum Enzymes
The liver contains thousands of enzymes
These enzymes have no known function
probably cleared by reticuloendothelial cells
liver cells damage entrance of Enzymes into serum

3 type of Liver enzyme tests


1. Enzymes whose elevation reflects damage to
hepatocytes
2. Enzymes whose elevation reflects cholestasis
3. Enzyme tests that do not fit either pattern.

Enzymes that Reflect


Damage to Hepatocytes
Aspartate aminotransferase
(AST)
= serum
glutamic oxaloacetic transaminase (sGOT)
Alanine aminotransferase (ALT) = Serum glutamic
pyruvic transaminase (sGPT)

Sensitive indicators of liver cell injury


Most helpful in recognizing acute hepatocellular
diseases (hepatitis)

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Alanine transaminase (ALT)


GPT

Aspartate aminotransferase (AST)


GOT

AST ( sGOT) is found in


Liver
Cardiac muscle
Skeletal muscle
Kidneys
Brain
Pancreas
Lungs
Leukocytes, and
erythrocytes

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organ

GOT

GPT

organ

GOT

GPT

heart

156000

7100

pancrease 28000

2000

liver

142000

44000

spleen

14000

1200

skeletal 99000

4800

lung

10000

700

kidney

19000

20

16

91000

GPT:
Normal range: 2-59 U/L

serum

GOT:
Normal range: 10-34 U/L

Therefore, when the liver is injured, GPT is


released into the bloodstream.

sGOT also reflects damage to the hepatic


cells and is less specific for liver disease. It
can also be released with heart, muscle and
brain disorders.
Therefore, this test may be ordered to help
diagnose various heart, muscle or brain
disorders, such as a myocardial infarct .

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Alcoholic liver disease


Cancer of the liver
Cholestasis or congestion of the bile ducts
Cirrhosis or scarring of the liver with loss of
function
Death of liver tissue
Hepatitis or inflammation of the liver
Noncancerous tumor of the liver
Use of medicines or drugs toxic to the liver

Acute hemolytic anemia,


Acute pancreatitis or inflammation of the pancreas.
Acute renal failure or loss of kidney function.
Cirrhosis of the liver.
Hepatitis
Heart attack
Primary muscle disease
Recent surgery
Severe burns
Muscle injury

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Levels of aminotransferases
<300 U/L are nonspecific and may be found in any
type of liver disorder.

Minimal ALT elevations


Asymptomatic blood donors
Severe liver disease
Fatty liver is the most cause.

Extensive hepatocellular injury such:


1) Viral hepatitis
2) Ischemic liver injury (prolonged hypotension or
acute heart failure)
3) Toxin- or drug-induced liver injury.

The pattern of the aminotransferase


Acute hepatocellular disorders: ALT AST.
Chronic viral hepatitis : ALT AST
Cirrhosis : AST ALT

AST/ALT ratio
Normal - 1 or slightly > 1
<1 : NASH or hepatitis
without cirrhosis
2-4:ALD
>4 : Wilsonian hepatitis

Causes of AST /ALT > 2


ALD
Acute wilsonian hepatitis
DDP
Metastasis
cirrhosis

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Approach to asymptomatic elevation


of serum aminotransferase

Alcoholic liver disease


AST/ALT >2:1 is suggestive
AST/ALT >3:1 is highly suggestive
The AST is rarely >300 U/L
ALT is often normal.
A low level of ALT in the serum is due to an alcohol-induced
deficiency of pyridoxal phosphate.

Obstructive jaundice
Aminotransferases not greatly elevated
Exception: passage of a gallstone into the common bile duct
acute biliary obstruction aminotransferases 10002000
decrease quickly liver-function tests rapidly evolve typical of
cholestasis.

