" Liver is the largest internal organ &largest gland in the
human body.
" Liver is at the epicenter of intermediary metabolism.
It performs versatile &massive biochemical pathways.
It destroys bacteria, inactivate antigens, detoxify harmful
chemicals.
Thus multiple &diverse functions of liver have an
impact on every tissue in the body.
Physiological functions of liver
" Intermediary metabolism
a. Carbohydrate metabolism
b. Lipid metabolism
C. Bile metabolsim and entero- hepatic circulation
d. Protein metabolism
Coagulation
Heme metabolism
Bilirubin metabolism
Xenobiotics metabolism
Storage
Endocrine functions
Immune &inflammatory response
Blood reservoir
Liver Function Tests
" Uses
" Todetect the presence of liver disease
" Todistinguish among diferent type of liver disorders
Toguage the extent of known liver damage
" Tofollow the response to treatment
Classification of LFTs
O
Tests based on detoxification and excretory functions
Serum bilirubin
Breakdown product of porphyrin ring of heme containing proteins
2fractions -conjugated (direct - 30%)
unconjugated (indirect -70%)
Normal total serum bilirubin 1 mg/dl
‘ in unconjugated fraction is rarely due to liver disease
Fractionate bilirubin
>15% direct <15% direct
Dubin Johnson syndr Evaluation for
Rotor's syndr hemolysis
-Ve +Ve
Grigler-Najar syndr Hemolysis
Gilbert's syndr
No further evaluation
required
Enzymes categories
Enzymes that reflect damage to hepatocytes
" Enzymes that reflect cholestasis
" Enzymes thatreflect damage to hepatocytes
- Aminotransferases
Aspartate aminotransferase (AST or SGOT): Liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, etc.
Alanine aminotransferase (ALT or SGPT): 1° in liver
" Sensitive indicators of liver cell injury
Normal levels <35-45 IUL
‘ in aminotransferases
. Mild - <250 IUN
- Any pathologic process that causes hepatocellular injury, e.g. hepatic
steatosis,alcohol or drug induced liver disease, chronic viral hepatitis,
cirrhosis, hemachromatosis
" Moderate-250-1000 IUN
- Disorder that produces hepatocellular necrosis
e.g. Acute viral hepatitis, drug induced hepatitis, exacerbation of
chronic hepatitis (alcoholic)
" Large- >1000 IUN
Viral or drug induced liver damage superimposed on ALD,
autoimmune hepatitis
Extreme ->2000IUN (acetaminophan),
from drugs viral
necrosis, usually (shock liver), acute
Massive hepatic ischemic hepatitis
halothane hepatitis, toxins,
hepatitis
QUOTIENT
ASTIALT ratio - DERITIS
- Normal -1 or slightly > 1
without cirrhosis
< - non-alcoholic steatosis or hepatitis
" 2-4-ALD
" >4 Wilsonian hepatitis
ASTIALT not ‘ in purely obstructive disorder except
Acute biliary obstruction caused by passage of
gallstones to CBD
" LDH
Normal level -25-100 IU/L
Massive but transient - Ischemic hepatitis
Massive, sustained- Malignant infiltration of liver
Other causes of ‘ LDH
Hemolysis
Renal infarction
Acute stroke
Myocardial damage
Skeletal muscle injury
Glutathione S transferase
Relatively sensitive and specific test for detecting drug-induced
hepatocellular injury
Plasma t 90 min, rapidly released into the circulation following
hepatocellular injury
Plasma GST (0soenzyme B)-reveal time course of hepatocellular
injury from onset to resolution
GST-located in the centrilobular region (zone 3), where hepatocytes
are mostsusceptible to injuries from hypoxia and reactive drug
metabolism
Bromosulphathein excretion test
" BSP dye- same mechanism as bilirubin
-binding
-conjugation
-excretion
BSP - ily 45 mins- levels in venous blood
Normally- <5%.
Slightly higher in old age
Sensitive test to detect mild impairement of liver
Enzymes reflecting cholestasis
Alkaline phosphatase- present in cels of the bile duct
" Isoenzymes- bone, liver, intestine, placenta , kidney, leukocytes.
Normal levels- 42-122 IUIL
-3-13 KA units/dl
Non-pathological T Pathological T
Age >60 yrs 1° biliary cirrhosis
Bld group-O &B Choledocholithiasis
Growing children & Hepatic malignancy
adolescents 1° & 2°
Late in normal Paget's disease
pregnancy
T in serum ALP inan apparently healthy pt.
