have been calculated for the steroid hormones (Dunn
et al.
1981), thyroxine (Oppenheimer 1989), and
vitamin D
3
(Dunn 1988).
Laboratory measurement of the bioactive fraction
The plasma concentrations of calcium, magne-
sium, and the hormones are regulated by homeo-
static systems. Because the concentration of the
bioactive fraction in the regulator tissue is the entity
that is homeostatically controlled, a change in
binding protein capacity or affinity will lead to a
secondary alteration in the total concentration of the
regulated substance. The concentration will change
just enough to reestablish the set-point plasma
concentration of the bioactive fraction. Significant
abnormalities in binding protein affinity are unusual
but variability in binding protein capacity are
common in clinical practice (Table 7.3). Therefore,
the extent of plasma protein binding must be consid-
ered when measuring the concentration of these
analytes.
Calcium and magnesium.
Calcium and magne-
sium are physiologically active in their ionic
(unbound) forms only. The bound forms of these
cations are made up of diffusable species (complexed
calcium and magnesium) and nondiffusable protein-
bound complexes. For calcium, protein binding
accounts for about 45 percent of the total calcium
and complexed calcium for 10 percent. Total
calcium concentrations are altered only very little by
small changes in the plasma albumin concentration
and small to moderate changes in the concentrations
of the calcium-complexing anions (phosphate,
carbonate, and citrate). In those cases, the concen-
tration of total calcium adequately reflects the ionic
calcium concentration. Moderate changes in plasma
albumin concentration and large changes in the
concentrations of the calcium-complexing anions
may alter the total calcium levels enough to obscure
the true status of the homeostatic control of the ionic
calcium concentration. In such settings, the concen-
tration of ionic rather than total calcium can be
measured using ion-selective electrode potenti-
ometry. Alternatively, the concentration of ionic
calcium can be calculated using any of a number of
formulas if changes in albumin concentration are the
sole binding abnormality (Vanstapel and Lissens
1984).
Albumin-bound magnesium represents only 25
per cent of the total magnesium and complexed
forms about 15 per cent. Only large alterations in
the plasma concentration of albumin or the
magnesium-complexing
anions
(phosphate,
carbonate, and citrate) will change the total magne-
sium levels enough to disallow the use of the total
magnesium concentration as the indicator of the
ionic magnesium concentration.
Hormones.
In tissues with short mean capillary
transit times, i.e., in essentially all tissues but the
liver, the bioactive form of a hormone is the
Organ Function
7-14
Table 7.2
Relative Affinities and Capacities of Plasma Proteins
Binding the Thyroid and Steroid Hormones
Affinity
Capacity
High
Moderate-to-low
High
TBG
TBG
triiodothyronine thyroxine
SHBG
SHBG
estradiol
testosterone
prealbumin
CBG
thyroxine
cortisol
Intermediate CBG
testosterone
aldosterone
prealbumin
triiodothyronine
Low
albumin
thyroid hormones
steroid hormones
Table 7.3
Common Causes of Altered Plasma Concentrations of
Binding Proteins
Protein
Increase
Decrease
all
acute dehydration malnutrition
liver failure
nephrosis
protein-losing
enteropathy
albumin
acute-phase response
TBG
hypothyroidism hyperthyroidism
pregnancy
hyperestrogenemia
CBG pregnancy
hyperestrogenemia
SHBG pregnancy
hyperandrogenemia
hyperestrogenemia hypothyroidism
hyperthyroidism (females)
liver failure
(males)
