The liver - liver.pdftests that are indicators of liver injury or biliary tract disease. ......
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Dr. Mohammad Saadeh
The requirements for the Clinical Chemistry
Faculty of pharmacy
The liver is the largest organ in the body.
The liver is of vital importance in intermediary metabolism and in the
detoxification and elimination of toxic substance.
Structure of liver:
1. 60% hepatocytes
2.30% kupffer cell (reticuloendothelial )
3.10% Supporting tissue
The liver performs an astonishingly
large number of tasks that impact all
Liver have two channels that can
supply and oxygen nutriment :
hepatic artery and hepatic portal
The corresponding channels is
hepatic vein and bile ducts.
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
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. Liver is responsible for the metabolism of xenobiotic.
Liver function tests (LFTs)
Liver function tests (LFTs or LFs) are groups of blood tests that give
information about the state of a patient's liver and can contribute to making an
accurate diagnosis of the specific liver disorder.
LFTs are divided into:
true tests of liver function,
such as serum albumin, bilirubin, and Prothrombin time.
tests that are indicators of liver injury or biliary tract disease.
Typically the LFT comprises of:
1. Total protein.
2. Albumin and globulin.
3. (Prothrombin Time).
4. Transaminases such as AST & ALT.
5. Alkaline phosphatase.
7. Gamma Glutamyl Transpeptidase (GGT).
Liver function tests
Most common live disease:
Hepatitis: acute or chronic damage to and destruction of
Cirrhosis: fibrosis, shrinkage liver, decrease number and
function of hepatocellular.
Jaundice: high plasma concentration of bilirubin.
Cholestasis is defined as a decrease in bile flow due to
impaired secretion by hepatocytes or to obstruction of bile
flow through intra-or extrahepatic bile ducts.
Note: Obstruction bile duct may cause jaundice or cirrhosis.
Liver function tests
These biochemical investigation can assist in differentiating the
Obstruction to the biliary tract.
Acute hepatocellular damage.
Chronic liver disease.
Classification of liver functions test
Classified based on the major functions of liver:
Excretion: Measurement of bile pigments, bile salts.
Serum enzymes: Transaminase (ALT, AST), alkaline phosphate (ALP),
5-nucleotidase, LDH isoenzyme.
Synthetic function: Prothrombin time, serum albumin.
Metabolic capacity: Galactose tolerance and antipyrine clearance
Detoxification : urea.
1. 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
Effective bilirubin conjugation and excretion depend on
hepatobiliary function and on the rate of RBC turnover.
1. Serum bilirubin:
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.
Bilirubin metabolism serum bilirubin levels are reported as
1. Total bilirubin (conjugated and unconjugated) (normal value
= 0.3-1.2 mg/dl).
2. Direct bilirubin (conjugated bilirubin) (normal value 0.4
mg/dl), filtrated by glomerulurs.
Bilirubin is released by Hb breakdown and is bound to
albumin as water-insoluble indirect bilirubin (unconjugated
bilirubin), which is not filtrated by glomerulurs.
Unconjugated bilirubin travels to the liver, where it is
separated from albumin, conjugated with monoglucuronide
(25%) and diglucuronide (75%) (more water soluble), and
then actively secreted into bile as conjugated bilirubin (direct
bilirubin), which is filtrated by Glomerulurs.
Figure in the next slide
Binding with Glucuronic acid no yes
Reacting with the diazo reagent
Slow and indirect
Rapid and direct
solubility in water small large
Discharged via kidney no yes
Pass through the
membrane of cell yes no
Difference of two bilirubins
A. 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/24 hours.
Urobilin is the final product of oxidation of urobilinogen by oxygen in
air. The amount change with the amount of urobilinogen excretion .
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 avid
binding to albumin. (bilirubin-albumin complex is too large)
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.
There are three major causes of increased serum bilirubin
1. Hemolytic Jaundice, increases total bilirubin; direct bilirubin
(conjugated) is usually normal. Urine color is normal, and no
bilirubin found in urine.
2. Hepatic Jaundice, occur in viral hepatitis; may cause an
increase in both direct and indirect bilirubin. Urine color is dark,
and bilirubin is present in the urine.
3. Obstructive jaundice ( Cholestasis), may be intrahepatic or
extrahepatic, increase direct and indirect bilirubin. Urine color is
dark, and bilirubin is present in the urine.
Who is a candidate for the test? Bilirubin is used to diagnosis of jaundice.
Abnormal bilirubin levels can be found in many disorders, including:
blocked bile ducts
immature liver development in newborns.
Liver function tests
2. Serum enzymes
Increase (total bilirubin and ALP) OR (ALP and GGT) are indices of
cholestasis (blockage of bile flow). vvi
Increase ALT and AST measure the integrity of liver cells. vvi
Albumin and Prothrombin time measure the liver synthetic capacity.
Standard group of test Property being assessed
Serum albumin, PT Protein synthesis
Serum bilirubin (total) Hepatic anion transport
Serum enzyme activity
ALT, AST Hepatocellular integrity
ALT, GGT Presence of cholestasis
Liver function tests
2. Serum enzymes
Alkaline phosphatase (ALP or GPT) (remember)
diagnosis of two groups of conditions; increase in hepatobiliary disease
(obstructive jaundice, cirrhosis, hepatitis and metastic) and bone disease
associated with increased osteoblastic activity (child's rickets with D vitamin
deficiency, Paget's disease, hyperparathyroidism with skeletal).
extraheptic biliary obstruction; example
Stone in bile duct.
ALP Physiologically increase in; Pregnancy, Childhood, Fatty meals.
Liver function tests; 2. Serum enzymes -Glutamyl transferase (GGT): levels are elevated in:(remember)
liver diseases such as alcoholic cirrhosis and drug such as phenytoin.
5' nucleotidase (5'NTD):(hydrolysis of a nucleotide into a nucleoside and a phosphate)
5' Nucleotidase (5'NTD) is another test specific for cholestasis or damage to
the intra- or extrahepatic biliary system
Elevated ALP and GGT or 5'NTD suggest that the liver is the source.
1. AST (GOT) increased in
Acute hepatitis (cell damage) Hepatobiliary diseases such as cirrhosis.
2. ALT (GPT) levels are el