• Regulates bilirubinmetabolism by secretion and excretion
of bilirubin.
EXCRETORY
FUNCTIONS
• Synthesis of albumin, globulins and coagulation proteins,
triglycerides, cholesterol, lipoproteins, and primary bile
acids.
• Albumin maintains osmotic pressure of plasma.
SYNTHETIC
FUNCTION
• Liver regulates carbohydrate, lipid and protein
metabolism.
METABOLIC
FUNCTIONS
3.
• Iron, glycogenand vitamins
STORAGE
FUNCTION
• Ammonia
DETOXIFICATION
FUNCTION
• During fetal life, hematopoiesis occurs in the liver.
• Liver is the major organ for catabolism of steroid
hormones.
MISCELLANEOUS
• Liver functiontests are the various laboratory tests that are used
to:
1. Screen for liver disease;
2. Identify the nature of liver disease (hepatocellular,
cholestatic, or infiltrative);
3. Assess severity and prognosis of liver disease;
4. Follow up the course of liver disease.
6.
• The term‘liver function tests’ is a misnomer since most of these tests are
used for identification of liver disease, its severity, and its type and do not
necessarily assess liver function.
• These tests are not specific for liver disease and are abnormal in various
non-hepatic conditions.
• Therefore, laboratory tests should be selected and interpreted in the
context of clinical features and other investigations.
• An isolated abnormality of a single liver function test usually means a
non-hepatic cause.
• If several liver function tests are simultaneously abnormal, then hepatic
etiology is likely.
8.
LIVER FUNCTION TESTS
1.Tests that assess excretory function of the liver:
• Bilirubin in serum and urine, and urobilinogen in urine and feces.
2. Tests that assess synthetic and metabolic functions of the liver:
• Serum proteins, serum albumin, serum albumin/globulin (A/G) ratio,
prothrombin time (PT), and blood ammonia level.
3. Tests that assess hepatic injury:
• Serum alanine aminotransferase (ALT), serum aspartate aminotransferase
(AST), serum alkaline phosphatase, serum GAMMA-glutamyl transferase
(GGT).
4. Tests that assess clearance of exogenous substances by the liver:
• Bromosulphthalein excretion test.
9.
Tests that assessexcretory function of the liver:
BILIRUBIN
• Normal serum bilirubin is less than 1 mg/dl.
• There are two types of bilirubin in plasma:
unconjugated (indirect) 90% and conjugated (direct) 10%.
• Conjugated bilirubin is weakly bound to albumin, is water-soluble, and can be
excreted in urine.
• Unconjugated bilirubin is tightly bound to albumin and is water-insoluble.
• There are two methods for estimation of serum bilirubin:
1.Diazo Method
2.Spectrophotometry
10.
DIAZO METHOD
• Directbilirubin (Conjugated bilirubin): It reacts directly with diazo
reagent.
• Indirect bilirubin (Unconjugated bilirubin): It reacts with diazo reagent in
the presence of alcohol.
11.
JAUNDICE
• Jaundice refersto yellow discoloration of skin, sclera, and mucous
membranes due to increased level of serum bilirubin more than 2.0
mg/dl.
12.
UNCONJUGATED
HYPERBILIRUBINEMI
A
Hemolysis
Resorption of alarge
hematoma
Ineffective erythropoiesis
Gilbert’s syndrome and
Crigler-Najjar syndrome.
Physiologic jaundice of
newborn
MIXED
(CONJUGATED +
UNCONJUGATED)
HYPERBILIRUBINEMI
A
CONJUGATED
HYPERBILIRUBINEMI
A
Hepatitis
Cirrhosis
Cholestasis
Drugs (anabolic steroids,
oral contraceptives)
Dubin-Johnson syndrome,
and Rotor syndrome
Viral / Alcoholic
Hepatitis.
16.
TESTS WHICH ASSESSSYNTHETIC AND METABOLIC
FUNCTIONS OF LIVER
SERUM ALBUMIN AND PROTHROMBIN TIME
• Hypoalbuminemia and a prolonged prothrombin time indicate severe
functional impairment of liver.
Total serum proteins in adults 5.5 to 8.0 gm/dl.
Serum albumin 3.5 to 5.0 gm/dl.
Serum albumin comprises about 60% of total serum proteins.
17.
• Tests forproteins in liver disease:
1. Total serum proteins
2. Serum albumin
3. Calculation of serum albumin / globulin ratio
4. Serum protein electrophoresis.
• Serum albumin level is low in chronic liver disease (cirrhosis) fall in serum
albumin level correlates with severity of ascites.
