2. FUNCTION OF THE LIVER
INDICATION OF THE LIVER FUNCTION TEST
CLASSIFICATION OF THE LIVER FUNCTION TEST
CLINICAL CASE
SERUM ENZYME THAT REFLECT DAMAGE TO
HEPATOCYTES
LOCATION OF ENZYMES IN LIVER
ENZYME INDICATING HEPATO CELLULAR DAMAGE
ASPARTATE TRANSAMINASE
(AST/SGOT)
ELEVATED LEVELS OF AST
2
3. ALANINE TRANSAMINASE(ALT/SGPT)
ELEVATED LEVELS OF ALT
AST:ALT RATIO
CLINICAL SIGNIFICANCE OF THIS RATIO
ENZYME THAT DETECT CHOLESTASIS
ALKALINE PHOSPHATASE(ALP)
Υ-GLUTAMYL TRANPEPTIDASE(GGT)
5’-NUCLEOTIDASE
ABNORMAL LIVER ENZYME PROFILE
TABLE OF DIAGONOSTIV TESTS
CLINICAL CASE
OBSTRUCTIVE JAUDICE
DIFFERENTIAL DIAGNOSIS OF JAUNDICE
TAKE HOME MESSAGE
BIBLIOGRAPHY
3
4. Synthetic functions : synthesis of plasma proteins,
cholesterol, triacyl glycerol, lipoprotein
Metabolic function: protein metabolism, ketogenesis, TCA
cycle, production of ATP
Detoxification & excretion: ammonia to urea, bilirubin,
cholesterol, drug metabolites.
Homeostasis : blood glucose regulation
Storage function: Vitamin A,D,K,B12
Production of bile salts
4
5. Jaundice
Suspected liver metastasis
Alcoholic liver disease
Any undiagnosed chronic illness
Annual checkup of diabetic patients
Coagulation disorders
Therapy with statins to check hepatotoxicity
5
6. GROUP I -TEST OF HEPATIC EXCRETORY
FUNCTION
i. SERUM- BILIRUBIN;TOTAL ,CONJUGATED,UNCONJUGATED
URINE-BILE PIGMENTS, BILE SALTS AND UROBILINOGEN
6
GROUP II-LIVER ENZYME PANEL
ALT
AST
ALP
GGT
8. GROUP I:MARKERS OF LIVER DYSFUNCTION
SERUM BILIRUBIN, TOTAL,CONJUGATED
URINE;BILE PIGMENTS ,BILE SALTS AND UBG
TOTAL PROTEIN,SERUM ALBUMIN & A/G RATIO
PROTHROMBIN TIME
BLOOD AMMONIA WHEN INDICATED
8
10. TEST MEAN VALUE RANGE
NORMAL VALUE
TOTAL
BILIRUBIN(mg/
DL)
8.5 1.5-15 0.2-0.9
SGOT(U/L) 159.6 63-204 5-35
SGPT(UI/L) 229.2 76-394 5-45
ALKALINE
PHOSPHATASE
(UI/L)
432.8 226-792 250
γ GTP(UI/L) 694.9 352-1455 5-30
UNCONJUGATED
BILIRUBIN (mg/dl)
4 3-5 0.2-0.7
CLINICAL STUDY OF CASE OF A 19 YEAR OLD
FEMALE HAVING FOLLOWING
DIAGNOSIS
10
UROBILINIGEN
(mg/dL
4.5 3.5-6 0.2-1
15. A large number of enzyme estimations are available which are
used to ascertain liver function.
They are be divided into two groups:
A). Enzymes indicating hepatocellular damage.
B). Enzymes indicating cholestasis (obstruction).
In liver cells injury , damage to the membrane of cells &
organelles allows intracellular enzymes to leak into the blood
15
17. Normal range: 5-35 U/L.
AST is found in both cytoplasm & mitochondria
AST/GOT also reflects damage to the hepatic cells & is less
specific for liver disease.
It is a cardiac marker.
AST help diagnose various heart, muscle or brain
disorders, such as a myocardial infarct (heart attack).
17
18. Acute hemolytic anemia
Cirrhosis of the liver
Hepatitis
Acute pancreatitis or inflammation of pancreas
Acute renal failure or loss of kidney function.
Heart attack
Primary muscle disease
Recent surgery
18
19. Normal Range: 5-40 U/L.
ALT is a cytoplasmic enzyme.
The activity of these enzymes is low in normal serum.
ALT is specific for liver disease.
Its elevations favor liver cell necrosis as a cholestasis.
