Circulating forms of micronutrients in deficiency
states
Micronutrient deficiency does not occur all of a
sudden; it is the result of a long-term inequality
between the dietary intake of a micronutrient and its
loss from the body. During the period that the
deficiency is developing, the body passes through a
characteristic series of pathobiologic stages each of
which is associated with a predictable pattern of
findings among the circulating forms of the micronu-
trient (Hastka
et al.
1996, Herbert 1994, Herbert
1987). The stages as they apply to iron, cobalamin,
and folate deficiency are illustrated in Figure 8.2.
At first, the body merely experiences a negative
balance in the micronutrient; the shortfall in dietary
intake is compensated for by tapping the body stores
and supply reserves of the micronutrient. For
cobalamin and folate, the transport form of the
micronutrient is decreased in this stage due to the
decreased contribution of the dietary component of
the form. For iron, the plasma transferrin concen-
tration remains essentially normal because of ready
access to the hepatic iron stores. As the negative
balance persists, the stores and supply reserves are
progressively depleted. During this stage, the
concentration of the circulating storage form of the
micronutrient decreases. At some point, the stores
and supply reserves of the micronutrient become
depleted to the point that there is insufficient
delivery of the micronutrient to the active tissues.
Then the circulating supply and product forms of the
micronutrient begin to decline. During the stage of
deficient erythropoiesis, only the marrow and the
most recently manufactured red cells show the
effects of insufficient micronutrient supply. As the
normal red cells (those that were produced prior to
the onset of deficient erythropoiesis) senesce, the
reduced rate of effective red cell production leads to
anemia. With continued micronutrient deficiency,
individual red cell abnormalities become more
pronounced and the rate of effective red cell produc-
tion falls ever lower resulting in progressively more
severe anemia.
Other markers of micronutrient status in
deficiency states
In addition to direct measurement of circulating
forms of trace substances, there are a number of
other laboratory approaches for the evaluation of
micronutrient status (Gibson 1990, Taylor 1996).
One such approach, the measurement of the
in vivo
activity of an enzyme that depends upon a trace
substance, was mentioned in a preceding section as
the preferred means of assessing the supply status of
cobalamin. The enzyme, methylmalonyl CoA
mutase, catalyzes the conversion of methylmalonyl
CoA to succinyl CoA. When tissue concentrations
of the mutase are depressed due to cobalamin
Nutritional Status
8-5
normal
negative
balance
depletion
deficient
erythropoiesis
deficiency
anemia
iron stores
plasma
transferrin
marrow
iron
liver
folate
plasma
folate
marrow
folate
liver
cobalamin
marrow
cobalamin
plasma
holo-TC II
Figure 8.2
Pathobiologic stages in the development of micronutrient deficiency.
Adapted from figures in Herbert (1987). holo-TC II, holo-transcobalamin II
.