• In cirrhosis and in chronic active hepatitis, serum gamma globulins are
increased due to inflammation.
• Low albumin and raised gamma globulins in serum cause reversal of
albumin/globulin ratio.
PROTHROMBIN TIME (PT)
•Most of the coagulation proteins are synthesized in the liver.
• Vitamin K is required for the synthesis of factors II, VII, IX, and X.
• Synthesis of these factors is deficient in hepatocellular disease.
• In obstructive jaundice, vitamin K (a fat-soluble vitamin) cannot be
absorbed due to the absence of bile in the intestine.
• PT measures three out of four vitamin K-dependent factors (II, VII, and X)
and is prolonged in hepatocellular disease and in obstructive jaundice.
20.
• BLOOD AMMONIAis mainly derived from gastrointestinal tract.
• In the intestine, bacterial enzymes act on nitrogen containing foods to produce
ammonia, which is carried to the liver via portal vein.
• In the liver, ammonia is converted to non-toxic urea in the urea cycle.
• Increased blood ammonia levels are seen in:
1. Fulminant hepatic failure
2. Cirrhosis
3. Reye’s syndrome
4. “Shunting” of portal blood to systemic circulation
5. Gastrointestinal hemorrhage (there is increased
production of ammonia from blood proteins by
bacterial enzymes).
6. In hepatic disease, gastrointestinal hemorrhage is
associated with increased risk of hepatic
encephalopathy.
7. Inherited deficiencies of urea cycle enzymes.
21.
TESTS WHICH ASSESSHEPATIC INJURY
(LIVER ENZYME STUDIES)
1. Serum aspartate aminotransferase or AST / serum glutamic-oxaloacetic
transaminase or SGOT
2. Serum alanine aminotransferase or ALT / serum glutamic-pyruvic
transaminase or SGPT
3. Serum alkaline phosphatase or ALP
4. Gamma-glutamyl transferase or GGT
22.
SERUM AMINOTRANSFERASES
• Sensitivemarkers of acute hepatocellular injury.
• ALT is a cytosolic enzyme and AST is both cytosolic and mitochondrial.
• Normally, aminotransferases are present in serum at a low level.
• When necrosis or death of cells containing these enzymes occurs, aminotransferases are
released into the blood and their concentration in blood increases.
• This level correlates with extent of tissue damage.
• 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).
23.
SERUM ALKALINE PHOSPHATASE(ALP)
• In cholestasis, accumulated bile acids dissolve canalicular side of
hepatocyte membrane and enzymes are released in blood.
• Therefore, diseases that affect mainly hepatocyte secretion have elevated
levels of ALP.
• Measurement of ALP is helpful in differentiation of hepatocellular
jaundice from cholestatic jaundice
24.
HEPATOBILIARY CAUSES OFINCREASED ALKALINE PHOSPHATASE
• Bile duct obstruction (cancer of head of pancreas, stone in common bile
duct, stricture of bile duct, biliary atresia)
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• Infiltrative diseases of liver (granulomatous diseases like tuberculosis or
sarcoidosis, amyloidosis, cysts, primary or secondary cancer)
25.
SERUM GAMMA-GLUTAMYL TRANSFERASE(GGT)
• High levels of this enzyme are present in liver, pancreas, kidney, and
prostate.
• Estimation of this enzyme is particularly useful in following liver diseases:
1.Alcoholism
2.Cholestasis
3.Recovery in acute hepatitis
26.
5’-NUCLEOTIDASE (5’-NT)
• 5’-NTis present in liver as well as in various other tissues.
• It is located mainly along the cell membrane.
• Estimation of 5’-NT is helpful in deciding whether increased ALP is due
to liver disease or due to increased osteoblastic activity in growing
children.
27.
TESTS THAT ASSESSCLEARANCE OF EXOGENOUS
SUBSTANCES FROM THE LIVER
• Some synthetic dyes, when introduced into the body, are rapidly removed
from the blood stream by the liver and excreted into the bile.
• Disappearance of these dyes from the blood is dependent on adequate
hepatic circulation, normal hepatocyte function, and uninterrupted bile
flow.
• Three synthetic dyes are commonly employed to test liver function:
1. Bromosulphthalein (BSP),
2. Indocyanine green (used by surgeons before resecting liver for hepatocellular
cancer)
3. Rose Bengal.
• However, because of the risk of adverse reactions and advent of more
sensitive tests for detection of liver disease, dye excretion tests are
nowadays rarely used.
