The concentration, amount or activity of a given cell component that can be detected
in these fluids of a healthy individual at any point in time depends on many factors that
can be classified into one of three categories, namely chemical characteristics of the
component, endogenous factors characteristic of the individual and exogenous factors
that are imposed on the individual.- Chemical characteristics: Some molecules are inherently unstable outside their normal
cellular environment. For example, some enzymes are reliant on the presence of their
substrate and/or coenzyme for their stability and these may be absent or in too low
concentrations in the extracellular fluid. Molecules that can act as substrates of catabolic
enzymes found in extracellular fluids, in particular blood, will also be quickly metabolised.
Cell components that fall into these two categories therefore have a shorthalf-life outside
the cell and are normally present in low concentrations in fluids such as blood. - Endogenous factors: These include age, gender, body mass and pregnancy. For example:
(a) serum cholesterol concentrations are higher in men than premenopausal women
but the differences decreases post-menopause;
(b) serum alkaline phosphatase activity is higher in children than in adults
and is raised in women during pregnancy;
(c) serum insulin and triglyceride concentrations are higher in obese individuals
than in the lean;
(d) serum creatinine, a metabolic product of creatine important in muscle
metabolism, is higher in individuals with a large muscle mass;
(e) serum sex hormone concentrations differ between males and females and change
with age. - Exogenous factors: These include time, exercise, food intake and stress. Several hormones
are secreted in a time-related fashion. Thus cortisol and to a lesser extent thyroid
stimulating hormone (TSH) and prolactin all show a diurnal rhythm in their secretion.
In the case of cortisol, its secretion peaks around 9.00 am and declines during the day
reaching a trough between 11.00 pm and 5.00 am. The secretion of female sex hormones
varies during a menstrual cycle and that of 25-hydroxycholecalciferol (vitamin D 3 )
varies with the seasons peaking during the late summer months. The concentrations
of glucose, triglycerides andinsulin in blood rise shortly after the intake of a meal.
Stress, including that imposed by the process of taking a blood sample by puncturing
avein(venipuncture), can stimulate the secretion of a number of hormones and
neurotransmitters including prolactin, cortisol, adrenocorticotropic hormone (ACTH)
and adrenaline.
The influence of these various factors on the extent of release of cell components
into extracellular fluids inevitably means that even in healthy individuals there is a
considerableintraindividual variation(i.e. variation from one occasion to another) in
the value of any chosen test analyte of diagnostic importance and an even larger
interindividual variation(i.e. variation between individuals). More importantly, the
superimposition of a disease state onto these causes of intra- and interindividual
variation will result in an even greater variability between test occasions.
Many clinical conditions compromise the integrity of cells located in the organs
affected by the condition. This may result in the cells becoming more ‘leaky’ or, in626 Principles of clinical biochemistry