Alcoholic liver disease
3.
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Secondary metastasis to liver
4.
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Undiagnosed chronic illness5.
Coagulation disorder
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6.
Before administration of certain drugs
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7.Annual check up of diabetes mellitus
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In liver diseases-To detect presence of liver disease
Distinguish among different types of liver
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disordersGauge the extent of known liver disease
Follow the response to treatment
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Some tests are associated with
FUNCTIONALITY (e.g. PT/INR, Albumin,
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Bilirubin),some with CELLULAR INTEGRITY (e.g.
transaminases) and
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some with conditions linked to BILIARY
TRACT (GGT and ALP)
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.....and hence liver biochemical tests areclassified into following groups:
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BIOCHEMICAL CLASSIFICATION1. TESTS BASED ON LIVER EXCRETORY FUNCTION
a)
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Serum bilirubin- total
- conjugated
- unconjugated
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b) Urine ? bile pigment- bile salt
- urobilinogen
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2. Liver enzymesI.
AST
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II.ALT
III. ALP
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IV. GGT
3. TESTS BASED ON LIVER SYNTHETIC FUNCTION
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I.
SERUM TOTAL PROTEIN
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II.SERUM ALBUMIN
III. ALBUMIN GLOBULIN RATIO
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IV. PROTHROMBIN TIME
4.
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SPECIAL TESTS (TESTS DONE IN SPECIAL
SITUATIONS ) ARE:
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i) Ceruloplasmin
ii) Transferrin
iii) -1Anti Trypsin
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iv ) Alpha Feto ProteinCLINICAL CLASSIFICATION
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...Group I: Markers of liver dysfunction
Serum bilirubin: total = conjugated+
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UnconjugatedUrine: urobilinogen, bile salts and bilirubin
Total protein, serum albumin, globulin and
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albumin/globulin ratioProthrombin Time
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Group II: Markers of hepatocellular injuryAlanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
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Group III: Markers of cholestasis
Alkaline phosphatase (ALP)
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g-glutamyltransferase (GGT)
Group IV :Special tests (tests done in special
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situations ) are
Ceruloplasmin
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procollagen IIITransferrin
peptide
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-1Anti Trypsin
Bromsulphthalein
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testAlpha Feto Protein
Anti-mitochondrial
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Blood ammonia
antibody test
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Galactosetolerance test
Biochemical test
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for liver fibrosis
Normally, a small amount of bilirubin
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circulates in the blood.
Serum bilirubin is considered a true test of
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liver function, as it reflects the liver's abilityto take up, process, and secrete bilirubin
into the bile
A. Indirect bilirubin (normal value = 0.3 - 1.2
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mg/dl)
B. Direct bilirubin (normal value 0.4 mg/dl)
C.Total bilirubin (normal value =0.3-1.2 mg/dl)
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If the plasma bilirubin level exceeds 1.2mg/dl,
the condition is called hyperbilirubinemia.
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Levels between 1.2 & 2.5 mg/dl are indicative
of latent jaundice.
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When the bilirubin level exceeds 2.5 mg/dl, itdiffuses into tissues producing yellowish
discoloration of sclera, conjunctiva, skin &
mucous membrane resulting in jaundice.
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latent jaundice 1.2-2.5 mg/dl
Clinical jaundice > 2.5 mg/dl
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Icterus is the Greek term for jaundice.It's level confirms jaundice, and used to assess
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the prognosis.
It's level represents the balance between input
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from production and hepatic removal of thepigment.
Unconjugated hyperbilirubinemia is due to
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overproductionor
impaired
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uptake
or
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conjugation of bilirubin.Conjugated
hyperbilirubinemia is due to
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decreased excretion or backward leakage of the
pigment.
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Normal serum gives a negative van den berghreaction.
PRINCIPLE OF THE REACTION:
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The reagent is a mixture of equal volumesof sulfanilic acid in dilute HCl and sodium
nitrite. (DIAZOTISED SULFANILIC ACID )
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That diazotised sulfanilic acid reacts withbilirubin to form a purple coloured
AZOBILIRUBIN.
