Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest LFT Lecture PPT
1.
Jaundice
2.
Alcoholic liver disease
3.
Secondary metastasis to liver
4.
Undiagnosed chronic illness
5.
Coagulation disorder
6.
Before administration of certain drugs
7.
Annual check up of diabetes mellitus
In liver diseases-
To detect presence of liver disease
Distinguish among different types of liver
disorders
Gauge the extent of known liver disease
Follow the response to treatment
Some tests are associated with
FUNCTIONALITY (e.g. PT/INR, Albumin,
Bilirubin),
some with CELLULAR INTEGRITY (e.g.
transaminases) and
some with conditions linked to BILIARY
TRACT (GGT and ALP)
.....and hence liver biochemical tests are
classified into following groups:
BIOCHEMICAL CLASSIFICATION
1. TESTS BASED ON LIVER EXCRETORY FUNCTION
a)
Serum bilirubin- total
- conjugated
- unconjugated
b) Urine ? bile pigment
- bile salt
- urobilinogen
2. Liver enzymes
I.
AST
II.
ALT
III. ALP
IV. GGT
3. TESTS BASED ON LIVER SYNTHETIC FUNCTION
I.
SERUM TOTAL PROTEIN
II.
SERUM ALBUMIN
III. ALBUMIN GLOBULIN RATIO
IV. PROTHROMBIN TIME
4.
SPECIAL TESTS (TESTS DONE IN SPECIAL
SITUATIONS ) ARE:
i) Ceruloplasmin
ii) Transferrin
iii) -1Anti Trypsin
iv ) Alpha Feto Protein
CLINICAL CLASSIFICATION
...
Group I: Markers of liver dysfunction
Serum bilirubin: total = conjugated+
Unconjugated
Urine: urobilinogen, bile salts and bilirubin
Total protein, serum albumin, globulin and
albumin/globulin ratio
Prothrombin Time
Group II: Markers of hepatocellular injury
Alanine aminotransferase (ALT)
Aspartate aminotransferase (AST)
Group III: Markers of cholestasis
Alkaline phosphatase (ALP)
g-glutamyltransferase (GGT)
Group IV :Special tests (tests done in special
situations ) are
Ceruloplasmin
procollagen III
Transferrin
peptide
-1Anti Trypsin
Bromsulphthalein
test
Alpha Feto Protein
Anti-mitochondrial
Blood ammonia
antibody test
Galactose
tolerance test
Biochemical test
for liver fibrosis
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 =0.3-1.2 mg/dl)
If the plasma bilirubin level exceeds 1.2mg/dl,
the condition is called hyperbilirubinemia.
Levels between 1.2 & 2.5 mg/dl are indicative
of latent jaundice.
When the bilirubin level exceeds 2.5 mg/dl, it
diffuses into tissues producing yellowish
discoloration of sclera, conjunctiva, skin &
mucous membrane resulting in jaundice.
latent jaundice 1.2-2.5 mg/dl
Clinical jaundice > 2.5 mg/dl
Icterus is the Greek term for jaundice.
It's level confirms jaundice, and used to assess
the prognosis.
It's level represents the balance between input
from production and hepatic removal of the
pigment.
Unconjugated hyperbilirubinemia is due to
overproduction
or
impaired
uptake
or
conjugation of bilirubin.
Conjugated
hyperbilirubinemia is due to
decreased excretion or backward leakage of the
pigment.
Normal serum gives a negative van den bergh
reaction.
PRINCIPLE OF THE REACTION:
The reagent is a mixture of equal volumes
of sulfanilic acid in dilute HCl and sodium
nitrite. (DIAZOTISED SULFANILIC ACID )
That diazotised sulfanilic acid reacts with
bilirubin to form a purple coloured
AZOBILIRUBIN.
Direct Positive: conjugated bilirubin gives a
purple color immediately on addition of the
reagent.
Indirect Positive: Purple color develops only
when the reagent and methanol are added.
Unconjugated bilirubin gives color only when
methanol is added.
BiPhasic: Purple color develops on addition of
reagent. Addition of methanol intensifies the
color.
Elevation of both unconjugated and
conjugated bilirubin
Indirect Positive----- Hemolytic jaundice
Direct Positive ----- Obstructive jaundice
Biphasic ----- Hepatic jaundice
Depending upon the etiology of hepatitis :
Conjugated hyperbilirubinemia:-
Viral hepatitis
Alcoholic hepatitis
Toxic hepatitis
Active cirrhosis
Genetic disease? Dubin johnson syndrome and
rotor's syndrome
Unconjugated hyperbilirubinemia:-
crigler najjar and gilbert's syndrome
physiological jaundice of newborn
ENTERO HEPATIC CIRCULATION
2.URINE UROBILINOGEN
UBG is formed in terminal ileum and colon from
conjugated Bb by Clostridium ramosum, helped by
E.coli.
