Download MBBS LFT Lecture PPT

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