Physiological variables

The normal range should be established with samples obtained from an adequate sample of healthy persons of specified age and sex. The effect of physiological variables such as activity, eating, menstruation and pregnancy should be known. The confidence limits should be determined with the appropriate statistical tools. Normal ranges determined with hospital patients should be rejected (20 21). 

Some physiological variables influence the measurement of fibrinolytic activators and inhibitors. For instance, both t-PA and plasminogen activator inhibitor 1 (PAI-1) levels in plasma are subject to diurnal variation in a 12-hour period. Even in samples taken at the same time of day the coefficient of variation (CV) of measured PAI levels range from 8 to 143% To account for this diurnal variation, blood samples spaced over several time intervals during a 24-hour period should be collected. Consumption of alcohol induces the PAI level in plasma. The half-life of t-PA is 360 seconds. However, in the presence of trauma or inflammation, when the PAI-1 level is expected to be elevated 10-fold, the half-life of t-PA is reduced to 36 seconds (114). 

Many different types of sensory receptors are located throughout the body. These receptors monitor the status of the internal environment or that of the surroundings. Sensory receptors are sensitive to specific types of stimuli and measure the value of a physiological variable. For example, arterial baroreceptors measure blood pressure and chemoreceptors measure the oxygen and carbon dioxide content of the blood. The information detected by these sensors then travels by way of afferent neuronal pathways to the central nervous system (CNS). The CNS is the integrative portion of the nervous system and consists of the (1) brain and the (2) spinal cord. 

The most important physiological variable determining the resistance to blood flow is vessel radius. A given volume of blood comes into less contact with the wall of a vessel with a large radius compared to a vessel with a small radius. Therefore, as the radius of a vessel increases, the resistance to blood flow decreases. In other words, blood flows more readily through a larger vessel than it does through a smaller vessel. 

Body iron content is the principal factor in the regulation of iron absorption (Marx,1979a,b). However, other physiological variables, such as erythropoietic rate (Bothwell, 1968), hypoxia (Raja et ah, 1988) and inflammation (Weber et ah, 1988) also influence iron absorption. In normal individuals, if the rate of erythropoiesis is stimulated by blood loss, dyserythropoiesis or acute haemolysis, iron absorption is increased. Conversely, if erythropoiesis is inhibited by hypertransfusion, starvation or descent from high altitude to sea level, then iron absorption decreases. The adaptive response of iron absorption to increased erythropoiesis, stimulated... 

The QT interval is a dynamic physiological variable depending on multiple factors such as cardiac cycle length (heart rate), autonomic nervous system activity, age, gender, plasma electrolyte concentrations, genetic variations in ion channels involved in cardiac repolarization. In addition, circadian and seasonal variations of the QT interval have been described [93]. 

Medical devices, in general, are human-made structures or machines that function inside or outside the body and have a role in human functioning either in sensing or manipulating a physiological variable. If they are implanted in a host, they may be a temporary or a permanent device. 

Concentrations of Na", C, and Cl in body fluids, and the physiological variables dependent on these (e. g. blood pressure), are subject to strict regulation. The principal site of action of the hormones involved is the kidneys, where hormones increase or reduce the resorption of ions and recovery of water (see pp. 326-331). The concentrations of Ca and phosphate, which form the mineral substance of bone and teeth, are also precisely regulated. 

An instructive example is the physiological variable serum creatinine. Creatinine is an endogenous metabolite formed from, and thus reflecting, muscle mass. Total body muscle mass is sufficiently constant to render measurement of serum creatinine useful for assessing actual renal function. The serum value of creatinine (R) is namely dependent on the continuous (zero-order) input of creatinine into the blood (A in) and its renal elimination rate, which is a first-order rate process (A out x ) In case of an extensive muscle breakdown, kin will temporarily increase. It may also be permanently low, for example in old age when muscle mass is reduced. Likewise, creatinine clearance may decrease for various reasons, described by a decrease in A out- An increase in creatinine clearance may occur as well, for example following recovery from renal disease. According to pharmacodynamic indirect response models. 

Morsehi PL. Development of physiological variables important for drug kinetics. In Morsehi PL, Pippenger CE, Penry JK, editors. Antiepileptic drug therapy in pediatrics. New York Raven Press 1983. p. 1-12. 

The concentration of fluoride in nails and hair appears to be proportional to intake over longer periods of time, taking into account their growth rate [100-103]. Exposure to fluoride may occur in the local environment at the place of residence or via occupational exposure. Daily intake from food, water, dentifrices or fluoride supplements also contributes. The major advantage of nails and hair over fluids and tissues as biomarkers for fluoride exposure is that they can easily be obtained in a non-invasive manner. In contrast to plasma, saliva and urine, whose fluoride concentrations provide a snapshot at a certain point of time and are subject to change due to recent fluoride intake and certain physiological variables, the concentration of fluoride in nails and hair is cumulative and reflects the average level of intake over a time period, but depends on how often the nails are clipped or hair cut. 

BOX 5.1. PHYSICOCHEMICAL PROPERTIES OF PHARMACEUTICALS, PHYSIOLOGIC VARIABLES, AND PHARMACOKINETIC PARAMETERS... 

Pharmacokinetic Parameter Mathematical Relationship Physiological Variables... 

Duffy PH, Feuers RJ, Leakey JA, Nakamura K, Turturro A, Hart RW. Effect of chronic caloric restriction on physiological variables related to energy metabolism in the male Fischer 344 rat. Mech Ageing Dev 1989 48 117-133. 

Shkorbatov, G.L. (1961). Intraspecies physiological variability in aquatic poikilo-therms (In Russian). Zoologicheskii Zhumal 40,1437-1452. 

Janie EM, Kissinger PT. Monitoring physiological variables with membrane probes. Acta Astronautica 1998, 43, 87-99. 

Substances that undergo bioconcentration are hydrophobic and lipophilic, and therefore tend to undergo transfer from water media to fish lipid tissue. The simplest model of bioconcentration views the phenomenon on the basis of the physical properties of the contaminant and does not account for physiologic variables (such as variable blood flow) or metabolism of the substance. Such a simple model forms the basis of the hydrophobicity model of bioconcentration, in which bioconcentration is regarded from the viewpoint of a dynamic equilibrium between the substance dissolved in aqueous solution and the same substance dissolved in lipid tissue. 

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