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Enzymes that Reflect


Cholestasis
Are usually elevated in cholestasis
Alkaline phosphatase
5'-nucleotidase
Gama glutamyl transpeptidase (GGT)

Alkaline phosphatase (ALP)


ALP occurs in all tissues,
especially liver and bone.
The alkaline phosphatase
test is often used to help
diagnose
certain
liver
diseases
and
bone
disorders .
Normal range: 30 - 95
IU/L (3-13 kings unit)

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Alkaline phosphatase
ALP is a hydrolase enzyme responsible for removing phosphate
groups from many types of molecules, including nucleotides and
proteins.
Most effective in an alkaline environment
In humans it is present in all tissues throughout the entire body,
but is particularly concentrated in
Liver
Heat-stable :
Bile duct
placenta or a tumor is the source.
Kidney
Heat unstable:
intestinal, liver, and bone
Bone
The placenta.

Higher levels of ALP than normal


may indicate:
Liver disease
Bone disease
Leukemia

Lower levels of ALP than


normal may indicate:
Anemia, or a low red blood cell count
Malnutrition

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Mechanism of increase in ALP in liver disease:


Increase in the activity of ALP in liver disease is not
due to hepatic cell disruption , nor to a failure of
clearance , but rather to increased synthesis of hepatic
ALP .
The stimulus for this increased synthesis in patients
with liver disease has been attributed to bile duct
obstruction by stone ,tumors , intrahepatically by
infiltrative disorders or space-occupying lesions.

ALP Non Pathologically Elevated


Age > 60
Blood types O and B after
fatty meal (influx of
intestinal ALKP into the
blood.)
Children and adolescents
undergoing rapid bone
growth, (bone)
Late
in
normal
pregnancies (influx of
placental )

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Elevation of liver-derived alkaline


phosphatase
Not specific for
cholestasis
< 3 fold occur in :

Level
of
ALP
is not helpful in
distinguishing

Any type of liver disease.

Between intrahepatic and


extrahepatic cholestasis

>4 fold occur in:


Cholestatic liver disorders
Infiltrative liver diseases
such as cancer and
amyloidosis

Obstructive jaundice due to


cancer, common duct stone,
sclerosing cholangitis, or bile
duct stricture.

Aproach to elevation of ALP

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5' NT
Sensitive
and
specific
hepatobiliary disorders (HBD)

for

Normal pregnancy, bone growth and


bone diseases do not affect 5' NT
In pts with HBD, changes in ALP are
usually followed by similar changes
in 5' NT

GGT
Inducible microsomal enzyme.
N levels 5- 40 IU/L.
Less specific than 5' NT as a marker for
HBD
Unlike 5' NT, GGT may be released from
many sites beside the hepatobiliary tree.
Bone important source of ALP, has little
GGT thus GGT useful for differentiating
hepatic & osseous sources of ALP

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Enzymes that do not fit either pattern.

lactate dehydrogenase
This test measures the total level of the
enzyme lactic dehydrogenase, also called LDH,
in the blood.
LDH is found in body tissues and organs.

LDH isoenzymes
Tissue or organ injury can release LDH into
the bloodstream, thereby raising the level.
If he or she suspects a heart attack or liver
tissue damage in the body.
Normal range: 115-225 IU/L

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Tests based on livers function:


Carbohydrate metabolism
Lipid metabolism
Protein metabolism

Not of much value in liver diseases


It is often difficult to separate the part
played by the liver from other factors
influencing glucose metabolism.

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Basis:
For galactose is a monosaccharide, almost
exclusively metabolized by the liver.
The normal liver is able to convert galactose
into glucose.
This function is impaired in intrahepatic disease
and the amount of blood galactose and urine
galactose is excessive.
The liver can be assessed by measuring the
utilization of galactose.

It is used primarily to detect liver cell injury.


It can be performed in presence of jaundice.
As it measured an intrinsic hepatic function, it may be
used to distinguish obstruction and non obstruction
jaundice.

Method :
Oral galactose tolerance test
IV galactose tolerance test(intravenous injection )

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Result:
Normally or obstructive jaundice:
3gm or less of galactose are excreted in the urine
within 3 to 5 hours and the blood galactose returns to
normal within one hour.