UBG excreted in stool is called stercobilinogen. It is
converted by colonic bacteria to stercobilin which
imparts the normal brown colour of stools.
Hence in cholestatic jaundice stools are pale as Bb
can not reach the gut and hence stercobilin is not
formed.
About 20% of UBG is reabsorbed and undergoes
enterohepatic circulation.
Increase in UBG in urine is found in hepatitis as
damaged hepatocytes are not able to reexcrete the
UBG absorbed from gut. It is thus a good index of
hepatocellular dysfunction, often when other tests
are normal.
Urine UBG is increased in :
1)hepatitis 2)malignant disease of liver
3)cirrhosis 4)hemolytic anaemia
UBG is absent in :
1) complete biliary obstruction
2) severe bilirubin glucoronyl transferase
deficiency as seen in CN syndrome type I.
3.URINE BILE SALT
Bile salts are formed in the liver from cholesterol
They are excreted in bile
Facilitate absorption of fat from intestine
Constitute a substantial amount of bile in bilirubin
excretion and can be used in diagnosing cholestasis
Primary bile salts ? cholate and chenodeoxycholate are
produced in liver
Metabolised by bacteria in intestine
Produces secondary bile salts ? lithocholate,
deoxycholate and ursodeoxycholate
In cirrhosis ? reduced ratio of primary to secondary bile
salts
In cholestasis ? as secondary bile salts are not formed ?
so increased ratio of primary to secondary bile salts.
In normal condition ? renal excretion of bile
salts is negligible
In Hepatocellular jaundice, swollen liver cells
compress biliary canaliculi
Hence, there is intrahepatic obstruction of
biliary canaliculi
Bile salts cannot reach intestine, they are
regurgitated from liver into systemic
circulation and appear in urine
4.URINE BILIRUBIN
Bilirubin is not normally present in urine and
faeces 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.
Conjugated bilirubin in serum is raised in
hepatocellular and obstructive jaundice.
Therefore, bilirubin is present in urine in
hepatocellular and obstructive jaundice
Bilirubin in the urine may be detected even
before clinical jaundice is noted.
Recovering from jaundice urine bilirubin clears
prior to Sr bilirubin
5.DETERMINATION OF TOTAL PROTEIN ,ALBUMIN,
GLOBULIN & A:G RATIO
This yields most useful information in chronic
liver diseases.
Liver is the sole site for synthesis of most plasma
proteins except immunoglobulin (gamma
globulins)
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
A:G RATIO=1.5:1 to 2.5:1
Serum albumin comprises 60% of all plasma
proteins
Half-life of albumin is 14 to 21 days makes it
unreliable in acute liver failure
In infectious hepatitis:
quantitative estimations of albumin and
globulin may give normal results in the early
stages. qualitative changes may be present,
in early stage rise in -globulins and in later
stages -globulins shows rise.
cirrhosis or parenchymal liver disease:
The albumin is grossly decreased and the
globulins are often increased, so that A:G
ratio is reversed, is characteristically seen in
cirrhosis of liver.
6.PROTHROMBIN TIME
With the exception of F-VIII , all other
coagulation factors are synthesized in liver
Half life ranges from 6hrs for F-VII to 5 days for
fibrinogen
So their measurement is the single best measure
of hepatic synthetic function
Measured by Prothrombin time
Prothrombin vitamin K thrombin
?Marked increase in PT >5secs above the control
and not corrected by Vit K administration ? is a
poor prognostic sign in acute viral hepatitis and
other acute and chronic liver disease
ALANINE TRANSAMINASE (ALT)
7.SERUM TRANSAMINASE
ASPARTATE TRANSAMINASE (AST)
Liver enzymes are important markers of
hepatocellular damage & severity of liver
diseases.
AST
Heart, skeletal muscle, brain, pancreas, lung, RBC
and kidney.
20% cytosolic and 80 % mitochondrial
serum half life of 17 hrs.
ALT
ALT is more specific for liver
Low concentrations in kidney and skeletal muscles
serum half life of 47 hrs
DE RITI'S RATIO: THE AST:ALT RATIO
Normal ratio is 0.7 to 1.4.
In alcoholic hepatitis, the AST:ALT ratio is
always 2:1.
The ratio is usually <1 in patients with acute
and chronic non- alcoholic hepatitis.
q Most marked elevations of ALT and AST (>15
times normal) are seen in
? acute viral hepatitis
? toxin-induced hepatocellular damage (e.g.
carbon tetrachloride and
? centrilobular necrosis due to ischemia
(congestive cardiac failure).
Moderate elevations (5-15 times) occur in
Chronic hepatitis,
autoimmune hepatitis
alcoholic hepatitis
acute biliary tract obstruction
drug-induced hepatitis
q Mild elevations (1-3 times) are seen in
cirrhosis,
nonalcoholic steatosis
cholestasis.
