Page 103 - Color_Atlas_of_Physiology_5th_Ed._-_A._Despopoulos_2003

Iron Metabolism and Erythropoiesis transferrin receptors. Once iron has been re-
leased to the target cells, apotransferrin again
Roughly /3 of the body’s iron pool (ca. 2 g in becomes available for uptake of iron from the
2
women and 5 g in men) is bound to hemoglobin intestine and macrophages (see below).
(Hb). About /4 exists as stored iron (ferritin, he- Iron storage and recycling (! A3). Ferritin,
1
mosiderin), the rest as functional iron (myoglo- one of the chief forms in which iron is stored in
bin, iron-containing enzymes). Iron losses the body, occurs mainly in the intestinal mu-
from the body amount to about 1 mg/day in cosa, liver, bone marrow, red blood cells, and
men and up to 2 mg/day in women due to plasma. It contains binding pockets for up to
menstruation, birth, and pregnancy. Iron ab- 4500 Fe 3+ ions and provides rapidly available
sorption occurs mainly in the duodenum and stores of iron (ca. 600 mg), whereas iron mobi-
varies according to need. The absorption of iron lization from hemosiderin is much slower
supplied by the diet usually amounts to about (250 mg Fe in macrophages of the liver and
3 to 15% in healthy individuals, but can in- bone marrow). Hb-Fe and heme-Fe released
crease to over 25% in individuals with iron from malformed erythroblasts (so-called in-
deficiency (! A1). A minimum daily iron in- efficient erythropoiesis) and hemolyzed red
take of at least 10–20 mg/day is therefore rec- blood cells bind to haptoglobin and
ommended (women ! children ! men). hemopexin, respectively. They are then en-
Iron absorption (! A2). Fe(II) supplied by gulfed by macrophages in the bone marrow or
the diet (hemoglobin, myoglobin found chiefly
Blood in meat and fish) is absorbed relatively effi- in the liver and spleen, respectively, resulting
in 97% iron recycling (! A3).
An iron deficiency inhibits Hb synthesis,
4 ciently as a heme-Fe(II) upon protein cleavage. leading to hypochromic microcytic anemia:
With the aid of heme oxygenase, Fe in mucosal
cells cleaves from heme and oxidizes to Fe(III). MCH " 26 pg, MCV " 70 fL, Hb " 110 g/L. The
The triferric form either remains in the mucosa primary causes are:
as a ferritin-Fe(III) complex and returns to the ! blood loss (most common cause); 0.5 mg Fe
lumen during cell turnover or enters the are lost with each mL of blood;
bloodstream. Non-heme-Fe can only be ab- ! insufficient iron intake or absorption;
2+
sorbed as Fe . Therefore, non-heme Fe(III) ! increased iron requirement due to growth,
must first be reduced to Fe 2+ by ferrireductase pregnancy, breast-feeding, etc.;
(FR; ! A2) and ascorbate on the surface of the ! decreased iron recycling (due to chronic in-
luminal mucosa (! A2). Fe 2+ is probably ab- fection);
sorbed through secondary active transport via ! apotransferrin defect (rare cause).
2+
an Fe -H symport carrier (DCT1) (competi- Iron overload most commonly damages the liver,
+
tion with Mn , Co , Cd , etc.). A low chymous pancreas and myocardium (hemochromatosis). If
2+
2+
2+
pH is important since it (a) increases the H + the iron supply bypasses the intestinal tract (iron in-
gradient that drives Fe 2+ via DCT1 into the cell jection), the transferrin capacity can be exceeded
and (b) frees dietary iron from complexes. The and the resulting quantities of free iron can induce
absorption of iron into the bloodstream is iron poisoning.
regulated by the intestinal mucosa. When an B 12 vitamin (cobalamins) and folic acid are also
iron deficiency exists, aconitase (an iron-regu- required for erythropoiesis (! B). Deficiencies
lating protein) in the cytosol binds with fer- lead to hyperchromic anemia (decreased RCC,
ritin-mRNA, thereby inhibiting mucosal fer- increased MCH). The main causes are lack of
ritin translation. As a result, larger quantities intrinsic factor (required for cobalamin resorp-
of absorbed Fe(II) can enter the bloodstream. tion) and decreased folic acid absorption due
Fe(II) in the blood is oxidized to Fe(III) by to malabsorption (see also p. 260) or an ex-
ceruloplasmin (and copper). It then binds to tremely unbalanced diet. Because of the large
apotransferrin, a protein responsible for iron stores available, decreased cobalamin absorp-
transport in plasma (! A2, 3). Transferrin tion does not lead to symptoms of deficiency
(= apotransferrin loaded with 2 Fe(III)), is until many years later, whereas folic acid defi-
90 taken up by endocytosis into erythroblasts and ciency leads to symptoms within a few
cells of the liver, placenta, etc. with the aid of months.
Despopoulos, Color Atlas of Physiology © 2003 Thieme
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