Intrahepatic jaundice:
The excretion amounts to
4 to 5gm or more during
the first 5 hours.

Normal response:
Shows little or no rise in the blood sugar level.
The highest blood sugar value reached during the test
should not exceed the fasting level by more than 30 mg%.
In infectious hepatitis or
parenchymatous
liver
cells damage:
Rise in blood sugar is
greater than above, but the
increases obtained are
never very great.

//

Tests Based On Lipids Metabolism


Cholesterol-cholesteryl Ester Ratio:
The liver plays an active and important role in
the

metabolism

of

cholesterol

including

its

synthesis,esterification,oxidation and excretion.


Normal total blood cholesterol ranges from 150 ~
250mg/dl and approx 60 to 70% of this is in erterified
form.

In parenchymatous liver disease:


Their is either no rise or even decrease
in total cholesterol and the ester fraction is
always definitely reduced.
The degree of reduction roughly parallels
the degree of liver damage.

In severe acute hepatic necrosis:


The total serum cholesterol is usually
low and may fall below 100mg/dl, while
there is marked reduction in the % present
as esters.

//

Tests based on amino acid metabolism


Determination of
blood NH3:
Nitrogen part of amino
acid is converted to
NH3 in the liver mainly
by transamination and
deamination and it is
converted to urea in
liver only .

Synthetic functions
1. Total plasma proteins/ albumin/ globulin/

A:G ratio
2. Formation of prothrombin by liver

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This yields most useful information in chronic liver


disease.
Liver is the site of albumin synthesis and also
possibly of some of and globulins.
Normal value:
Total plasma proteins: 80~110mg/dl
Albumin:40-50mg/dl
Globulin:25~35mg/dl
A:G ratio: 1.5~2.5

In infectious hepatitis:
Quantitative estimations of albumin and
globulin may give normal results in the early
stages.
Qualititative changes may be present,in
early stage rise in -globulins and in later
stages -globulins shows rise.

In cirrhosis liver or parenchymal


liver disease:
The albumin is grossly dicreased and the
globulins are often increased,so that A:G ratio
is reversed, is characteristically seen in
cirrhosis liver.

//

Albumin is an important blood protein that is made


only by the liver and excreted by the kidneys.
Albumin is essential for maintaining
the osmotic pressure in the vascular
system.
low albumin level produce ascites.
Albumin is also very important in the
transportation of many substances
such as drugs, lipids, hormones and
toxins that are bound to albumin in the
bloodstream.

Synthesized exclusively by hepatocytes.


Long half-life: 1820 days
Normal range: 34 - 54 g/L
Not a good indicator of acute or mild hepatic
dysfunction (slow turnover)
This test is normally performed to assist in
diagnosing diseases that affect proteins in the
body, such as cancer, liver disease, renal or
intestinal problems, and immune disorders.

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Abnormally low contents of albumin may indicate:


Ascites
Extensive burns
Kidney disease
Liver disease
Malabsorption syndromes
Protein-losing enteropathies
Chronic infections that inhibit albumin synthesis.

Common in chronic liver disorders such as cirrhosis than


in acute liver disease
Reflects severe liver damage and decreased albumin
synthesis.

Immunoglobulins produced by B
lymphocytes
Globulins are increased in chronic
hepatitis and cirrhosis.
In cirrhosis: due to the increased
synthesis of antibodies against
intestinal bacteria.
Cause : cirrhotic liver fails to
clear bacterial antigens that
normally reach through the
hepatic circulation.

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Diffuse polyclonal IgG in autoimmune


hepatitis
IgM in primary biliary cirrhosis
IgA in alcoholic liver disease

At least 12 different proteins are involved in clotting.


