more severe cases, actually dying (necrosis) and releasing their contents into the
surrounding extracellular fluid. In the vast majority of cases the extent of release of
specific cell components into the extracellular fluid, relative to the healthy reference
range, will reflect the extent of organ damage and this relationship forms the basis of
diagnostic clinical biochemistry. If the cause of the organ damage continues for a
prolonged time and is essentially irreversible (i.e. the organ does not undergo self-
repair), as is the case in cirrhosis of the liver for example, then the mass of cells
remaining to undergo necrosis will progressively decline so that eventually the release
of cell components into the surrounding extracellular fluid will decrease even though
organ cells are continuing to be damaged. In such case the measured amounts will not
reflect the extent of organ damage.
Clinical biochemical tests have been developed to complement in four main ways
a provisional clinical diagnosis based on the patient’s medical history and clinical
examination:- To support or reject a provisional diagnosisby detecting and quantifying abnormal
amounts of test analytes consistent with the diagnosis. For example, serum myoglobin,
troponin-I (part of the cardiac contractile muscle), creatine phosphokinase (specifically
the CK-MB isoform) and aspartate transaminase all rise following a myocardial infarction
(heart attack) that results in cell death in some heart tissue. The released cellular
components also cause cell inflammation (leakiness) in surrounding cells causing an
amplification of total cellular component release. Tests can also help a differential
diagnosis, for example in distinguishing the various forms of jaundice (yellowing of the
skin due to the presence of the yellow pigment bilirubin, a metabolite of haem) by the
measurement of alanine transaminase (ALT) and aspartate transaminase (AST) activities
and by determining whether or not the bilirubin is conjugated withb-glucuronic acid. - To monitor recovery following treatmentby repeating the tests on a regular basis and
monitoring the return of the test values to those within the reference range. Following
a myocardial infarction,for example,the raised serumenzyme activitiesreferredto above
usually return to reference range values within 10 days (Section 16.3.2, Fig. 16.3).
Similarly, the measurement of serum tumour markers such as CA125 can be used to
follow recovery or recurrence after treatment for ovarian cancer. - To screen for latent diseasein apparently healthy individuals by testing for raised levels
of key analytes. For example, measuring serum glucose for diabetes mellitus and
immunoreactive trypsin for cystic fibrosis. It is now common for serum cholesterol
levels to be used as a measure of the risk of the individual developing heart disease.
This is particularly important for individuals with a family history of the disease. An
action limit of serum cholesterol>5.2 mM has been set by the British Hyperlipidaemia
Association for an individual to be counselled on the importance of a healthy (low
fat) diet and regular exercise and a higher action limit of serum cholesterol>6.6 mM
for cholesterol-lowering ‘statin’ drugs to be prescribed (Section 18.2.2) and clinical
advice given. - To detect toxic side effects of treatment, for example in patients receiving hepatotoxic
drugs, by undertaking regular liver function tests. An extension of this istherapeutic
drug monitoringin which patients receiving drugs such as phenytoin and
627 16.1 Principles of clinical biochemical analysis