serum increases at the same rate as CK-MB after a myocardial infarction, has a similar
time for 100% sensitivity and for peak time, but it remains raised for up to 4 days after
the onset of symptoms. Its reference range is less than 1 ng cm^3 but its concentration
in serum is raised to up to 30–50 ng cm^3 within 24 hours of a myocardial infarction
event. It is assayed by a ‘sandwich’ immunological assay in which the antibody is
labelled with alkaline phosphatase. Using 4-methylumbelliferone phosphate as
substrate, the release of 4-methylumbelliferone is measured by fluorescence. The
measurement of serum troponin-I is widely used to exclude cardiac damage in
patients with chest pain since it remains raised for several days following a
myocardial infarction, but the timing of the test sample is important as a sample taken
too early may give a false negative result. A limitation of its use is that its release into
serum is not specific to myocardial infarction; an increase in serum mass may occur
following a crush injury.
The measurement of enzyme activities and myoglobin and troponin-I concentra-
tions, together with plasma potassium, glucose and arterial blood gases, is routinely
used to monitor the recovery of patients following a myocardial infarction. A patient
may experience a second myocardial infarction within a few days of the first. In such
cases the pattern of serum enzymes shown in Fig. 16.4 is repeated, the pattern being
superimposed on the remnants of the first profile. CK-MB is the best initial indicator of
a second infarction since the levels of troponin-I may not reflect a secondary event.
The sensitivity and specificity (Section 16.1.2) of ECG and diagnostic enzymology
in the management of heart disease are complementary. Thus the specificity of ECG is
100% whilst that of enzyme measurements is 90%, and the sensitivity of ECG is 70%
whilst that of enzyme measurements is 95%.16.3.3 Liver disease
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. It results in only mild necrosis of the hepatic cells and hence of a modest release
of cellular enzymes. - 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. They all
result in extensive cell damage and release of hepatic cell enzymes. - Malignancy: Primary and secondary tumours.
- Cholestasis: The prevention of bile from reaching the gut due either 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 toobstructive jaundice(presence of bilirubin,
a yellow metabolite of haem, in the skin).
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 of645 16.3 Examples of biochemical aids to clinical diagnosis