Liver function tests
xiaoli
( LFTs )
Review: LiverReview: Liver
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 an astonishingly large number 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.
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 liverFunctions of liver① Excretory function: bile pigments, bile salts and
cholesterol are excreted in bile into intestine.
② Metabolic function: liver actively participates in carbohydrate, lipid, protein, mineral and vitamin metabolisms.
③ 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.
④ Storage functions: glycogen, vitamins A, D and
B12,and trace element iron are stored in liver.
⑤ 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 )
What is Purpose of LFTs?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. Different tests will show abnormalities in response to liver inflammation liver injury due to drugs, alcohol, toxins, viruses Liver malfunction due to blockage of the flow of bile Liver cancers
LFTs are divided into
true tests of liver function,
such as serum albumin, bilirubin, and
protime, tests that are indicators of liver injury or
biliary tract disease.
Classification of liver functions testClassification of liver functions test
Classified based on the major functions of liver:
① Excretion: Measurement of bile pigments, bile salts.
② Serum enzymes: Transaminase (ALT, AST), alkaline
phosphate(ALP), 5’-nucleotidase, LDH isoenzyme.
③ Synthetic function: Prothrombin time, serum albumin.
④ Metabolic capacity: Galactose tolerance and antipyrine
clearance
⑤ Detoxification :
1. Excretion1. Excretion : Bilirubin : 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.
via bile duct to intestines
Stercobilin excreted in feces
Urobilinogen formed by bacteria
KIDNEY
Urobilin excreted in urine
BLOOD CELLS
CO
Biliverdin IX
Heme oxygenase
O2
Bilirubin (water-insoluble)
NADP+
NADPH
Biliverdinreductase
HemeGlobin
Hemoglobin
reabsorbed into blood
LIVER
Bilirubin diglucuronide(water-soluble)
2 UDP-glucuronic acid
Bilirubin (water-insoluble)via blood
to the liver
INTESTINE
Fig. 2 metabolism of bilirubin
A. indirect bilirubin (normal value = 0.3 - 1.2 mg/dl)
1. serum bilirubin:
B. direct bilirubin (normal value ≤ 0.4 mg/dl)
C. total bilirubin Normal value for = 0.3- 1.2 mg/dl.
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.
♣ Direct Bilirubin + Diazotized Sulfanilic Acid → Azobilirubin (Redish purple)
♣ total bilirubin + dimethylsulfoxide(DMSO)+methanol
+diazotized sulfanilic acid to form azobilirubin.
Indirect bilirubin react with diazotized sulfanilic acid after
addition of methanol.
The absorbance of the reaction mixture at 555 nm is directly proportional to the concentration of direct bilirubin.
VD Bergh reaction
目 录
H H H
CH2
CH2
CO
NCHO
NCH2 N
H
CHN
O
M M M MV VCH2
CH2
CO
O OOH
HO
COOH
OH
O
OH
OHHOOC
OH
O
indirect bilirubin
direct bilirubin
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)
2. urine(/faeces)
Normally there are mere traces of urobilinogen in the
urine. average is 0.64mg , maximum normal 4mg/24hours.
B. Urobilin Urobilin is the final product of oxidation of urobilinogen by
oxygen in air. The amount change with the amount of
urobilinogen excretion .
B. bilirubinurine:
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.
conjugated bilirubin can pass through glomerular filter.
Bilirubin is found in the urine in obstructive jaundice due to various causes and in cholestasis.
Note:
Bilirubin in the urine may be detected even before clinical jaundice is noted.
Who is a candidate for the test?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, cirrhosis,
hepatitis and other liver diseases or immature liver
development in newborns.
Hemolytic Jaundice
Hepatic Jaundice
Obstructive jaundice ( Cholestasis)
Congenital Jaundice
Sample Indices Normal Hemolytic Jaundice
Hepatic Jaundice
Obstructive Jaundice
Serum Total Bil < 1mg/dl > 1mg/dl > 1mg/dl > 1mg/dl
Direct Bil 0 ~ 0.8mg/dl
↑ ↑↑
Indirect Bil < 1mg/dl ↑↑
Urine Color normal deeper deep deep
Bilirubin — — ++ ++
Urobilinogen A little ↑ uncertain ↓
Urobilin A little ↑ uncertain ↓
Stool Color normal deeper lighter or normal
Argilous (complete
obstruction)
2. Serum enzymes2. Serum enzymes
A large number of enzyme estimations are available which are used to ascertain liver function. They are be divided into two groups:
I: most commonly and routinely done in the laboratory.
serum transaminase(ALT/AST)
serum alkaline phosphate(ALP)
II: not routinely done in the laboratory.