Fractionate the ALP to identify source of isoenzyme
ALP from different tissues differ in susceptibility inactivation by
heat
. Measure - 5' NT, GGT
" 5' NT
" Sensitive and specific for hepatobiliary disorders (HBD)
" Normal pregnancy, bone growth and bone diseases do not affect 5' NT
" In pts with HBD,changes in ALP are usually followed by similar
changes in 5' NT
" GGT
Inducible microsomal enzyme. Nlevels-5- 40 IU/L.
" Less specific than 5' NT as a marker for HBD
Unlike 5' NT, GGT may be released from many sites beside the
hepatobiliary tree
>Bone -important source of ALP, has little GGT thus GGT useful for
differentiating hepatic &osseous sources of ALP
OTests for bio-synthetic function of the liver
" Estimation of plasma proteins
Tests for reversal of A:G ratio
" Tests for coagulability of blood
Plasma protein Normal levels
Total 6.4-8.3 g%
S. Albumin 3-5g%
Serum globulin 2-3 g%
Serum fibrinogen 0.3 g%
Serum prothrombin 40 mg%
A:G ratio 1.7:1
" Serum albumin
" S. albumin <3 g/dl > suspect chronic liver disease
" Hypoalbuminemia - not specific for liver disease
- Protein malnutritionof any cause
- Protein losing enteropathies
- Nephrotic syndrome
Chronic infections
- Burns
Reversal of A: Gratio -’ chronic liver dysfunction.
" Serum globulin
T in gamma globulin > chronic liver disease
lg M-‘1 Primary biliary cirrhosis.
" IgA- Alcoholic liver disease.
" lg G- 1tAuto immune hepatitis.
" Thymol turbidity test
Test for reversal of A:G ratio
Marked T turbidity liver insufficiency
" Coagulation factors
Factor I, I1, V, VI, VI
" Short ti/2-single best measure of acute hepatic synthetic function
Tests -PT- N 11-16 sec
- PTTK-N30- 40 sec
Prognostic value
PT>5 sec above control- indicative of poor prognostic sign in acute
viral hepatitis.
Tin hepatitis, cirhosis, disorders leading to vit Kdeficiency such as
obstructive jaundice or fat malabsorption
OImmunological tests
Antibodies to specific etiologic agents
HBV- HBSAg ,HBcAg. HBeAg
Antibody to Entamoeba histolytica
Antibody to CMV, HCV, EBV
Non specific antibodies
Antimitochondrial antibody- PBC
Antismooth muscle antibody- Auto immune hepatitis
pANCA- Primary sclerosing cholangitis
" Serum tumor markers
afeto-protein -‘ in HCC.
" Hepatobiliary imaging
" USG, CT Scan - 1st line investigation
ERCP, PTC- visualization of biliary tract
Doppler USG& MRI- hepatic vasculature &heamodynamics
CT& MRI- hepatic masses &tumours
" Others
FNAC
" Biopsy - percutaneous needle liver biopsy
a) VIM -SILVERMAN (Cutting )needle
b) MENGHINI'S (aspiration ) needle
" Indications
Unexplained hepatomegaly
- Cholestasis of unknown cause
- Persistent abnormal LFTs
- Infiltrative disorders- sarcoidosis, tuberculosis
- Pyrexia of unknown origin
- Primaryl metastatic liver diseases
Blood tests &DID of hepatic dysfunction
Bilirubin overload Parenchymal |cholestasis
(hemolysis) dysfunction
Aminotransferases Normal ‘(may be Nor . in N( may be tin
advanced stages advanced stages)
ALP Normal Normal Increased
serum bilirubin ‘ unconjugated ‘ conjugated ‘ conjugated
Serum proteins Normal Decreased N(may be <in
advanced stages)
Prothrombin time Nomal (may be Nin early N(may be prolonged in
stages) advanced stages)
Blood urea nitrogen Nomal N (may be in Normal
advanced stages)
Sulfobromophthalein Normal Retention Normal or retention
indocyanine green
Shortcomings of LFTs
Can be normal in pts with serious liver disease and
abnormal in pts with diseases that do not affect the liver
Rarely suggest a specific diagnosis
Only categorises into hepatocelular or cholestatic
Expected Questions
SAQ - 4 Marks
1. Liver function tests
2. Enzymes in liver disease
3. Liver biopsy