Blood clotting factors are proteins made by the liver and are
associated with the incorporation of vitamin K metabolites
into a protein.
When the liver is significantly injured, these proteins are
not normally produced.
PT (Prothrombin time)
Estimation of plasma fibrinogen
APTT(activated partial thromboplastin time)

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Prothrombin is a plasma protein that is converted


into thrombin during blood clotting.
Prothrombin is formed in the liver from inactive
preprothrombin in presence of vitamin K.
in presence of vitamin K

thrombin

Prothrombin
Ca2+, PL

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Prothrombin time is measured as prothrombin activity.


The term prothrombin time was given to time required for
clotting to take place in plasma to III factor and Ca+ have
been added.
PT is used to assess the activity of extrinsic blood clotting
pathway .
PT is also a useful test of liver function, since there is a
good correlation between abnormalities in coagulation
measured by PT and the degree of liver dysfunction.
PT is usually expressed in seconds and compared to a
normal control patients blood.

This test may be done:


When a person has a bleeding problem
Monitor a person who is taking oral anticoagulants
Before surgery to make sure a person will not bleed too
much during the operation.
Prothrombin activity is also sometimes expressed as
prothrombin index, which is the ratio of prothrombin
time of the normal control to the patients prothrombin time:
PT of normal control

Prothrombin index =

x100
PT OF patient

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High PT values may occur when a person:


Is taking blood-thinning medicines like warfarin
Is taking other medicines, such as certain
antibiotics, that interfere with the test
Has severe liver disease
Has DIC :a complex blood disorder that occurs
when clotting mechanisms are activated
throughout the body
Has certain rare, inherited bleeding disorders
Has a vitamin K deficiency

Abnormally low PT values are usually not


significant.
However, they may occur when a person:
Has cancer
Has blood clots
Is taking certain medicines, such as oral
contraceptive pills

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Protective functions and detoxification

Blood Ammonia
Produced
During normal protein metabolism
Intestinal bacteria in the colon.
liver plays : detoxification of ammonia by converting it
to urea excreted by the kidneys

Striated muscle

detoxification of
(combination with glutamic acid )

ammonia

Elevated ammonia levels


Has very poor correlation with:
Presence or severity of acute encephalopathy
Hepatic function.

//

Elevated ammonia levels


Occasionally useful for occult liver disease in
mental changes.
Correlate with outcome in fulminant hepatic
failure.
In severe portal hypertension and shunting around
the liver even in normal or near-normal hepatic
function.

Some Other Tests For LFTs


Mitochondrial Antibodies Test
The presence of these antibodies can indicate primary biliary
cirrhosis, chronic active

hepatitis, and

certain

other

autoimmune disorders.

Platelet count:
In cases of chronic liver disease where cirrhosis exists, the
platelet count can be lowered although this can occur due
to many conditions other than liver disease.

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Fibrinogen
Synthesized exclusively by hepatocytes
Plasma fibrinogen 100-700 mg/dl
Functions polymerizes into long fibrin threads by the
action of thrombin formation of clot

Haptoglobins
Forms stable complexes with free Hb
prevents loss of
iron through urinary excretion, protects kidney from damage

Ceruloplasmin
Binds with copper and helps in its transport and storage

Bromosulphathein excretion test


BSP dye- same mechanism as bilirubin
Binding
Conjugation
Excretion
BSP i/v 45 mins- levels in venous blood
Normally- <5%.
Slightly higher in old age
Sensitive test to detect mild impairement of liver

Indocyanine green
This dye is removed by the liver after intravenous injection. A
blood level is obtained 20 min after administration.
Compared with BSP its hepatic clearance is more efficient, and
it is nontoxic.

