Download MBBS LFT Lecture PPT

1.

Jaundice

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2.

Alcoholic liver disease

3.

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Secondary metastasis to liver

4.

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Undiagnosed chronic illness

5.

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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disorders

Gauge 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 are

classified into following groups:

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BIOCHEMICAL CLASSIFICATION

1. 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 enzymes
I.

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 Protein


CLINICAL CLASSIFICATION

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...

Group I: Markers of liver dysfunction

Serum bilirubin: total = conjugated+

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Unconjugated

Urine: urobilinogen, bile salts and bilirubin

Total protein, serum albumin, globulin and

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albumin/globulin ratio

Prothrombin Time

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Group II: Markers of hepatocellular injury

Alanine 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 III

Transferrin

peptide

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-1Anti Trypsin

Bromsulphthalein

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test

Alpha Feto Protein

Anti-mitochondrial

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Blood ammonia

antibody test

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Galactose

tolerance 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 ability
to 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, it

diffuses 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 the
pigment.

Unconjugated hyperbilirubinemia is due to

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overproduction

or

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 bergh

reaction.

PRINCIPLE OF THE REACTION:

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The reagent is a mixture of equal volumes

of sulfanilic acid in dilute HCl and sodium
nitrite. (DIAZOTISED SULFANILIC ACID )

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That diazotised sulfanilic acid reacts with

bilirubin 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 of

reagent. 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 hepatitis

Active 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 is

converted 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 of

hepatocellular 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 transferase

deficiency as seen in CN syndrome type I.

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3.URINE BILE SALT

Bile 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 cholestasis

Primary 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 ursodeoxycholate

In 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 cells

compress 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 systemic
circulation 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 in

hepatocellular 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 plasma

proteins 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 2.5:1
Serum albumin comprises 60% of all plasma

proteins

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Half-life of albumin is 14 to 21 days makes it

unreliable 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 later
stages -globulins shows rise.

cirrhosis or parenchymal liver disease:

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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.

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6.PROTHROMBIN TIME

With the exception of F-VIII , all other

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coagulation factors are synthesized in liver

Half 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 time

Prothrombin 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 disease


ALANINE 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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ALT
ALT 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 is

always 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 obstruction

drug-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 in

early phase of viral hepatitis is elevated
transaminases

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In anicteric hepatitis and inapparent hepatitis

the only biochemical abnormality may be an
elevated ALT or AST.

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Fluctuating levels of transaminases may be seen

in 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 in

liver, 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 cells

A 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 encephalopathy
Measurement 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 tryptic

inhibitory 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 the

next 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 the

excretory 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 at
45 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 FIBROSIS

liver 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 that

potentially 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, and
nonalcoholic 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 deaminase

Calculation 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.