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Direct Positive: conjugated bilirubin gives a
purple color immediately on addition of the
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reagent.Indirect Positive: Purple color develops only
when the reagent and methanol are added.
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Unconjugated bilirubin gives color only when
methanol is added.
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BiPhasic: Purple color develops on addition ofreagent. Addition of methanol intensifies the
color.
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Elevation of both unconjugated and
conjugated bilirubin
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Indirect Positive----- Hemolytic jaundice
Direct Positive ----- Obstructive jaundice
Biphasic ----- Hepatic jaundice
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Depending upon the etiology of hepatitis :
Conjugated hyperbilirubinemia:-
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Viral hepatitis
Alcoholic hepatitis
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Toxic hepatitisActive cirrhosis
Genetic disease? Dubin johnson syndrome and
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rotor's syndrome
Unconjugated hyperbilirubinemia:-
crigler najjar and gilbert's syndrome
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physiological jaundice of newborn
ENTERO HEPATIC CIRCULATION
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2.URINE UROBILINOGEN
UBG is formed in terminal ileum and colon from
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conjugated Bb by Clostridium ramosum, helped by
E.coli.
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UBG excreted in stool is called stercobilinogen. It isconverted by colonic bacteria to stercobilin which
imparts the normal brown colour of stools.
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Hence in cholestatic jaundice stools are pale as Bb
can not reach the gut and hence stercobilin is not
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formed.About 20% of UBG is reabsorbed and undergoes
enterohepatic circulation.
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Increase in UBG in urine is found in hepatitis as
damaged hepatocytes are not able to reexcrete the
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UBG absorbed from gut. It is thus a good index ofhepatocellular dysfunction, often when other tests
are normal.
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Urine UBG is increased in :
1)hepatitis 2)malignant disease of liver
3)cirrhosis 4)hemolytic anaemia
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UBG is absent in :
1) complete biliary obstruction
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2) severe bilirubin glucoronyl transferasedeficiency as seen in CN syndrome type I.
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3.URINE BILE SALTBile salts are formed in the liver from cholesterol
They are excreted in bile
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Facilitate absorption of fat from intestine
Constitute a substantial amount of bile in bilirubin
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excretion and can be used in diagnosing cholestasisPrimary bile salts ? cholate and chenodeoxycholate are
produced in liver
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Metabolised by bacteria in intestine
Produces secondary bile salts ? lithocholate,
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deoxycholate and ursodeoxycholateIn cirrhosis ? reduced ratio of primary to secondary bile
salts
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In cholestasis ? as secondary bile salts are not formed ?
so increased ratio of primary to secondary bile salts.
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In normal condition ? renal excretion of bile
salts is negligible
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In Hepatocellular jaundice, swollen liver cellscompress biliary canaliculi
Hence, there is intrahepatic obstruction of
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biliary canaliculi
Bile salts cannot reach intestine, they are
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regurgitated from liver into systemiccirculation and appear in urine
4.URINE BILIRUBIN
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Bilirubin is not normally present in urine and
faeces since bacteria in intestine reduce it to
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urobilinogen.The kidneys do not filter unconjugated bilirubin
because of its avid binding to albumin.
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Conjugated bilirubin can pass through glomerular
filter.
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Conjugated bilirubin in serum is raised inhepatocellular and obstructive jaundice.
Therefore, bilirubin is present in urine in
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hepatocellular and obstructive jaundice
Bilirubin in the urine may be detected even
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before clinical jaundice is noted.Recovering from jaundice urine bilirubin clears
prior to Sr bilirubin
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5.DETERMINATION OF TOTAL PROTEIN ,ALBUMIN,
GLOBULIN & A:G RATIO
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This yields most useful information in chronic
liver diseases.
