liver_function_tests otgan function lft lft (2).ppt
1. Explain the rationale and basis and
interpretation of biochemical tests
done in Liver diseases
2. Major Metabolic Functions of the Liver
• Synthetic Function
▫ Plasma proteins (albumin, globulins), cholesterol, triglycerides
and lipoproteins
• Detoxification and excretion
▫ Ammonia to urea (urea cycle), bilirubin, cholesterol, drug
metabolites
• Storage Function
▫ Vitamins A, D, E, K and B12
• Production of bile salts
▫ Helps in digestion
▫ Along with glucose homeostatsis and metabolic functions
3. Clinical Manifestation of liver disease
1. Jaundice- Bile pigment deposition on skin, sclera,
excretion in urine
2. Bleeding
3. Ascites- Deposition of Fluid in abdominal cavity
4. Fat Malabsorption
20. Some example of liver dysfunction
• Hepatocellular disease
• Cholestasis (obstruction of bile flow)
• Cirrhosis
• Hepatitis
• Jaundice
• Liver cancer
• Steatosis (fatty liver)
• Genetic Disorders
▫ Hemochromatosis (iron storage)
▫ Glycogen storage diseases
21. Clinical Manifestation of liver disease
1. Jaundice- Bile pigment deposition on skin, sclera,
excreation in urine.
2. Bleeding
3. Ascitis- Deposition of Fluid in abdominal cavity
4. Fat Malabsorption
23. Liver Function Tests (LFTs)
• Noninvasive methods for screening of liver
dysfunction
• Help in identifying general types of disorder
• Assess severity and allow prediction of outcome
• Disease and treatment follow up
24. Classification based on laboratory
findings
• Group I (tests of hepatic excretory
function)
Substances detoxified by the liver are excreted through bile
i. Serum—bilirubin; total, conjugated and unconjugated
ii. Urine—bile pigments, bile salts and urobilinogen
26. Group III: Plasma proteins (Tests
for synthetic function of liver)
• Total proteins
• Serum albumin, globulins, A/G ratio
• Prothrombin time
• Blood ammonia
27. Group IV: Special tests
• Ceruloplasmin
• Ferritin
• Alpha-1-antitrypsin (AAT)
• Beta-2 microglobulin (b2M)
• Alpha fetoprotein (AFP)
28. Group V: Direct and indirect
markers of hepatic fibrosis
• Serum hyaluronic acid (SHA)
• Procollagen type I carboxy terminal peptide
• Procollagen type III amino terminal peptide
29. Group I: Markers of liver dysfunction
▫ Serum bilirubin: total and conjugated
▫ Urine: bile salts and urobilinogen
▫ Total protein, serum albumin and albumin/globulin
ratio
▫ Prothrombin Time
▫ Blood Ammonia
Classification based on clinical
aspects:
30. Classification based on clinical
aspects:
Group II: Markers of hepatocellular injury
▫ Alanine aminotransferase (ALT)
▫ Aspartate aminotransferase (AST)
31. Group III: Markers of cholestasis
▫ Alkaline phosphatase (ALP)
▫ g-glutamyltransferase (GGT)
32. Bilirubin
• A byproduct of heme catabolism
• It is the yellowish pigment observed in jaundice
39. Urobilinogen, Bile salts & Bile pigments
• Most UBG is metabolized in the large intestine but a
fraction is excreted in urine (less than 4 mg/day)
• Normally bile salts are NOT present in urine
• Obstruction in the biliary passages causes:
▫ Leakage of bile salts into circulation
▫ Excretion in urine
42. Hemoly
tic
jaundic
e
Obstructiv
e
jaundice
Hepatocellular
jaundice
Bile
pigments
Absent +++ ++
Bile salts Absent ++ +
Urobilinoge
n
Elevated Absent Normal or
decreased
Positive test Ehrlich’s
+ve
Fouchet’s
+ve
Hey’s +ve
Laboratory Findings in Urine in Jaundice Cases
Hemoly
tic
jaundic
e
Obstructiv
e
jaundice
Hepatocellular
jaundice
Bile
pigments
Absent +++ ++
Bile salts Absent ++ +
Urobilinoge
n
Elevated Absent Normal or
decreased
Positive test Ehrlich’s
+ve
Fouchet’s
+ve
Hay’s +ve
43. Serum Albumin
• The most abundant protein synthesized by the liver
• Normal serum levels: 3.5 – 5 g/dL
• Synthesis depends on the extent of functioning liver
cell mass
• Longer half-life: 20 days
• Its levels decrease in all chronic liver diseases
44. Serum Globulin
• Normal serum levels: 2.5 – 3.5g/dL
• alpha and beta-globulins mainly synthesized by the
liver
• They constitute immunoglobulins (antibodies)
• High serum g-globulins are observed in chronic
hepatitis and cirrhosis:
▫ IgG in autoimmune hepatitis
▫ IgA in alcoholic liver disease
45. Albumin to globulin (A/G) ratio
• Normal A/G ratio: 1.2/1 – 1.5/1
• Globulin levels increase in hypoalbuminemia as a
compensation
47. Aspartate aminotransferase (AST)
• Normal range: 5 – 35 U/L
• A marker of hepatocellular damage
• High serum levels are observed in:
▫ Chronic hepatitis, cirrhosis and liver cancer
Oxaloacetate + Glutamate Aspartate +α Ketoglutarate
AST/
SGOT
48. Alanine aminotransferase (ALT)
• More liver-specific than AST
• Normal range (U/L): 5-35 IU/L
• High serum levels in acute hepatitis (300-1000IU/L)
• Moderate elevation in alcoholic hepatitis (100-
300IU/L)
• Minor elevation in cirrhosis, hepatitis C and non-
alcoholic steatohepatitis (NASH) (50-100IU/L)
49. Alanine aminotransferase (ALT)
• Appears in plasma many days before clinical signs
appear
• A normal value does not always indicate absence of liver
damage
• Obese but otherwise normal individuals may have
elevated ALT levels
Pyruvate +Glutamate Alanine+ α Ketoglutrate
ALT/
SGPT
50. • Both enzymes are present in cytosol of the liver
cells.
• AST is also present in mit.
• When cells break, enzymes leak in blood.
• In early ds ALT is higher in blood than AST
51. Alkaline phosphatase (ALP)
• A non-specific marker of liver disease
• Produced by bone osteoblasts (for bone calcification)
• Present on hepatocyte membrane
52. Alkaline phosphatase (ALP)
• Hepatobilliary disease induces enzyme synthesis enter
in circulation
• Moderate elevation observed in:
▫ Infective hepatitis, alcoholic hepatitis and
hepatocellular carcinoma
54. Gama-glutamyltransferase (GGT)
• Used for glutathione synthesis
• Normal range: 2 – 30U/L
• Moderate elevation observed in:
▫ Infective hepatitis and prostate cancers
• GGT is increased in alcoholics despite normal liver
function tests
▫ Highly sensitive to detecting alcohol abuse
55. • A/a + Glutathione g-glutamyl A/a+ Cyst- Gly
• Present in endoplasmic reticulum of hepatocytes
g- GGT
(Glu- Gly-Cys)
