The Logic of laboratory Medicine - page 116

arises predominantly from dietary intake, its plasma
concentration will merely reflect recent dietary
intake of the substance, regardless of the state of the
body stores.
Table 8.2 lists the circulating forms for the
micronutrients involved in red cell production. Iron
circulates in four forms. The iron present in red cell
hemoglobin is a product form. The ferritin
contained within red cells represents erythroblast
iron left over from the process of hemoglobinization.
As such, it is a supply form of iron. Most of the
iron in the plasma is present as transferrin, the trans-
port form of iron. Plasma iron is also present as
ferritin, the storage form of iron. Normally the
ferritin in plasma arises from hepatic iron stores.
However, in chronic anemias treated by repeated red
cell transfusions, large amounts of ferritin are depos-
ited in the marrow and spleen fixed tissue macro-
phages. Then this source of ferritin contributes
significantly to the circulating ferritin.
Cobalamin is present in the circulation in three
forms. The cobalamin in red cells is a supply form.
Plasma cobalamin is present as holo-transcobalamin
II, the transport form of cobalamin, and the more
abundant holo-haptocorrin which is a complex of
cobalamin and haptocorrin. In cobalamin-replete
individuals, holo-haptocorrin typically constitutes
about 0.85 of the circulating cobalamin (Wickra-
masinghe and Fida 1993). Among other physiologic
functions, haptocorrin is probably a minor intracellu-
lar cobalamin-binding protein (Jacobs
et al.
1980,
Fernandes-Costa and Metz 1982), so holo-hapto-
corrin represents a storage form of cobalamin. The
usual sites of origin of plasma holo-haptocorrin are
not known. An isoform of haptocorrin with low
affinity for cobalamin is present in the specific
granules of granulocytes. In the myeloproliferative
disorders, increased turnover of immature granulo-
cytic cells can result in elevated plasma
holo-haptocorrin concentrations due to holo-
haptocorrin of granulocyte origin.
Circulating folate is present as transport forms in
the plasma and as a supply form in red cells.
The transport markers of these micronutrients
that are most often used clinically are plasma iron
concentration, plasma holo-transcobalamin II
concentration, and plasma folate concentration.
Because transferrin contains most of the iron in the
plasma in normal individuals and in iron deficiency,
total plasma iron concentration is a very satisfactory
way to measure this transport species. Plasma
cobalamin concentration serves as the storage
marker for cobalamin. Total plasma cobalamin
concentration is a satisfactory measure of plasma
holo-haptocorrin concentration because the majority
of the plasma cobalamin is in this form. The plasma
concentration of ferritin-bound iron could be used as
a storage marker for iron but the separation of
ferritin-bound iron from transferrin-bound iron is
technically difficult. Instead, as discussed in a
subsequent section, the plasma concentration of
ferritin measured as a protein is used as the storage
marker for iron. There is no marker of folate stores.
Red cell folate concentration is used as the marker of
the marrow supply of folate. Red cell ferritin and
cobalamin have not proven to be very reliable
markers of micronutrient supply in the marrow so
they are not employed clinically. Instead, measures
of a product form are used to gauge the state of
marrow supplies. For iron, red cell hemo-
globinization is usually evaluated. It can be assessed
using either measures of individual red cell hemoglo-
bin (mean red cell volume or mean red cell
hemoglobin) or measures of total red cell hemoglo-
bin
(hematocrit
and
blood
hemoglobin
concentration). For cobalamin, the
in vivo
activity
of an intracellular enzyme that uses cobalamin as a
cofactor is evaluated.
Nutritional Status
8-4
Table 8.2
Circulating Forms of Micronutrients Essential for Red Cell Production (TC, transcobalamin)
Micronutrient
Transport Form Storage Form
Supply Form
Product Form
Iron
transferrin
ferritin
red cell ferritin
red cell hemoglobin
Cobalamin
holo-TC II
holo-haptocorrin
red cell cobalamin
Folate
free folate
red cell folate
folate-albumin
1...,106,107,108,109,110,111,112,113,114,115 117,118,119,120,121,122,123,124,125,126,...238
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