Diagnostic value of transaminases
The first laboratory abnormality detected in
early phase of viral hepatitis is elevated
transaminases
In anicteric hepatitis and inapparent hepatitis
the only biochemical abnormality may be an
elevated ALT or AST.
Fluctuating levels of transaminases may be seen
in hepatitis C infection .
In hepatitis, elevation of transaminases
precedes that of bilirubin by about one week.
During recovery phase of viral hepatitis, there
is a steady fall in level of transaminases.
8. Alkaline phosphatase
Alkaline phosphatase (ALP) is synthesized in
liver, bones, intestine and placenta
In liver, ALP is synthesized by parenchymal cells
as well as epithelial cells of biliary canaliculi
Serum ALP is mildly raised in viral hepatitis due
to necrosis of parenchymal cells
A marked elevation in serum ALP occurs in
obstructive jaundice
The rise is due to increased synthesis of ALP
caused by irritation of epithelial cells of biliary
canaliculi
9.GAMMA GLUTAMYL TRANSPEPTIDASE ( GGT)
It is synthesized by epithelium of small bile
ductules and hepatocytes
GGT levels are higher in biliary tract disease
and cholestasis than in hepatocellular disease.
Rise in serum GGT is a sensitive indicator of
alcoholic hepatitis
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.
10.SPECIAL TESTS
A.Ceruloplasmin
Normal plasma levels - 0.2-0.4g/L
? Acute phase protein
Decreased in multiple conditions
1. Wilson's disease (Hepatolenticular
degeneration)
2. Menkes disease
3. Aceruloplasminemia
4. Copper deficiency
B.Blood ammonia
In advanced liver disease, liver may fail to
convert ammonia into urea
Increased blood ammonia
can cause hepatic encephalopathy
Measurement of blood ammonia helps in its
diagnosis and monitoring.
C.ALPHA -1 ANTITRYPSIN (-1 AT)
Major -1 globulin protein
Responsible for 90% of plasma tryptic
inhibitory capacity
-1 AT deficiency is a major cause of chronic
liver disease in children
Less commonly, of chronic liver disease
presenting in adulthood.
D.TRANSFERRIN
An iron transfer protein ( Normal-30-40%
saturated)
Its saturation is used as a screening test for
Hemochromatosis ( >60% saturated)
Decreased saturation is found in cirrhosis and
malnutrition.
E. ALPHA FETO PROTEIN
Normal component of fetal blood but
disappears few week after birth.
Mild elevation is seen in cirrhosis, acute and
chronic hepatitis
Higher concentration is seen in hepatocellular
carcinoma.
F. GALACTOSE TOLERANCE TEST
Galactose is almost exclusively metabolized by
the liver.
The liver function can be assessed by measuring
the utilization of galactose.
The subject is given intravenous administration
of galactose (about 300 mg/kg body weight).
Blood is drawn at 10 minute intervals for the
next 2 hours & galactose estimated.
In the normal individuals, the half-life of
galactose is about 10-15 minutes.
This is markedly elevated in hepatocellular
damage (infective hepatitis, cirrhosis).
G. BROMOSULPHTHALEIN DYE TEST
Bromosulphthalein is a dye used to assess the
excretory function of liver.
It is a non-toxic compound & almost exclusively
excreted by the liver (through bile).
BSP is administered intravenously (5 mg/kg body
weight) & its serum concentration is measured at
45 min & at 2 hrs.
In normal individuals, <5% of the dye is retained at
the end of 45 min.
Any impairment in liver function causes an
increased retention of the dye.
Increased plasma retention can result from
decreased excretory rate as seen in Dubin Johnson
Syndrome.
H. Mitochondrial Antibodies Test
The presence of these antibodies can
indicate
? primary biliary cirrhosis,
? chronic active hepatitis, and
? certain other autoimmune disorders.
11.TEST TO DETECT HEPATIC FIBROSIS
liver biopsy is the standard for the assessment of
hepatic fibrosis.
Need has arrived to go for non invasive tests.
Single
serum biochemical markers that
potentially reflect the activity level of hepatic
fibrogenesis - Hyaluronan.
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
hepatitis B, alcoholic liver disease, and
nonalcoholic steatohepatitis
ASCITES FLUID
THE SPECIAL "LFT"
PARACENTESIS
Tests
4 C's: Cells, Culture, Chemistry, Cytology
Cell count and differential, gram stain, culture,
albumin, total protein, glucose, LDH, cytology
Optional: amylase, bilirubin, Cr, TG, AFB cx +
adenosine deaminase
Calculation of SAAG
SAAG = [Serum albumin] ? [Ascites albumin]
What does the SAAG indicate?
If 1.1 g/dL, portal HTN is very likely (~97%
accurate1)
If < 1.1 g/dL, portal HTN is unlikely.
This post was last modified on 30 November 2021