LIVER FUNCTION TESTS
Liver is composed of three system
✓The hepatocytes – concerned with metabolic reactions, macromolecular
synthesis and degradation and metabolism of xenobiotics
✓The biliary system – metabolism of bilirubin and bile salts,
✓The reticuloendothelial system – concerned with immune system and
production of heme and globin metabolites
FUNCTIONS OF LIVER
•Storage of Glycogen, Iron and vitamins
•Deamination and transamination of amino acids
•Ammonia detoxification
•Fetal life - hematopoiesis occurs in the liver and immune hemolysis
•Catabolism of steroid hormones
LFT – INDICATIONS
•Screen for liver disease
•Identify nature of liver disease (hepatocellular, cholestatic, or infiltrative)
•Assess severity and prognosis of liver disease
•Follow up course of liver disease
LFT – LIMITATIONS
•Lack sensitivity (i.e. may be normal in some liver diseases like cirrhosis)
•Lack specificity (i.e. may be abnormal in non-liver disorders e.g. serum
albumin is low in nephrotic syndrome)
BILIRUBIN METABOLISM
Differential Diagnosis Based on Elevated LFTs
Hepatocellular pattern: Elevated aminotransferases out of proportion
to alkaline phosphatase
Cholestatic pattern: Elevated alkaline phosphatase +gamma glutamyl
transferase + bilirubin out of proportion to AST and ALT
PARAMETERS
SERUM BILURUBIN
Total serum bilirubin - Normal <1.2 mg/dl
Pre-hepatic/ unconjugated/ indirect – 0.2 – 0.9 mg/dl
Post-hepatic/ conjugated/ direct – 0.1 – 0.3 mg/dl
SYNTHETIC AND METABOLIC
FUNCTIONS OF LIVER
•Proteins –
✓Total serum protein ( 6- 8 g/dl)
✓Sr Albumin (3.50-5.20 g/dl)
✓Sr Globulin (1.80-3.40 g/dl)
✓A/G ratio (normal ratio is >1.5)
•Prothrombin time (PT) (11-16 sec)
SERUM ALBUMIN
✓60% of total proteins in serum
✓Determines synthetic capacity of hepatocytes
✓Half life-20 days
✓Acute liver disease (viral hepatitis)- little change
✓Chronic liver disease (cirrhosis)- decrease(marker of chronicity-low)
ALBUMIN GLOBULIN RATIO
Formula : albumin level
(Total protein- Albumin level)
Normal value : 1.5- 1.80
PROTHROMBIN TIME (PT)
Vitamin K dependent factors - II, VII, IX, and X
In hepatocellular disease-Deficient Synthesis of these factors
Obstructive jaundice - vitamin K (fat-soluble) not absorbed due to the absence of
bile in the intestine.
Prolonged PT - hepatocellular disease and obstructive jaundice.
BLOOD AMMONIA
GIT portal vein liver
Ammonia to nontoxic urea(urea cycle)
↑ Blood Ammonia levels -
Fulminant hepatic failure
Cirrhosis
Reye’s syndrome
“Shunting” of portal blood to systemic circulation
Gastrointestinal hemorrhage
inherited deficiencies of urea cycle enzymes
LIVER ENZYME STUDIES
•Serum aspartate aminotransferase or
AST (SGOT)
•Serum alanine aminotransferase or ALT
(SGPT)
•Serum alkaline phosphatase or ALP
•γ-Glutamyl transferase or GGT
ALT/AST
AST – Liver > cardiac muscle > skeletal muscle > kidneys > brain
ALT– specifically liver
Both normal – 0 – 30 IU/L
Hepatocellular injury → ↑ membrane permeability → ↑ Serum levels
AST is rapidly cleared by reticuloendothelial system ALT>AST always
HEPATIC CAUSES OF MARKEDLY ELEVATED
ALT/AST (>1000 IU/L)
AST/ALT RATIO- ALCOHOLIC
LIVER DISEASE
Normal – 0.7 – 1.4
2:1 → Suggestive of ALD
3:1 → Highly suggestive of ALD
ALP- ALKALINE PHOSPHATASE
Normal – 40-120 IU/L
ALP – Liver > bone > placenta > small intestine
Considered significant – if elevated 4 times normal
Physiological increase (upper limit -never 4 times )
Pregnancy
>60 years of age
After a fatty meal
Children and adolescents
ALP – MARKED ELEVATION
(>4X)
Cholestasis
Infiltrative liver disease (eg: cancer,
amyloidosis)
Paget’s disease of bone
ALT-predominant:
Acute or chronic viral hepatitis, steatohepatitis, acute Budd-Chiari syndrome,
ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins,
autoimmune, alpha1-antitrypsin deficiency, Wilson disease, Celiac disease
AST-predominant:
Alcohol-related, cirrhosis, non-hepatic (hemolysis, myopathy, thyroid
disease, exercise)
SERUM GGT
Normal GGT (liver)– 10 – 47 IU/L
Elevated
Cholestasis (more specific is GGT )
ALD
Acute hepatitis – recovery phase
LFTS PROFILES IN COMMON LIVER DISEASES
Disorder Bilirubin AST/ALT ALP Albumin PT
Hemolysis/ N/ Normal Normal Normal Normal
Gilbert unconjugated
Acute Both Elevated N/ <3 times N Normal Usually
hepatocellular elevated; ALT/AST Normal
disease bilirubinuria +
Chronic Both Elevated N/<3 times N Decrease Prolonged
hepatocellular elevated; <300 u/l
disease Bilirubinuria +
LFTS PROFILES IN COMMON LIVER DISEASES
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