Alanine transaminaseAlanine transaminase (ALT) (ALT)
ALT or sGPT (serum glutamate pyruvate transaminase)
GPTGPT
Aspartate aminotransferaseAspartate aminotransferase (AST) (AST)
AST or sGOT (serum glutamate oxaloacetate
transaminase)
GOT
organ GOT GPT
heart 156000 7100
liver 142000 44000
skeletal 99000 4800
kidney 91000 19000
organ GOT GPT
pancrease
spleen
lung
serum
28000 2000
14000 1200
10000 700
20 16
GPT:
Normal range: 2-59 U/L
GOT:
Normal range: 10-34 U/L
Elevated levels of GPT may indicate : 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
‼ Therefore, when the liver is injured, GPT is
released into the bloodstream.
GOT 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 (heart
attack).
Elevated levels of GOT may indicate : 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
◆ normally: GPT is normal, GOT is normal, GPT/GOT is
about 1.15.
◆ Virus hepatitis: GPT↑, GOT is normal ,GPT/GOT >1,even more than 2.5;◆ chronic hepatitis : GPT↑ ,GOT ↑GPT/GOT is about 1.
◆ Liver cancer, cirrhosis, Alcohol-induced hepatitis:
GPT↑ ,GOT ↑ < 1, about 0.6~0.7.
◆ Accute myocardial infarct :< 1
Although GOT is not a specific for liver as the GPT,
ratios between GPT and GOT are useful to physicians in
assessing the etiology of liver enzyme abnormalities.
GPT and GOT is in the different distribution of the hepatocytes. GPT exists primarily in the cytoplasm of liver cell. if there is a slight liver cell damage, GPT firstly leak into the bloodstream, so that the serum GPT increased.
The GOT mainly in the "mitochondria“of liver cells, the mitochondria are "bubble" in the liver cell cytoplasm. if there is a slight liver cell damage, GOT don`t leak into the bloodstream.
When the GOT was significantly higher, mitochondria of liver cells are injuries.
Alkaline phosphatase (ALP) (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)
Alkaline phosphatase (ALP or AKP)Alkaline phosphatase (ALP or AKP)
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, alkaline phosphatase is present in all tissues throughout the
entire body, but is particularly concentrated in liver, bile duct, kidney, bone, and the placenta.
Levels are significantly higher in children and pregnant women.
Higher levels of ALP than normal may indicate: liver disease bone disease leukemia, a cancer of the blood and bone marrow various hormone problems pregnancy
Lower levels of ALP than normal may indicate: anemia, or a low red blood cell count malnutrition various hormone problems
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.
It is used for many years in differential diagnosis of jaundice. it is increased in both infectious hepatitis (viral hepatitis) and posthepatic jaundice, but the rise is usually much greater in case of obstructive jaundice .
dividing line which has been suggested is 35KA units/ml. a value higher than 35KA units/ml is strongly suggestive of diagnosis of obstructive jaundice, in which very high figures even up to 200KA units/ml or more may be found.
Serum ALP is found to be normal in haemolytic jaundice.
5’-Nucleotidase5’-Nucleotidase
This enzyme is released by the liver when
the liver is injured due to bile duct obstruction or
impaired bile flow.
Normal range: 2-15 IU/L
Other enzyme (not done routinely)
LDH isoenzymesLDH isoenzymes
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.
lactate dehydrogenaselactate dehydrogenase
HH HH
HH HH
HH HH
HH MM
HH HH
MMMM
HH
MMMM
MM
MMMM
MMMM
LDHLDH11
(H(H44))LDHLDH22
(H(H33MM))
LDHLDH33
(H(H22MM22))
LDHLDH44
(HM(HM33))
LDHLDH55
(M(M44))
LDH isoenzymesLDH isoenzymes۩ Tissue or organ injury can release LDH into the bloodstream, thereby raising the level. So it is usually done to see if tissue or organ damage has occurred.
