liver, liver disease

1. LIVER FUNCTION TEST

2. FUNCTIONS OF LIVER
Metabolic
function
Excretory
function
Synthetic
fuction
Detoxification
function
Storage
function

3. Classification of LFT
Tests based on excretory function
Serum bilirubin
Urine bilirubin
Urine and faecal urobilinogen
Urine bile salts
Dye excretion tests

4. Tests based on detoxification function
Hippuric acid test
Determination of blood ammnia
Tests based on synthetic function
Plasma protein
Prothrombin time
Tests based on metabolic function
Tests related to carbohydrates metabolism, lipid metabolism,
protein metabolism.

5. Enzymes in diagnosis of liver disease
SerumTransaminases (ALT, AST)
Serum ALP
Glutamate Dehydrogenase
5’-Nucleotidase
γ- GlutamylTransferase
Other parameters
Bilirubin (T and D)

6. Biochemical Differentiation of 3 types of jaundice
Sample Biochemical Parameters Types of Jaundice
Pre-hepatic Hepatic Post-hepatic
Blood Serum Bilirubin (T)
Types of Bilirubin
Transaminases (esp. ALT)
ALP
5’-Nucleotidase
ProthrombinTime (PT)
Effect of Parental vitamin
K on PT
Unconjugated
N
N
N
N
No effect
Mixed
Very High
Moderately Increased
Moderately Increased
Slight Prolonged
Remains Prolonged
Conjugated
Moderately Increased
Very High
Very High
Slight Prolonged
Normalizes
Urine Urobilinogen
Bilirubin
Bile Salts
Absent
Absent
Normal /
Absent
Absent
Absent or Decreased
Present/ Increased
Present/ Increased
Stool Stercobilinogen Present/
Increased
Decreased Absent or Decreased

7. Serum enzyme assay in clinical practice
Helps in making the diagnosis/differential diagnosis/ early
detection of a disease.
Helps in ascertaining prognosis of a disease.
Helps in ascertaining the response to drugs in a disease.
Also help in ascertaining the time course of disease.

8. TRANSAMINASES
Enzymes required for the exchange
of the alpha amino group between
one alpha amino acid and another
alpha keto acid forming new alpha
amino acid.
The two aminotransferases have
greatest clinical significance.
The enzymes require Pyridoxal
phosphate as co-enzyme.

9. Aspartate aminotransferase (AST)
Both these enzymes are found in most tissues , but the relative amounts
vary .
Heart muscles are richer in AST, whereas liver contains both but more of
ALT.
AST is released into the circulation after injury or death of cells.
Normal level:
Infants levels approximately twice the adult level and the decline to adult
levels by approximately 6 months of age.

10. Reflects damage to the hepatic cells but is less specific for liver disease. It can
also be released with heart muscle disorders like damage to the heart muscle,
as in myocardial infarction
 acute hepatocellular disorders "viral hepatitis, cirrhosis”.
 acute hemolytic anemia
 acute pancreatitis or inflammation of the pancreas
 Heart attack
 recent surgery
 severe burns
 muscle injury

11. Alanine Aminotransferase (ALT)
Converts alanine + α-ketoglutarate to pyruvate and glutamate
ALT is predominantly found in the cytoplasm of hepatic parenchymal cells
and considered to be liver specific.
it is also active in the heart, skeletal muscle, pancreas, and the kidney.
ALT activity in the liver is about 3,000 times higher than its activity in the
serum. ALT will be excreted into the blood only if cells are damaged

12. Elevated levels of ALT:
 alcoholic liver disease
 Hepatitis or inflammation of the liver
 cholestasis or congestion of the bile ducts
 cirrhosis or scarring of the liver with loss of function
 tumor of the liver
 use of medicines or drugs toxic to the liver
Often higher than AST with liver damage and tend to remain elevated
longer
Remains normal in AMI