28.
A STEPWISE APPROACHCONSISTS OF LABORATORY TESTS FOR:
1. Presence of liver disease: History, physical findings, and liver function
tests.
2. Nature of liver disease: whether hepatocellular (cell injury) or cholestatic.
3. Specific cause of liver disease
4. Assessment of severity of liver disease
29.
LIVER DISEASES CANBE BROADLY CLASSIFIED INTO TWO
TYPES:
1. Hepatocellular (primary abnormality is liver cell necrosis),
2. Cholestatic (primary abnormality is impairment of bile flow that may be
intrahepatic or extrahepatic).
• History and physical examination findings should be correlated with liver
function tests.
30.
HEPATOCELLULAR INJURY
1. Acute(e.g. acute viral hepatitis, toxic hepatitis, ischemic hepatitis,
alcoholic hepatitis)
2. Chronic (cirrhosis, chronic active hepatitis, autoimmune hepatitis).
• Acute hepatocellular injury is usually associated with marked elevation of
ALT and AST and mild elevation of alkaline phosphatase.
• Chronic hepatocellular injury, aminotransferases are moderately elevated,
and serum albumin is reduced.
31.
TYPICAL LFT PROFILEIN HEPATOCELLULAR DISEASE:
1. Marked elevation of AST and ALT (usually >500 IU)
2. Mild increase of ALP (<3 times normal)
3. Hyperbilirubinemia, if present, is of both conjugated and unconjugated
type
32.
CHOLESTASIS
1. Mild elevationof ALT and AST and marked increase of ALP and GGT.
• Typical LFT profile in cholestatic jaundice:
Marked elevation of ALP (>3 times normal),
Elevation of GGT and 5’-NT,
Mild or no increase of ALT and AST (usually <200 IU)
Elevation of conjugated bilirubin
34.
1. Severity ofliver disease is assessed by serum bilirubin, serum albumin, and
prothrombin time.
2. CHILD-TURCOTTE-PUGH classification is commonly used to assess severity
of cirrhosis and is based on both clinical and laboratory parameters.
35.
LIVER BIOPSY
• Procedurein which a small piece of liver tissue is removed and examined
microscopically to determine the cause and severity of liver disease.
• Paul Ehrlich performed the first percutaneous liver biopsy in 1883 in Germany.
Methods of obtaining liver biopsy are:
1. Percutaneous liver biopsy
2. Percutaneous ‘blind’ liver biopsy
3. Percutaneous guided liver biopsy
4. Percutaneous plugged liver biopsy
5. Transvenous (Transjugular) liver biopsy
6. Laparoscopic liver biopsy
37.
INDICATIONS
1. Acute hepatitisof unknown cause.
2. Chronic liver disease: To define cause, Grading of inflammatory activity, Staging
(prognosis) of chronic hepatitis C and chronic hepatitis B, Monitor response to
therapy.
3. Diagnosis of metabolic liver disorders like haemochromatosis and Wilson’s
disease.
4. Diagnosis and grading of alcoholic liver disease.
5. Accurate staging of advanced cases of primary biliary cirrhosis and primary
sclerosing cholangitis.
6. Investigation of persistently abnormal and unexplained LFTs.
7. Investigation of pyrexia of unknown origin.
8. Diagnosis of infections like tuberculosis.
9. Diagnosis of focal hepatic lesions
10. Histologic monitoring following liver transplantation.
38.
CONTRAINDICATIONS
1. Uncooperative patient
2.Extrahepatic biliary obstruction
3. Bleeding diathesis or abnormal coagulation profile
4. Tense ascites
5. Hydatid cyst of liver
6. Suspected hemangioma or other highly vascular tumor
7. Amyloidosis
8. Patients with encephalopathy, hepatic failure with severe jaundice, severe
congestive cardiac failure and advanced age are at increased risk of
complications following liver biopsy.
39.
Case 1
Test Testvalve Reference range
Total bilirubin 2.2 mg/dL 0.2-1.2 mg/dL
Direct bilirubin 0.4 mg/dL 0.2 mg/dL
Indirect bilirubin 1.8 mg/dL 0.2-1.0 mg/dL
Total albumin 3.0 grams/dL 3.5-5.0 grams/dL
SGOT 384 units/dL 7-55 units/dL
SGPT 110 units/dL 8-48 units/dL
ALP 140 units/dL 40-129 units/dL
PT/INR 1.56 0.8-1.1
Questions:
1. What is the most probable diagnosis
based on your interpretation?
