Principles of Clinical Biochemistry | Examples of Biochemical Aids to Clinical Diagnosis
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Principles of Clinical Biochemistry | Examples of Biochemical Aids to Clinical Diagnosis
Diagnostic enzymology is routinely used to discriminate between several forms of liver disease, including:
• Hepatitis : General inflammation of the liver most commonly caused by viral infection, but which may also be a consequence of blood poisoning (septicaemia) or glandular fever. Acute hepatitis can show a marked increase (60-fold) in aminotransferases over a few days before returning to normal.
• Cirrhosis: A general destruction of the liver cells and their replacement by fibrous tissue. It is most commonly caused by excess alcohol intake, but is also a result of prolonged hepatitis, various autoimmune diseases and genetic conditions. Enzyme activity may only be mildly elevated when chronic liver damage is present.
• Malignancy: Primary and Secondary tumours.
• Cholestasis: The prevention of bile from reaching the gut either due to blockage of the bile duct by gallstones or tumours, or to liver cell destruction as a result of cirrhosis or prolonged hepatitis. This gives rise to obstructive jaundice (presence of bilirubin, a yellow metabolite of haem, in the skin).
• Obesity: Serum aminotransferases can be mildly but persistently elevated in obese subjects reflecting non-alcoholic fatty liver disease.
Patients with these various liver diseases often present to their doctor with similar symptoms and a differential diagnosis needs to be made on the basis of a range of investigations, including imaging techniques, especially ultrasonography (ultrasound), magnetic resonance imaging (MRI), computerised tomography (CT) scanning, microscopic examination of biopsy samples and liver function tests. Following enzymes are routinely assayed to aid differential diagnosis:
Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): As previously stated, these enzymes are widely distributed, but their ratios in serum are characteristic of the specific cause of liver cell damage.
AST / ALT Ratio is important
for example,
a ratio of less than 1 is found in non-alcoholic fatty liver disease, ( <1 )
a ratio of about 1 in obstructive jaundice caused by viral hepatitis and ( =1 )
a ratio of greater than 1 in alcohol abuse. ( >1 )
Aspartate aminotransferase activity: This is assessed by a coupled assay with malate dehydrogenase and the measurement of the decrease in absorbance at 340 nm:
Alanine aminotransferase activity : This is also assessed by a coupled assay, in this case with lactate dehydrogenase and the measurement of the decrease in absorbance at 340 nm:
Source:
Wilson and Walker's Principles and Techniques of Biochemistry and Molecular Biology, Eighth Edition