13. AST and ALT is in the different distribution of the hepatocytes.
ALT exists primarily in the cytoplasm of liver cell. if there is a slight liver cell damage,
ALT firstly leak into the bloodstream.
AST mainly in the mitochondria of liver cells. If there is a slight liver cell damage,
AST don`t leak into the bloodstream.
Significantly higher AST indicates injuries to mitochondria of liver cells which
indicate severe liver damage, such as cirrhosis, chronic severe hepatitis, Alcohol-
induced hepatitis, drug-induced hepatitis.
attention to AST and ALT ratio should be given; if the ALT / AST < 1, note a serious
liver cell injury, need timely treatment.
AST>ALT in:
 alcoholic hepatitis and cirrhosis,
 metastatic cancer of the liver
 non-biliary cirrhosis,
while ALT>AST in:
 viral and drug hepatitis,
 chronic hepatitis C
 hepatic obstruction.

14. In viral hepatitis and other forms of liver disease associated with hepatic
necrosis, serum AST and ALT levels are elevated even before the clinical signs
and symptoms of disease (such as jaundice) appear.
Levels for both enzymes may reach values as high as 100 times the upper
limit of the reference, although 20- to 50- fold elevations are most frequently
encountered.
Peak values of transaminase activity occur between the seventh and 12th
days; activities then gradually decrease, reaching normal levels by the third
to fifth week if recovery is uneventful.

15. Glutamate Dehydrogenase (GDH)
 Mainly present in the liver, heart, muscle and kidneys
 Normally present in trace amount in blood
 Increased activity seen in hepatocellular damage
5’ Nucleotidase
 Phosphatase that acts only on nucleotide-5’-phosphate like AMP
 Normal range: 2-17IU/L
 Increased activity 2-6 times seen in some hepatobiliary diseases which may
be due to extrahepatic (stone, tumor, fibrosis osbstruction) or intrahepatic
(cholestasis, biliary cirrhosis).

16. GlutamylTransferase/  GlutamylTranspeptidase ( GT)
Transfers  Glutamyl group
Found mainly in biliary ducts of the liver, kidney and pancreas.
Normal range: 10-47IU/L
-GT increased in liver diseases especially in obstructive jaundice.
-GT levels are used as a marker of alcohol induced liver disease and in liver
cirrhosis
Enzyme activity is induced by a number of drugs and in particular alcohol.
.

17. Alkaline phosphatase
(EC 3.1.3.1; orthophosphoric-monoester phosphohydrolase)
Group of enzymes that hydrolyze organic phosphates at high pH 9.0-10.5 and is activated
by Mg2+ & Mn.
Nonspecific enzyme.
Zn is a constituent of ALP
Half-life= 10 days
produced by osteoblasts of bone and localized in cell membranes (ecto-
enzyme).
Also produced by epithelial cells of biliary canaliculi & obstruction of bile
with consequent irritation of epithelial cells leads to secretion of ALP into
serum

18. Isoenzymes
Major isoenzymes are found in Liver, bone, placenta, and then
intestinal fraction
Liver isoenzyme (fastest): Its level rises in extra hepatic biliary
obstruction.This liver iso-enzyme forms about 25% of total ALP
Bone isoenzyme: Increases due to osteoblastic activity and is normally
elevated in children during periods of active growth .This constitutes about
50% of normal ALP activity.
Placental isoenzyme: Rises during last 6 weeks of pregnancy. Normal
level is only 1% of the total ALP
Intestinal isoenzyme (slowest): About 10% of plasma ALP are of
intestinal origin Inhibited by phenylalanine. Rise occurs after a fatty meal.

19. Normal range-40-125 U/L.
In children, Increased levels are seen, due to increased osteoblastic activity. Mild
increase is noticed during pregnancy due to production of placental isoenzyme
People over age 60 can have a mildly elevated ALP.
Individuals with blood types O and B can have an elevation of the serum alkaline
phosphatase after eating a fatty meal due to the influx of intestinal alkaline
phosphatase into the blood.
Moderate (2-3) increase: is seen in hepatic diseases such as infective hepatitis,
alcoholic hepatitis or hepatocellular carcinoma.

