DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 37–3
Iron Requirements for Pregnancy
AVERAGE RANGE
(mg) (mg)
External iron loss 170 150–200
Expansion of red cell mass 450 200–600
Fetal iron 270 200–370
Iron in placenta and cord 90 30–170
Blood loss at delivery 150 90–310
Total requirement a 980 580–1340
Cost of pregnancy b 680 440–1050
a
Blood loss at delivery not included.
b
Iron lost by the mother; expansion of red cell mass not included.
Source: Council on Foods and Nutrition. Iron deficiency in the
United States. JAMA 1968, 203:407–412. Used with permission.
Copyright © (Year of Publication) American Medical Association.
All rights reserved.
inorganic iron or heme iron. A ferrireductase, duodenal
cytochrome B (Dcytb), located on luminal surface of
absorptive cells of the duodenum and upper small intestine,
reduces the iron to the ferrous state, which is the
substrate for the divalent metal (ion) transporter 1
(DMT1). DMT1 transports the iron to basolateral membrane,
where it is taken up by another transporter, ferroportin
(Fpn; SLC40A1), and subsequently reoxidized to
Fe 3+ , primarily by hephaestin (Hp; HEPH), a transmembrane
copper-dependent ferroxidase. Apo-transferrin (Tf)
binds the resultant oxidized iron.
Mucosal cell iron transport and the delivery of
iron to transferrin from reticuloendothelial stores are
both determined by the human hemochromatosis protein,
which is a major histocompatibility complex class
1 molecule encoded by the HFE gene (for High Fe)
located on the short arm of chromosome 6 at 6p21.3.
Regulation is finely tuned to prevent iron overload in
times of iron excess while allowing for increased
absorption and mobilization of iron stores with iron
deficiency. A predominant negative regulator of iron
absorption in the small intestine is hepcidin, a
25–amino acid peptide made by hepatocytes (Ganz,
2003). The synthesis of hepcidin is greatly stimulated
by inflammation or by iron overload. A deficient hepcidin
response to iron loading can contribute to iron
overload and one type of hemochromatosis. In anemia
of chronic disease, hepcidin production can be
increased up to 100-fold, potentially accounting for
characteristic features of this condition, namely poor
GI uptake and enhanced sequestration of iron in the
reticuloendothelial system.
Normal iron absorption is ~1 mg per day in adult
men and 1.4 mg per day in adult women; 3-4 mg of
dietary iron is the most that normally can be absorbed.
Increased iron absorption is seen whenever iron stores
are depleted or when erythropoiesis is increased or ineffective.
Patients with hereditary hemochromatosis due
to HFE mutations demonstrate increased iron absorption
and loss of the normal regulation of iron delivery
to transferrin by reticuloendothelial cells (Ajioka and
Kushner, 2003). The resulting increased saturation of
transferrin permits abnormal iron deposition in nonhematopoietic
tissues.
Iron Requirements and the Availability of Dietary Iron.
Iron requirements are determined by obligatory physiological
losses and the needs imposed by growth. Thus
adult men require only 13 μg/kg per day (~1 mg),
whereas menstruating women require ~21 μg/kg per
day (~1.4 mg). In the last two trimesters of pregnancy,
requirements increase to ~80 μg/kg per day (5-6 mg),
and infants have similar requirements due to their rapid
growth. These requirements (Table 37–4) must be considered
in the context of the amount of dietary iron
available for absorption.
In developed countries, the normal adult diet contains ~6 mg
of iron per 1000 calories, providing an average daily intake for adult
men of between 12 and 20 mg and for adult women of between 8 and
15 mg. Foods high in iron (>5 mg/100 g) include organ meats such
as liver and heart, brewer’s yeast, wheat germ, egg yolks, oysters, and
certain dried beans and fruits; foods low in iron (<1 mg/100 g) include
milk and milk products and most nongreen vegetables. The content
of iron in food is affected further by the manner of its preparation
because iron may be added from cooking in iron pots.
Although the iron content of the diet obviously is important,
of greater nutritional significance is the bioavailability of iron in
food. Heme iron, which constitutes only 6% of dietary iron, is far
more available and is absorbed independent of the diet composition;
it therefore represents 30% of iron absorbed (Conrad and
Umbreit, 2002).
The nonheme fraction nonetheless represents far the largest
amount of dietary iron ingested by the economically underprivileged.
In a vegetarian diet, nonheme iron is absorbed very poorly because of
the inhibitory action of a variety of dietary components, particularly
phosphates. Ascorbic acid and meat facilitate the absorption of nonheme
iron. Ascorbate forms complexes with and/or reduces ferric to
ferrous iron. Meat facilitates the absorption of iron by stimulating
production of gastric acid; other effects also may be involved. Either
of these substances can increase availability several fold. Thus assessment
of available dietary iron should include both the amount of iron
ingested and an estimate of its availability (Figure 37–4) (Monsen
et al., 1978).
A comparison of iron requirements with available dietary
iron is seen in Table 37–4. Obviously, pregnancy and infancy represent
periods of negative balance. Menstruating women also are at
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CHAPTER 37
HEMATOPOIETIC AGENTS