//

Serum bile acids


Synthesized from cholesterol in the liver, conjugated to
glycine or taurine, and excreted in the bile.
Bile acids facilitate fat digestion and absorption within the
small intestine. They recycle through the enterohepatic
circulation.
Detection of an elevated level of serum bile acids is a
sensitive marker of hepatobiliary dysfunction
A number of different bile acid tests have been described,
including fasting and postprandial levels and determination of
levels after a bile acid load.
Normal bile acid levels in the presence of
hyperbilirubinemia suggests hemolysis or Gilberts syndrome

- feto protein
Resembles albumin genetically &
functionally
Formation
sitesyolksac,
hepatocytes, enterocytes
Fetal & neonatal life- major
determinant of plasma oncotic
pressure
1 year of age- albumin largely
replaces AFP

//

There is no ideal study to evaluate the livers


diverse functions.
Abnormal liver biochemistries are often the first
indication of liver disease.
The widespread inclusion of these tests in routine
blood chemistry panels uncovers many patients with
unsuspected hepatic dysfunction.
Laboratory testing may provide information about
the severity of liver disease and its prognosis

//

//

Hepatobiliary imaging
USG, CT scan - 1st line
investigation
ERCP visualization
biliary tract

of

Doppler & MRI hepatic


vasculature & heamodynamics
CT & MRI- hepatic masses
& tumours

//

Biopsy
Despite advances in serological testing
and imaging, liver biopsy remains the
golden standerd to confirm the
diagnosis of specific liver diseases such
as
Wilson disease
Nonalcoholic steatohepatitis
Assess prognosis in many forms of
parenchymal liver disease such as
chronic viral hepatitis
Evaluate allograft dysfunction in liver
transplant recipients.

Indications for liver biopsy


Evaluation of abnormal liver biochemical tests and hepatomegaly
Evaluation and staging of chronic hepatitis
Identification and staging of alcoholic liver disease
Recognition of systemic inflammatory or granulomatous disorders
Evaluation of fever of unknown origin
Evaluation of the type and extent of drug-induced liver injury
Identification and determination of the nature of intrahepatic masses
Diagnosis of multisystem infiltrative disorders
Evaluation and staging of cholestatic liver disease (primary biliary
cirrhosis, primary sclerosing cholangitis)
Screening of relatives of patients with familial diseases
Obtaining of tissue to culture infectious agents (e.g., mycobacteria)
Evaluation of effectiveness of therapies for liver diseases (e.g., Wilson
disease, hemochromatosis, autoimmune hepatitis, chronic viral
hepatitis)
Evaluation of liver test abnormalities following transplantation

//

Contraindications to liver biopsy

Complications
Post-biopsy pain with or without radiation to the right shoulder
occurs in up to one-third of patients.
Intraperitoneal bleeding is the most serious complication.
Increasing age, presence of hepatic malignancy, and the number
of passes made are predictors of the likelihood of bleeding, as is
the use of a cutting rather than a suction needle
Pneumothorax may require a chest tube, whereas serious
bleeding may be controlled by selective embolization at
angiography or, if necessary, ligation of the right hepatic artery
or hepatic resection
Biopsy of a malignant neoplasm carries a 13% risk of seeding
of the biopsy track with tumor

//

Liver Test

Abnormal in...

Albumin

Cirrhosis, severe hepatocellular injury

Alkaline phosphatase

Cholestasis, hepatocellular enzyme induction, canalicular injury, children


during bone growth, bone disease, pregnancy (placenta origin)

Aminotransferases
(AST, ALT)

Hepatocellular injury (ethanol, drug-induced hepatitis, hepatitis B and C,


ischemic injury, chronic liver disease, NAFLD, chronic viral hepatitis,
alcoholism, nonspecific viral injury, and cholestatic or replacement disease);
acute biliary obstruction; rarely in hyperthyroidism, celiac disease, skeletal
muscle disease

Bilirubin

Any acute or chronic liver disease; congenital disorders of bilirubin


metabolism.

5 nucleotidase

Cholestasis

GGT

Cholestasis; medications, ethanol; rarely anorexia nervosa, hyperthyroidism,


myotonic dystrophy

INR

Impaired synthesis of vitamin K-dependent coagulation factors

Lactate dehydrogenase Ischemic injury, Epstein-Barr virus infection, hemolysis, solid tumor

Uric acid

Alcohol consumption, gout