20. Very high levels (10-12 times of upper limit)
may be noticed in extrahepatic obstruction (obstructive jaundice) caused by
gallstones or by pressure on bile duct by carcinoma of head of pancreas
Drastically high levels (10-25 times of upper limit): seen in bone
diseases where osteoblastic activity is enhanced

21. ACID PHOSPHATASE (ACP)
Group of enzymes that hydrolyses phosphoric acid ester at pH between 4 and
6
present in prostate gland, liver, spleen and RBC.
The main source ofACP is prostate gland and so can be used as a marker for
prostate disease.
Normal serum value for ACP is 2.5-12 U/L.
Increased in prostate cancer and highly elevated in bone metastasis of prostate
cancer.
Very helpful in follow-up of treatment of prostate cancers.

22. PANCREATIC FUNCTIONTESTS

23. AMYLASE
Is the digestive enzymes from the pancreas and salivary glands to digest
complex carbohydrates; splits starch to maltose
Activated by calcium, chloride and fluoride ions.
Products of different genes located in chromosome1
Normal serum value is 50-120 U/L
Increased about 1000 times in acute pancreatitis which is a life-threatening
condition. The peak values are seen between 5-12 hours after the onset of
disease and returns to normal levels within 2-4 days after the acute phase
has subsided.
.

24.  Moderate increase in serum levels are seen in chronic pancreatitis,
mumps (parotitis), obstruction of pancreatic duct and in renal disease.
 It is used as a marker to detect acute pancreatitis and appendicitis

25. Lipase
 Hydrolyses triglyceride to beta-monoglyceride and fatty acid. present in
pancreatic secretion.
 Normal serum range is 0.2-1.5 U/L
 The level in blood is highly elevated in acute pancreatitis and persists
for 7-14 days.
 Remains elevated longer than amylase.
 Not increased in mumps. Therefore, lipase estimation has advantage
over amylase.
 Moderately increased in carcinoma of pancreas, biliary diseases and
perforating peptic ulcers.

26. Pancreas
 Located in the abdominal cavity adjacent to the upper part of the small intestine
 Endocrine function by islets of Langerhans to produce hormones
 Exocrine function by acinar cells to produce pancreatic juice
 Exocrine function regulated by hormonal control and nervous control
Pancreatitis
 Condition in which activated proteolytic enzymes as liberated from acinar cells
into the surrounding pancreatic tissue and attack the pancreas itself.
 This self-digestion often results in reduced output of pancreatic juice
 The condition may be acute or chronic

27. Biochemical Tests to assess Exocrine functions
Volume and Bicarbonate of the Pancreatic Juice
 Assessed by intubating the duodenum and subjecting the pancreas to stimulation
with a test meal, secretin or pancreozymin.
 After duodenal contents are aspirated, patient is given secretin (1 unit/kg body
weight) intravenously and aspirate is examined for volume, bicarbonate content
and amylase activity.
 Pancreatitis: reduction in volume of pancreatic juice as well as bicarbonate
 Milder Pancreatitis: volume of pancreatic juice and bicarbonate remain fairly
normal but amylase activity is reduced.
 Chronic Pancreatitis: Patient unable to secrete juice of high bicarbonate content
 Carcinoma of head of pancreas obstruct overall volume flow.

28. Enzymes in serum/urine
Serum and urinary Amylase:
 activity increased in acute pancreatitis.
 Rise starts within hour of the onset of pain and rises to 10 fold normal value.
 Remains increased upto 48 hrs and return normal after 4-8 days.
 Urinary amylase is also increased
Serum Lipase:
 activity rises slower that that of amylase sometimes as late as 24-48 hrs and
reaches peak on the forth day.
 May remain elevated for longer period than amylase.
 Serum Lipase compared to serum amylase is elevated more often in pancreatic
carcinoma.

29. Serum Elastase:
 Pancreatic proteolytic enzyme for scleroproteins found in connective tissues
 Produced in acinar cells as zymogen
 Activated by trypsin
 Significance in later stage of acute pancreatitis or relapse or cystic complications
of chronic pancreatitis.
 Remains elevated longer than amylase.