2. Enumerate the light microscopic
findings of this condition.
3. Write the complication of this
condition.
A 45-year-old male presents with vague right hypochondrial pain, mild icterus and
confusion. His liver biopsy shows hepatic macrovesicular steatosis. His liver function
test shows the following findings.
Case 2
Test Testvalve Reference range
Total bilirubin 5.81 mg/dL 0.2-1.2 mg/dL
Direct bilirubin 4.37 mg/dL 0.2 mg/dL
Indirect bilirubin 1.44 mg/dL 0.2-1.0 mg/dL
Total albumin 3.4 grams/dL 3.5-5.0 grams/dL
SGOT 121 units/dL 7-55 units/dL
SGPT 98 units/dL 8-48 units/dL
ALP 260 units/dL 40-129 units/dL
PT/INR 1.0 0.8-1.1
Questions:
1. Which type of jaundice presents with
the finding mentioned above?
2. Write the different causes for this
condition.
3. What is the next line of investigation
that can be done for this patient?
60-year-old female presents with complaints of progressive jaundice, dark yellow urine
and clay-coloured stools. She also complains of vague dull aching pain in the right
hypochondrial region which worsens after fatty meals. Her liver function test shows the
following results.
Case 2
42.
CASE 2
ANSWERS:
1. Cholestaticjaundice / Obstructive jaundice / Post hepatic jaundice
2. Dubin-Johnson syndrome, Rotor syndrome, Cholelithiasis, Extrahepatic biliary
atresia, Adenocarcinoma of biliary tract.
3. Ultrasound, Liver biopsy
Case 2
43.
Case 3
Test Testvalve Reference range
Total bilirubin 4.8 mg/dL 0.2-1.2 mg/dL
Direct bilirubin 0.96 mg/dL 0.2 mg/dL
Indirect bilirubin 3.84 mg/dL 0.2-1.0 mg/dL
Total albumin 3.8 grams/dL 3.5-5.0 grams/dL
SGOT 61 units/dL 7-55 units/dL
SGPT 52 units/dL 8-48 units/dL
ALP 220 units/dL 40-129 units/dL
PT-INR 1.1 0.8-1.1
A 2-year-old male child presents with pallor, poor feeding and lethargy. On detailed history taking, the father
revealed that he required frequent blood transfusions during childhood and underwent splenectomy. On
examination, the child has icterus, moderate hepatosplenomegaly, heart rate (HR) was 110/min, respiratory
rate was 42/min. Peripheral blood smear examination showed features of spherocytosis. LDH levels are
raised. The liver function test shows the following results.
Questions:
1. What is your diagnosis?
2. Which additional test can be performed
to confirm your diagnosis?
3. Tabulate the difference between pre-
hepatic and post-hepatic jaundice.
Case 3
44.
CASE 3
PRE HEPATICJAUNDICE POST HEPATIC JAUNDICE
Unconjugated hyperbilirubinemia Conjugated hyperbilirubinemia
Excess bilirubin production or Defective
conjugation
Bile duct obstruction or injury
Cannot be excreted in urine Excreted in urine
Answers:
1. Hereditary spherocytosis
2. Osmatic fragility test
Case 3
45.
CASE 4:
• A26-year-old male who is an intravenous drug abuser comes with a history of flu-like
symptoms for the last 15 days. He has a mild fever with scleral icterus. On examination,
the abdomen is soft and non-tender, except the liver is tender when palpated and extends
8 cm below. A liver function test and viral serology were done.
Test Test valve Reference range
Total bilirubin 5.8 mg/dL 0.2-1.2 mg/dL
Direct bilirubin 1.8 mg/dL 0.2 mg/dL
Indirect bilirubin 4.0 mg/dL 0.2-1.0 mg/dL
Total albumin 3.4 grams/dL 3.5-5.0 grams/dL
SGOT 780 units/dL 7-55 units/dL
SGPT 672 units/dL 8-48 units/dL
ALP 176 units/dL 40-129 units/dL
PT/INR 1.5 0.8-1.1
Viral serology:
HBsAg – Positive,
HBc – Positive,
Anti HBc IgM – Negative
Questions:
1. What is the diagnosis based on your
interpretation?
2. Which virus is responsible for this condition?
3. Write about the different spectrums of
hepatitis caused by the virus.
Case 4