Page 611 - Textbook of Pathology, 6th Edition

II. SERUM ENZYME ASSAYS i) 5'-Nucleotidase is another phosphatase derived from the 595
liver. Its determination is useful to distinguish alkaline
Determination of certain serum enzymes is considered useful phosphatase of hepatic origin from that of bony tissue.
in various types of liver injury, whether hepatocellular or
cholestatic, as well as in quantifying liver damage. A ii) Lactic dehydrogenase (LDH) is found to be elevated in
combination of serum transaminases and alkaline serum of patients with metastatic liver involvement.
phosphatase estimation is adequate to diagnose liver injury. iii) Choline esterase synthesised by the liver is diminished in
hepatocellular disease and malnutrition due to impaired
1. ALKALINE PHOSPHATASE. Serum alkaline phos- synthesis.
phatase is produced by many tissues, especially bone, liver,
intestine and placenta and is excreted in the bile. Most of the III. TESTS FOR METABOLIC FUNCTIONS
normal serum alkaline phosphatase (range 33-96 U/L) is
derived from bone. Elevation in activity of the enzyme can The liver is the principal site of metabolism and synthesis of
thus be found in diseases of bone, liver and in pregnancy. In plasma proteins and amino acids, lipids and lipoproteins,
the absence of bone disease and pregnancy, an elevated carbohydrates and vitamins, besides detoxification of drugs
serum alkaline phosphatase levels generally reflect and alcohol.
hepatobiliary disease. The greatest elevation (3 to 10 times 1. AMINO ACID AND PLASMA PROTEIN META-
normal) occurs in biliary tract obstruction. Slight to moderate BOLISM. Amino acids derived from the diet and from
increase is seen in parenchymal liver diseases such as in tissue breakdown are metabolised in the liver to ammonia
hepatitis and cirrhosis and in metastatic liver disease. It is and urea. A number of plasma proteins and immuno-
possible to distinguish serum hepatic alkaline phosphatase globulins are synthesised on polyribosomes bound to the
from bony alkaline phosphatase by fractionation into rough endoplasmic reticulum within the hepatocytes and
isoenzymes but this is not routinely done. discharged into plasma. Based on these metabolic functions
2. γγ γγ γ-GLUTAMYL TRANSPEPTIDASE (γγ γ γ γ-GT). The of the liver, serum estimation of proteins, immunoglobulins
primary source of the enzyme, γ-GT, in serum is the liver. and ammonia and aminoaciduria are employed to assess
Its serum level parallels serum alkaline phosphatase and is the liver cell damage.
used to confirm that the elevated serum alkaline phosphatase i) Serum proteins. Liver cells synthesise albumin, CHAPTER 21
is of hepatobiliary origin. Besides its elevation in cholestasis fibrinogen, prothrombin, alpha-1-antitrypsin, haptoglobin,
and hepatocellular disease, the levels are high in patients ceruloplasmin, transferrin, alpha fetoproteins and acute
with alcohol abuse even without liver disease. phase reactant proteins. The blood levels of these plasma
proteins are decreased in extensive liver damage. Routinely
3. TRANSAMINASES (AMINOTRANSFERASES). estimated are total concentration of serum proteins (normal
Assessment of liver cell necrosis is most frequently done by 6.7 to 8.6 gm/dl), serum albumin (normal 3.5 to 5.5 gm/dl),
estimation of the following 2 serum enzymes:
serum globulin (normal 2 to 3.5 gm/dl) and albumin/
i) Serum aspartate transaminase or AST (formerly globulin (A/G) ratio (normal 1.5-3:1). Electrophoresis is used
glutamic oxaloacetic transaminase or SGOT): AST or SGOT to determine the proportions of α , α , β and γ globulins.
2
1
is a mitochondrial enzyme released from heart, liver, skeletal Due to the availability of protein electrophoresis, thymol
muscle and kidney. Its normal serum level is 0.20-0.65 turbidity and flocculation tests based on altered plasma
μkat/L (12-38 U/L). protein components have been discontinued.
ii) Serum alanine transaminase or ALT (formerly glutamic Hypoalbuminaemia may occur in liver diseases having
pyruvic transaminase or SGPT): ALT or SGPT is a cytosolic significant destruction of hepatocytes. Hyperglobulinaemia
enzyme primarily present in the liver. Its normal serum level may be present in chronic inflammatory disorders such as The Liver, Biliary Tract and Exocrine Pancreas
is 0.12-0.70 μkat/L (7-41 U/L). in cirrhosis and chronic hepatitis.
Serum levels of SGOT and SGPT are increased on damage ii) Immunoglobulins. The levels of serum immuno-
to the tissues producing them. Thus serum estimation of globulins produced by lymphocytes and plasma cells (IgG,
SGPT (ALT) which is fairly specific for liver tissue is of IgM and IgA) show nonspecific abnormalities in liver
greater value in liver cell injury, whereas SGOT (AST) level diseases and represent inflammatory or immune response
may rise in acute necrosis or ischaemia of other organs such rather than liver cell dysfunction. IgA is the predominant
as the myocardium, besides liver cell injury. immunoglobulin in bile and its level is raised in cirrhosis,
Transaminase estimations are useful in the early IgG is markedly raised in chronic active hepatitis and IgM
diagnosis of viral hepatitis. Very high levels are seen in is markedly increased in primary biliary cirrhosis.
extensive acute hepatic necrosis such as in severe viral iii) Clotting factors. Hepatic synthetic function of several
hepatitis and acute cholestasis. Alcoholic liver disease and clotting factors can be assessed by a few simple coagulation
cirrhosis are associated with mild to moderate elevation of tests. Prothrombin time and partial thromboplastin time,
transaminases.
both of which reflect the activities of various clotting factors,
4. OTHER SERUM ENZYMES. The determination of a few are prolonged in patients with hepatocellular disease.
other serum enzymes is done sometimes but without any Prothrombin time is dependent upon both hepatic synthesis
extra diagnostic advantage over the above mentioned of clotting factors and intestinal uptake of vitamin K, a fat-
enzyme assays. These are as under: soluble vitamin. Thus, obstruction of the bile duct and intra-