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Liver is the sole site for synthesis of most plasmaproteins except immunoglobulin (gamma
globulins)
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Normal value:
total serum proteins =6.0 to 8.0 gm/dl,
serum albumin (A) = 3.5 to 5.0 gm/dl.
serum globulin(G)= 2.5-3.5 gm/dl
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A:G RATIO=1.5:1 to 2.5:1Serum albumin comprises 60% of all plasma
proteins
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Half-life of albumin is 14 to 21 days makes itunreliable in acute liver failure
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In infectious hepatitis:quantitative estimations of albumin and
globulin may give normal results in the early
stages. qualitative changes may be present,
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in early stage rise in -globulins and in laterstages -globulins shows rise.
cirrhosis or parenchymal liver disease:
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The albumin is grossly decreased and theglobulins are often increased, so that A:G
ratio is reversed, is characteristically seen in
cirrhosis of liver.
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6.PROTHROMBIN TIME
With the exception of F-VIII , all other
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coagulation factors are synthesized in liverHalf life ranges from 6hrs for F-VII to 5 days for
fibrinogen
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So their measurement is the single best measure
of hepatic synthetic function
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Measured by Prothrombin timeProthrombin vitamin K thrombin
?Marked increase in PT >5secs above the control
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and not corrected by Vit K administration ? is a
poor prognostic sign in acute viral hepatitis and
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other acute and chronic liver diseaseALANINE TRANSAMINASE (ALT)
7.SERUM TRANSAMINASE
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ASPARTATE TRANSAMINASE (AST)Liver enzymes are important markers of
hepatocellular damage & severity of liver
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diseases.
AST
Heart, skeletal muscle, brain, pancreas, lung, RBC
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and kidney.
20% cytosolic and 80 % mitochondrial
serum half life of 17 hrs.
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ALTALT is more specific for liver
Low concentrations in kidney and skeletal muscles
serum half life of 47 hrs
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DE RITI'S RATIO: THE AST:ALT RATIO
Normal ratio is 0.7 to 1.4.
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In alcoholic hepatitis, the AST:ALT ratio isalways 2:1.
The ratio is usually <1 in patients with acute
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and chronic non- alcoholic hepatitis.
q Most marked elevations of ALT and AST (>15
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times normal) are seen in? acute viral hepatitis
? toxin-induced hepatocellular damage (e.g.
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carbon tetrachloride and? centrilobular necrosis due to ischemia
(congestive cardiac failure).
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Moderate elevations (5-15 times) occur in
Chronic hepatitis,
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autoimmune hepatitis
alcoholic hepatitis
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acute biliary tract obstructiondrug-induced hepatitis
q Mild elevations (1-3 times) are seen in
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cirrhosis,
nonalcoholic steatosis
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cholestasis.Diagnostic value of transaminases
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The first laboratory abnormality detected inearly phase of viral hepatitis is elevated
transaminases
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In anicteric hepatitis and inapparent hepatitisthe only biochemical abnormality may be an
elevated ALT or AST.
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Fluctuating levels of transaminases may be seenin hepatitis C infection .
In hepatitis, elevation of transaminases
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precedes that of bilirubin by about one week.
During recovery phase of viral hepatitis, there
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is a steady fall in level of transaminases.8. Alkaline phosphatase
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Alkaline phosphatase (ALP) is synthesized inliver, bones, intestine and placenta
In liver, ALP is synthesized by parenchymal cells
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as well as epithelial cells of biliary canaliculi
Serum ALP is mildly raised in viral hepatitis due
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to necrosis of parenchymal cellsA marked elevation in serum ALP occurs in
obstructive jaundice
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The rise is due to increased synthesis of ALP
caused by irritation of epithelial cells of biliary
canaliculi
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9.GAMMA GLUTAMYL TRANSPEPTIDASE ( GGT)
It is synthesized by epithelium of small bile
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ductules and hepatocytes
GGT levels are higher in biliary tract disease
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and cholestasis than in hepatocellular disease.Rise in serum GGT is a sensitive indicator of
alcoholic hepatitis
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An elevated GGT is used to confirm that a
raised ALP is of hepatobiliary origin. Hence it
is a more sensitive marker compared to ALP.
