LIVER-lecture

• Liver


  Chief metabolic organ in the body
• Liver receives 15 mL of blood per minute
• Liver cells

  • Hepatocytes
  • Kupfer cells (phagocytic)
• Lobule


  Anatomic unit of liver
• Liver


  • Unique capacity to regenerate by cell division and hypertrophy of remaining tissue in case of tissue injury, biliary obstruction or toxic exposure
• Severe loss of hepatic functions may result in diagnostic changes in synthetic capacities, excretion, detoxification, and metabolic activity that are reflected in multiple standard and specialized tests
• To abolish liver tissue function, more than 80% of the liver must be destroyed
• Functions of the liver

  • Synthetic function
  • Conjugation function
  • Detoxification and drug metabolism
  • Excretory and secretory function
  • Storage function
• Synthetic function


  Liver secretes plasma proteins, carbohydrates, lipids, lipoproteins, clotting factors, ketone bodies, enzymes
• The normal liver produces about 12 grams of albumin daily
• Liver is involved in the metabolism of cholesterol into bile acids
• Conjugation function


  Liver is involved in the metabolism of bilirubin
• 200 to 300mg of bilirubin is produced daily in the healthy adult
• Detoxification and drug metabolism

  Liver serves to protect the body from potentially injurious substances absorbed from the intestinal tract and toxic by-products of metabolism
• Ammonia (toxic by-product) is converted to urea in the liver
• Excretory and secretory function

  Excretion of bile involves the elimination of bile acids or salts, pigments, cholesterol
• Bile acids (cholic acid and chenodeoxycholic acid) are conjugated with the amino acids glycine and taurine to form bile salts
• Storage function


  Storage site for all fat-soluble and water-soluble vitamins, storage depot for glycogen
• Serum albumin and vitamin K-dependent coagulation factors

  Most useful indices for assessing severity of liver disease
• Total protein


  Analysis is important for assessing nutritional status and presence of severe diseases involving the liver, kidney and bone marrow
• Total protein and albumin are about 10% higher in ambulatory individuals
• Plasma levels of total protein is 0.2 to 0.4 g/dL higher than serum due to fibrinogen
• Transudates


  Total protein of <3.0 g/dL (<50% of the serum total protein)
• Exudates


  Total protein of >3 g/dL
• Hemolysis and ictericia (jaundice) may falsely elevate the total protein (Biuret method)
• Reference value for total protein

  6.5-8.3 g/dL
• Kjeldahl method


  Reference method but not routinely used, based on measurement of the nitrogen content of protein
• According to Kjeldhal, 1 gram of nitrogen is equivalent to 6.54 grams of proteins
• Nitrogen content of proteins is 15.1%-16.8%
• Biuret method


  Most widely used method, recommended by the International Federation of Clinical Chemist (IFCC) Expert Panel, extensively used in clinical laboratories
• Biuret method


  Requires at least 2 peptide bonds and an alkaline medium to measure total protein, principle is cupric ions complex the groups involved in the peptide bond forming a violet-colored chelate
• Folin-Ciocalteu (Lowry) method


  Highest analytical sensitivity, principle is oxidation of phenolic compounds such as tyrosine, tryptophan, histidine to give a deep blue color
• Ultraviolet absorption method


  Principle is the absorbance of proteins at 210nm due to the absorbance of the peptide bonds, proteins also absorb light at 280nm due to tryptophan, tyrosine, phenylalanine
• Serum protein electrophoresis


  Principle is migration of charged particles in an electric field, most significant clinical application is for the identification of monoclonal spike of immunoglobulins and differentiating them from polyclonal hypergammaglobulinemia
• Major proteins that contribute to electrophoresis (MNEMONICS: FAAA BITCH)

  • Albumin
  • A1-antitrypsin
  • A2-macroglobulin
  • Haptoglobulin
  • B-lipoprotein
  • Transferrin
  • Complement C3
  • Fibrinogen
  • Immunoglobulins
• Alpha 1-globulin


  Glycoproteins, AAT, AAG, Thyroxine binding globulin (TBG), increases as a non-specific response to inflammation
• Alpha 2-globulin


  Haptoglobin, AMG, ceruloplasmin
• Beta-globulin


  Transferrin, beta-lipoprotein, hemopexin, complement (C3 and C4)
• Gamma-globulin


  Immunoglobulin and CRP
• Reference values for serum protein electrophoresis fractions

  • Albumin 53-65% (3.5-5.0 g/dL)
  • a1-globulin 2.5-5% (0.1-0.3 g/dL)
  • a2-globulin 7-13% (0.6-1.0 g/dL)
  • B-globulin 8-14% (0.7-1.1 g/dL)
  • Y-globulin 12-22% (0.8-1.6 g/dL)