The interpretation of results

Published on 01/03/2015 by admin

Last modified 22/04/2025

Print this page

This article have been viewed 1089 times

The interpretation of results

It can take considerable effort, and expense, to produce what may seem to be just numbers on pieces of paper or on a computer screen. Understanding what these numbers mean is of crucial importance if the correct diagnosis is to be made, or if the patient’s treatment is to be changed.

How biochemical results are expressed

Most biochemical analyses are quantitative, although simple qualitative or semi-quantitative tests, such as those for the presence of glucose in urine, are commonly encountered methods used for point of care testing. Many tests measure the amount of the analyte in a small volume of blood, plasma, serum, urine or some other fluid or tissue. Results are reported as concentrations, usually in terms of the number of moles in one litre (mol/L) (Table 3.1).

Table 3.1

Molar units

Mole	Abbreviation	Definition
Millimole	mmol	×10⁻³ of a mole
Micromole	µmol	×10⁻⁶
Nanomole	nmol	×10⁻⁹
Picomole	pmol	×10⁻¹²
Femtomole	fmol	×10⁻¹⁵

The concept of concentration is illustrated in Figure 3.1. The concentration of any analyte in a body compartment is a ratio: the amount of the substance dissolved in a known volume. Changes in concentration can occur for two reasons:

Fig 3.1 Understanding concentrations. Concentration is always dependent on two factors: the amount of solute and the amount of solvent. The concentration of the sugar solution in the beaker can be increased from 1 spoon/beaker (a) to 2 spoons/beaker by either decreasing the volume of solvent (b) or increasing the amount of solute (c).

The amount of the analyte can increase or decrease.

The volume of fluid in which the analyte is dissolved can similarly change.

Enzymes are not usually expressed in moles but as enzyme activity in ‘units’. Enzyme assays are carried out in such a way that the activity measured is directly proportional to the amount of enzyme present. Some hormone measurements are expressed as ‘units’ by comparison to standard reference preparations of known biological potency. Large molecules such as proteins are reported in mass units (grams or milligrams) per litre. Blood gas results (PCO₂ or PO₂) are expressed in kilopascals (kPa), the unit in which partial pressures are measured.

Variation in results

Biochemical measurements vary for two reasons. These are described as ‘analytical variation’ and ‘biological variation’. Analytical variation is a function of analytical performance; biological variation is related to the actual changes that take place in patients’ body fluids over a period of time.

Laboratory analytical performance

A number of terms describe biochemical results. These include:

precision and accuracy

sensitivity and specificity

quality assurance

reference intervals.

Precision and accuracy

Precision is the reproducibility of an analytical method. Accuracy defines how close the measured value is to the actual value. A good analogy is that of the shooting target. Figure 3.2 shows the scatter of results which might be obtained by someone with little skill, compared with that of someone with good precision where the results are closely grouped together. Even when the results are all close, they may not hit the centre of the target. Accuracy is therefore poor, as if the ‘sights’ are off. It is the objective in every biochemical method to provide good precision and accuracy. Automation of analyses has improved precision in most cases.

Fig 3.2 Precision and accuracy.

Analytical sensitivity and specificity

The analytical sensitivity of an assay is a measure of how little of the analyte the method can detect. Analytical specificity of an assay relates to how good the assay is at discriminating between the requested analyte and potentially interfering substances. These terms describing the analytical properties of tests should not be confused with ‘test’ specificity and sensitivity, as applied to the usefulness of various analyses (see below).

Quality assurance

Laboratory staff monitor performance of assays using quality control samples to give reassurance that the method is performing satisfactorily with the patients’ specimens. Internal quality control samples are analysed regularly. The expected values are known and the actual results obtained are compared with previous values to monitor performance. In external quality assurance programmes, identical samples are distributed to laboratories; results are then compared.

Reference intervals

Analytical variation is generally less than that from biological variation. Biochemical test results are usually compared to a reference interval chosen arbitrarily to include 95% of the values found in healthy volunteers (Fig 3.3). This means that, by definition, 5% of any population will have a result outside the reference interval. In practice there are no rigid limits demarcating the diseased population from the healthy; however, the further a result is from the limits of the reference interval, the more likely it is to indicate pathology. In some situations it is useful to define ‘action limits’, at which appropriate intervention should be made in response to a biochemical result. An example of this is plasma cholesterol.

Fig 3.3 (a) Overlap of biochemical results in health and disease. (b) and (c) The effect of changing the diagnostic cut-off on test specificity and sensitivity.

There is often a degree of overlap between the disease state and the ‘normal value’ (Fig 3.3). An abnormal result in a patient who is subsequently found not to have the disease is called a ‘false positive’. A ‘normal result’ in a patient who has the disease is a ‘false negative’.