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10.SPECIAL TESTS
A.Ceruloplasmin
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Normal plasma levels - 0.2-0.4g/L? Acute phase protein
Decreased in multiple conditions
1. Wilson's disease (Hepatolenticular
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degeneration)2. Menkes disease
3. Aceruloplasminemia
4. Copper deficiency
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B.Blood ammonia
In advanced liver disease, liver may fail to
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convert ammonia into urea
Increased blood ammonia
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can cause hepatic encephalopathyMeasurement of blood ammonia helps in its
diagnosis and monitoring.
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C.ALPHA -1 ANTITRYPSIN (-1 AT)
Major -1 globulin protein
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Responsible for 90% of plasma trypticinhibitory capacity
-1 AT deficiency is a major cause of chronic
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liver disease in children
Less commonly, of chronic liver disease
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presenting in adulthood.D.TRANSFERRIN
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An iron transfer protein ( Normal-30-40%saturated)
Its saturation is used as a screening test for
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Hemochromatosis ( >60% saturated)
Decreased saturation is found in cirrhosis and
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malnutrition.E. ALPHA FETO PROTEIN
Normal component of fetal blood but
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disappears few week after birth.Mild elevation is seen in cirrhosis, acute and
chronic hepatitis
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Higher concentration is seen in hepatocellular
carcinoma.
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F. GALACTOSE TOLERANCE TEST
Galactose is almost exclusively metabolized by
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the liver.The liver function can be assessed by measuring
the utilization of galactose.
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The subject is given intravenous administration
of galactose (about 300 mg/kg body weight).
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Blood is drawn at 10 minute intervals for thenext 2 hours & galactose estimated.
In the normal individuals, the half-life of
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galactose is about 10-15 minutes.
This is markedly elevated in hepatocellular
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damage (infective hepatitis, cirrhosis).G. BROMOSULPHTHALEIN DYE TEST
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Bromosulphthalein is a dye used to assess theexcretory function of liver.
It is a non-toxic compound & almost exclusively
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excreted by the liver (through bile).
BSP is administered intravenously (5 mg/kg body
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weight) & its serum concentration is measured at45 min & at 2 hrs.
In normal individuals, <5% of the dye is retained at
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the end of 45 min.Any impairment in liver function causes an
increased retention of the dye.
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Increased plasma retention can result from
decreased excretory rate as seen in Dubin Johnson
Syndrome.
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H. Mitochondrial Antibodies Test
The presence of these antibodies can
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indicate
? primary biliary cirrhosis,
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? chronic active hepatitis, and? certain other autoimmune disorders.
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11.TEST TO DETECT HEPATIC FIBROSISliver biopsy is the standard for the assessment of
hepatic fibrosis.
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Need has arrived to go for non invasive tests.
Single
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serum biochemical markers thatpotentially reflect the activity level of hepatic
fibrogenesis - Hyaluronan.
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A fasting hyaluronan level greater than 100 mg/L(sensitivity83% & specificity78%)for the detection
of cirrhosis in patients with a variety of chronic
liver diseases like chronic hepatitis C, chronic
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hepatitis B, alcoholic liver disease, andnonalcoholic steatohepatitis
ASCITES FLUID
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THE SPECIAL "LFT"
PARACENTESIS
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Tests
4 C's: Cells, Culture, Chemistry, Cytology
Cell count and differential, gram stain, culture,
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albumin, total protein, glucose, LDH, cytology
Optional: amylase, bilirubin, Cr, TG, AFB cx +
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adenosine deaminaseCalculation of SAAG
SAAG = [Serum albumin] ? [Ascites albumin]
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What does the SAAG indicate?
If 1.1 g/dL, portal HTN is very likely (~97%
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accurate1)If < 1.1 g/dL, portal HTN is unlikely.