Liver Function in Clinical Pathology

Liver Function

• The liver is an organ with diverse metabolic activities, and assessing its functional status depends on its ability to perform specific metabolic functions.
• The liver has a tremendous functional reserve and powers of regeneration, making it challenging to estimate the presence or absence of hepatic malfunction.
• The various functions of the liver may be altered unequally by hepatic disease.

Indications for Liver Function Tests

• Assist in differential diagnosis of icterus resulting from hemolytic crisis or extrahepatic or intrahepatic obstruction of the bile duct system.
• Diagnose primary liver diseases with or without icterus, such as infectious hepatitis or suppurative hepatitis.
• Diagnose secondary liver disorders, such as chronic passive congestion, infiltrative and degenerative lipidoses.
• Evaluate prognosis of hepatic disease and therapy.

Limitations of Liver Function Tests

• Extensive damage is required before tests show impaired function due to the liver's great reserve power.
• Tests may lack sensitivity or be too sensitive.
• Testing one function does not indicate the function status of the entire organ.
• Specific hepatic functions are greatly affected by various pathologic conditions of extrahepatic origin.

Classification of Liver Function Tests

• Tests dependent on hepatic secretions and excretions:
  • Bile pigments
  • Clearance of foreign substances
• Tests dependent on specific biochemical functions:
  • Protein metabolism tests
  • Carbohydrate metabolism tests
  • Lipid metabolism tests
• Tests dependent on serum enzyme activity:
  • Transaminases
  • Alkaline phosphatase
  • Other enzymes

Bile Pigments

• Serum Bilirubin:
  • Chief bile pigment found in serum
  • Exists in two forms: protein-bound and conjugated (Bilirubin glucuronide)
  • Determination of total and conjugated bilirubin in serum is based on the van den Bergh reaction
  • Indications for serum bilirubin determination: classify icterus, measure response to therapy, and assist in making accurate prognosis
• Bile pigments in urine:
  • Urinary Urobilinogen: produced by bacterial reduction of bilirubin conjugates in the intestine
  • Fecal bilirubin: appears in conditions that prevent reduction of bilirubin to urobilinogen
  • Fecal bile pigments: normally present in feces, with stercobilin as the predominant pigment

Clearance of Foreign Dyes from the Serum

• Measure of biochemical integrity and blood flow in the liver
• Dyes used in veterinary medicine: Sulfobromophthalein (BSP), Rose Bengal, Indocyanine green (ICG), and Phenoltetrachlorophtalein
• Sulfobromophthalein: widely used index of hepatic function in domestic animals
• Indocyanine green: recommended for use in dogs to determine liver function

Tests Based on Specific Biochemical Functions

• Plasma proteins:
  • Include albumin, globulins, fibrinogen, glycoproteins, and lipoproteins
  • Indications for determining plasma proteins: estimate nutritional state, reflect alterations in metabolism, diagnose disease, and guide fluid administration in emergencies
• Protein metabolism tests:
  • Serum albumin and globulins
  • Coagulation factors
  • Amino acid tolerance test
  • Blood ammonia

Tests Based on Serum Enzyme Activity

• Alterations in serum enzyme activity due to liver malfunction:
  • Elevation of enzymes due to disruption of hepatic cells (ALT, AST, GD, LDH)
  • Decrease in enzyme levels due to impaired synthesis by the liver (Choline esterase)
  • Elevation in enzyme levels due to cholestasis (AP, GGT, LAP)
• Transaminases (Amino Transferases):
  • Alanine amino transferase (ALT)
  • Aspartate amino transferase (AST)
  • Indications for test: detect liver disease in dogs, cats, and primates

Liver Biopsy

• Procedure: insert a small needle into the liver to collect a tissue sample
• Indications:
  • Malignant hepatic neoplasms
  • Suspected fibrosis
  • Obscure liver disease
  • Metabolic diseases such as amyloidosis and lipidoses
  • Heavy metal intoxications by arsenic, molybdenum, or selenium