19
20. Alcoholic liver disease
Cancer of liver
Hepatitis or inflammation of the liver
Noncancerous tumor of the liver
Use of medicines or drugs toxic to the liver
Cirrhosis or scarring of the liver
Death of liver tissue.
20
21. • Normal ratio is 0.7 to 1.4
• Useful in Wilson disease, chronic liver disease and alcoholic
liver disease
• AST/ALT ratio of > 2:1 is suggestive of and >3:1 is highly
suggestive of Alcoholic liver disease
• AST in Alcoholic live disease is rarely >300 U/L.
• ALT is usually normal in alcoholic liver disease ; can be sometimes
low due to an alcohol induced deficiency of pyridoxal phosphate
• AST/ALT <1 is seen in viral hepatitis.
21
23. • mAST/total AST ratio – marker of chronic alcohol
consumption
• This distinguishes those who consume excess alcohol
from normal subjects irrespective of the presence or
absence of liver disease
23
25. ALP occurs in all tissues, especially liver, bone, bile duct, kidney &
the placenta.
The ALP used to help diagnose certain liver diseases and bone
disorders.
Normal range: 30 - 115 U/L
ALP is a hydrolase enzyme responsible for removing phosphate
groups from many types of molecules, including nucleotides &
proteins.
Levels are significantly higher in growing children.
A rise in serum ALP , usually associated with elevated serum
bilirubin is an indicator of biliary obstruction (obstructive/post
hepatic jaundice).
ALP is also elevated in cirrhosis of liver & hepatic tumors.
25
26. Normal range: 5-50 U/L
This is a microsomal enzyme widely distributed in body tissues,
including liver.
Measurement of γ - glutamyl transpeptidase (GGT) activity provides
a sensitive index to asses liver abnormality.
Serum GGT is highly elevated in biliary obstruction & alcoholism.
GGT elevation parallels than of ALP.
Increased level of GGT are observed in chronic alcoholism ,pancreatic
disease ,MI ,renal failure ,diabetes mellitus.
Several drugs (e.g. phenytoin) induce (liver synthesis) & increase this
enzyme in circulation.
26
27. Normal range: 2-15 U/L
The serum activity of 5'-nucleotidase is elevated in
hepatobiliary disease & this parallels ALP.
It is highest in post-hepatic obstructive jaundice.
The 5'-nucleotidase is normal in patients with bone
disease where as serum ALP increased .
27
29. TEST MEAN VALUE RANGE
NORMAL VALUE
TOTAL
BILIRUBIN(mg/
DL)
8.5 1.5-15 0.2-0.9
SGOT(U/L) 159.6 63-204 5-35
SGPT(UI/L) 229.2 76-394 5-45
ALKALINE
PHOSPHATASE
(UI/L)
432.8 226-792 250
γ GTP(UI/L) 694.9 352-1455 5-30
UNCONJUGATED
BILIRUBIN (mg/dl)
4 3-5 0.2-0.7
CLINICAL STUDY OF CASE OF A 19 YEAR OLD
FEMALE HAVING FOLLOWING
DIAGNOSIS
29
UROBILINIGEN
(mg/dL
4.5 3.5-6 0.2-1
30. Function test Pre-hepatic Jaundice Hepatic Jaundice Post-hepatic Jaundice
Total bilirubin Normal / Increased Increased
Conjugated bilirubin Normal Increased Increased
Unconjugated
bilirubin
Normal / Increased Increased Normal
Urobilinogen Normal / Increased Increased Decreased / Negative
Urine Color Normal
Dark (urobilinogen +
conjugated bilirubin)
Dark (conjugated
bilirubin)
Stool Color Normal Normal/Pale Pale
Alkaline phosphatase
levels
Normal
Increased
Alanine transferase
and Aspartate
transferase levels
Increased
Conjugated Bilirubin
in Urine
Not Present Present
Splenomegaly Present Present Absent
Table of diagnostic tests
30
31. 31
Conjugated bilirubin is increased in blood & it is excreted
in urine. If there is complete obstruction, UBG will be
decreased in urine or even absent.
In total obstruction of biliary tree, the bile doesn’t enter
the intestine. Since no pigments are entering the gut, the
feces become clay coloured.
Van den Bergh test is direct positive as conj. bilirubin is
elevated.
32. Vital liver enzymes
normal Serum level of the enzymes
Diseases associated with the liver
Elevated level of enzymes in liver diseases
32
33. REFERENCES FROM
◦ TEXTBOOK OF BIOCHEMISTRY (for medical students)
– DM Vasudevan
◦ TEXTBOOK OF MEDICAL BIOCHEMISTRY – MN
Chatterjee
33