Page 643 - Williams Hematology ( PDFDrive )

618 Part VI: The Erythrocyte Chapter 42: Iron Metabolism 619

TABLE 42–1. Iron Compartments in the Average Person* TRANSPORT COMPARTMENT
Iron Content Total Body Iron From the standpoint of its total iron content, normally about 3 mg, the
Compartment (mg) (%) transport compartment of plasma is the smallest but the most active of
the iron compartments: Its iron, almost entirely carried by transferrin,
Hemoglobin iron 2000 67
normally turns over at least 10 times each day. This is the common path-
Storage iron (ferritin, 1000 27 way for interchange of iron between compartments.
hemosiderin)
Myoglobin iron 130 3.5 Transferrin
Transferrin is a dumbbell-shaped glycoprotein with a Mr of approx-
Labile pool 80 2.2
imately 80 kDa where each of the two globular domains contains a
Other tissue iron 8 0.2 binding cleft for Fe . Normally, approximately one-third of the
3+ 9–11
Transport iron 3 0.08 transferrin iron-binding sites are occupied by iron. Human plasma
normally contains approximately 25 to 45 μM (200 to 360 mg/dL)
*These values represent estimates for an “average” person, that is, transferrin, capable of binding 50 to 90 μM iron but carrying only 10
70 kg (154 lb) in weight and 177 cm (70 inches) in height. The values to 30 μM (50 to 180 mcg/dL) iron. Apotransferrin (transferrin devoid
are derived from data in several sources. of iron) is synthesized by hepatocytes and by cells of the monocyte–
macrophage system. 12,13
of serum ferritin levels important in the diagnosis of disorders of iron
metabolism. DIETARY IRON
The size of the iron storage compartment is quite variable. Nor-
mally, in adult men, it amounts to 800 to 2000 mg; in adult women, CONTENT
it is a few hundred milligrams. The mobilization of storage iron from Average American adult men and women ingest 9 to 10 mg and 12 to
ferritin involves the reduction of Fe to Fe , its release from the core 14 mg of iron daily, respectively. The amount of iron absorbed by a
2+
3+
14
crystal and its diffusion out of the apoferritin shell. As it passes from normal adult male need only balance the small amount that is excreted,
cytosol to plasma, it must be reoxidized to Fe , either by hephaestin mostly in the stool, approximately 1 mg/day. More iron is needed
3+
15
or ceruloplasmin in the cell membrane or by ceruloplasmin in plasma, during growth periods or after blood loss. In women, iron absorbed
before it binds to transferrin. Alternatively, iron may be released from must be sufficient to replace that lost through menstruation or diverted
ferritin by autophagy followed by lysosomal degradation. 3 to the fetus or milk during and after pregnancy. Table 42–2 shows the
Hemosiderin is found predominantly in macrophages. Microscop- age- and gender-specific recommended dietary allowances for iron. 16
ically, in unstained tissue sections or marrow films it appears as clumps
or granules of golden refractile pigment. Under pathologic conditions, BIOAVAILABILITY
it may accumulate in large quantities in almost every tissue of the body.
Hemosiderin is chemically similar to the iron core of ferritin and may In meat-eaters in Western countries, heme from hemoglobin and myo-
be derived from ferritins whose protein shells have been digested in globin normally comprises approximately 15 percent of dietary iron but
lysosomes. is much more efficiently absorbed than nonheme iron, and promotes
the absorption of nonheme iron. The absorption of nonheme dietary
17
MYOGLOBIN iron is strongly affected by iron-binding components of food. Oxalates,
Myoglobin is structurally similar to hemoglobin, but it is monomeric phytates, and phosphates complex with iron and retard its absorption,
whereas simple reducing substances, such as hydroquinone, ascorbate,
rather than tetrameric: Each myoglobin molecule consists of a heme lactate, pyruvate, succinate, fructose, cysteine, and sorbitol, increase
group nearly surrounded by polypeptide loops of the 154 amino acid iron absorption. Iron-fortified cereals are major sources of iron in
18
protein. It is present in small amounts in all skeletal and cardiac muscle countries where fortification is practiced, but cooking in iron pots
cells, where it may serve as an oxygen reservoir to protect against cellu- may also provide important exogenous iron. Gastric acid secretion,
17
lar injury during periods of oxygen deprivation and may scavenge nitric
oxide and reactive oxygen species. 4
LABILE IRON POOL TABLE 42–2. Recommended Dietary Allowances (RDAs)
The existence of a cellular labile iron pool was postulated from studies for Iron 16
of the rate of clearance of injected Fe from plasma. Iron leaves the Age Male Female Pregnancy Lactation
59
5
plasma and enters the interstitial and intracellular fluid compartments
for a brief time before it is incorporated into heme or storage com- Birth to 6 months 0.27 mg* 0.27 mg*
pounds. Some of the iron reenters plasma, causing a biphasic curve of 7–12 months 11 mg 11 mg
59 Fe clearance 1 to 2 days after injection. The change in slope defines the 1–3 years 7 mg 7 mg
size of the labile pool, normally 80 to 90 mg of iron. It is now sometimes
considered to be equivalent to the chelatable iron pool. 6 4–8 years 10 mg 10 mg
9–13 years 8 mg 8 mg
TISSUE IRON COMPARTMENT 14–18 years 11 mg 15 mg 27 mg 10 mg
Tissue iron (exclusive of hemoglobin, ferritin, hemosiderin, myoglobin, 19–50 years 8 mg 18 mg 27 mg 9 mg
and the labile compartment) normally amounts to 6 to 8 mg. This includes 51+ years 8 mg 8 mg
cytochromes and other iron-containing enzymes. Although a small com-
partment, it is an extremely vital one and is sensitive to iron deficiency. 7,8 *Adequate intake (AI).

Kaushansky_chapter 42_p0617-0626.indd 618 9/17/15 6:26 PM