steady-state relationship of the blood concentration
of an absorbed substance and the substance's clear-
ance rate,
blood concentration
=
absorption rate
clearance rate
Rearrangement of this equation yields
absorption rate =
clearance rate x blood concentration
If it is assumed that the substance is absorbed
continuously and that the clearance rate of the
substance is a constant, the absorption rate of the
substance can be estimated from its concentration in
the blood. This is a very convenient way to assess
absorptive function but the assumptions that enter
into the calculation restrict its applicability. For
example, gastrointestinal absorption is episodic, not
continuous.
Another approach to the indirect measurement of
absorptive function is to administer a marker
substance and, by measuring the plasma concentra-
tions of the substance over time, deduce the extent of
absorption of the substance. The relationship
between the amount of substance administered and
the substance's plasma concentrations is
AUC
=
fraction absorbed x amount administered
clearance rate
where AUC is the area under the disposition curve.
Rearrangement of this equation gives,
fraction absorbed
=
clearance rate x AUC
amount administered
If the clearance rate of the substance is constant, the
relationship between the fraction of the substance
absorbed and the AUC (normalized to the amount of
substance administered) will be linear. Importantly,
no assumptions need to be made concerning the
kinetics of absorption for the relationship to hold.
Determinants of absorption
When abnormal absorptive function is identified
in a patient, it maybe desirable to evaluate the
patient further to determine if the abnormality can be
localized to the lumen, to the absorptive epithelium,
to the vascular bed, or to transport proteins in the
blood.
Factors in the lumen that influence absorption
include the amount of input and the intraluminal
processing that must occur to render a substance
absorbable. The first of these, the amount of input,
is not a derangement of absorptive function
per se
but it is an important mechanism of abnormal
absorptive intake. Decreased input (i.e., dietary
deficiency or hypoventilation) as a cause of subnor-
mal absorption of a substance is evaluated by enrich-
ing the input with the substance. If absorptive
function is normal, the delivery of increased
amounts of substance to the absorptive organ will
result in an increase in the amount of the substance
absorbed. This can be detected as an increase in the
concentration of the substance in the plasma or as an
increase in a measure of the total body stores of the
substance. Disordered intraluminal processing of a
nutrient (i.e., maldigestion) is commonly the cause
of decreased gastrointestinal absorption. The disor-
der may be nearly global, such as occurs in pancre-
atic insufficiency, may affect a class of nutrients,
such as the effect of bile salt deficiency upon the
absorption of the fat-soluble vitamins, or may be
specific for a single nutrient, such as the inability to
absorb vitamin B12 due to intrinsic factor deficiency
in pernicious anemia. The administration of a
preprocessed form of an affected nutrient will allow
for normal absorption of the nutrient if maldigestion
is the cause of the nutrient's subnormal absorption.
This is the basis of the Schilling test for pernicious
anemia in which the extent of absorption of vitamin
B12 administered already bound to intrinsic factor is
compared to that of vitamin B12 administered alone.
The uptake of substances by an absorptive
epithelium is accomplished by simple diffusion, by
passive transport, or by active transport. Uptake by
simple diffusion is impaired by a reduction in the
surface area for absorption. This can occur as a
result of segmental loss of functioning organ tissue
or by localized or generalized remodeling of the
architecture of the absorptive surface, such as in the
flattening of intestinal villi in celiac disease and the
loss of alveolar walls in emphysema. Passive and
active transport may also decrease when the absorp-
tive surface area is reduced. However, if homeo-
static regulation of an absorbed substance includes
regulation of the expression of the epithelial
membrane transport proteins or intracellular binding
proteins that effect the transport, increased expres-
sion of the proteins will partly compensate for
decreases in the surface area. Hypoabsorption or
hyperabsorption of a regulated substance may occur
as a result of a disordered homeostatic system's
effect upon the epithelial expression of its transport
proteins. The absorptive dysfunction may even
Organ Function
7-5