۩ If he or she suspects a heart attack or liver tissue damage in the body. Normal range: 115-225 IU/L
3. Metabolic capacity3. Metabolic capacity::
Tests based on livers function:
carbohydrate metabolism
lipid metabolism
protein metabolism
Tests based on livers part in carbohydrate metabolism
1. Glucose tolerance test
& 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.
2. Galactose tolerance test
Basis: For galactose is a monosaccharide, almost exclusively metabolized by the liver. the normal liver is able to convert galactose into glucose; but 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. This is referred to galactose tolerance test.
◆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.
The test is performed in the morning after a night’s
fast. a fasting blood sample is collected which serves as
“control”.40mg galactose dissolved in a cup-full of water
is given orally.further blood samples are collected at ½
hourly intervals for two hours.
oral galactose tolerance testoral galactose tolerance test
Method :
oral galactose tolerance test
IV galactose tolerance test(intravenous injection )
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.
Result:
Intrahepatic jaundice:
The excretion amounts to 4 to 5gm or more during the first 5 hours.
3. Fructose tolerance testNormal 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%.
obstructive jaundice cases: mresult is obtained in most cases of obstructive jaundice cases.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 livers part in 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: theer 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, whilst there is marked reduction in the %
present as esters.
Tests based on livers part in 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 .
Normal range :
blood ammonia varies from 40μg ammonia nitrogen
per100ml of blood.
In parenchymatous liver disease: Increases in NH3 can be found more advanced cases of
cirrhosis liver,particular when there areassociated neurological
complicate.in such cases blood levels may be over 200 μ g/ml.
4. Synthetic functions:4. Synthetic functions:
1. total plasma proteins/ albumin/ globulin/ A:G ratio
2. Formation of prothrombin by liver
1. Determination of total plasma proteins/ albumin/ globulin/ A:G ratio
Normal value: total plasma proteins: 80~110mg/dl
albumin:40-50mg/dl
globulin:25~35mg/dl
A:G ratio: 1.5~2.5
This yields most useful information in chronic liver disease.Liver is the site of albumin synthesis and also possibly of some of α and β globulins.
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 β -globulins and in later stages γ-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.
Serum AlbuminSerum Albumin
★ 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.
Ascites :Ascites : the abnormal the abnormal
accumulation of fluid within the accumulation of fluid within the
abdominal and pelvic cavityabdominal and pelvic cavity
(A)Patient with alcoholic cirrhosis who
shows ascites, an umbilical hernia,
and wasting of muscle.
(B) After 2 years of abstinence and
appropriate nutrition, the patient
gained back muscle mass and his
ascites improved.
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.
Normal range: 34 - 54 g/L
Abnormally low contents of albumin may indicate: ascites extensive burns kidney disease liver disease malabsorption syndromes
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)PT (Prothrombin time)
Estimation of plasma fibrinogenEstimation of plasma fibrinogen
APTT(activated partial thromboplastin time)APTT(activated partial thromboplastin time)
Formation of prothrombin by liver
Prothrombin time (protime or PT)Prothrombin time (protime or PT)
★ 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.
thrombin prothrombin
in presence of vitamin K
Ca2+, PL
★ 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 patient’s blood.
What is prothrombin time?
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.
This test may be done: when a person has a bleeding problem to monitor a person who is taking blood-thinning medicine before surgery to make sure a person will not bleed too
much during the operation.
It generally falls 10 - 15 seconds. Prothrombin activity is also sometimes expressed as
“prothrombin index”, which is the ratio of prothrombin time
of the normal control to the patient’sprothrombin time:
prothrombin index = PT of normal control
PT OF patientx100
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-disseminated intravascular clotting, 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 birth
control pills
Some other tests for LFTsSome other tests for LFTs Alpha-fetoprotein Test: This protein is produced by the fetal
liver and testes indicating hepatitis or cancer.
Mitochondrial Antibodies Test: The presence of these
antibodies can indicate primary biliary cirrhosis, chronic active
hepatitis, and certain other autoimmune disorders. Platelet count: Platelets are the smallest of all blood cells and
are involved in promoting clotting of the blood, normally a
process of healing. 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.
Total protein: measures albumin and all other proteins in
blood, including antibodies made to help fight off infections
Protective functions and detoxification: