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1985 66: 935-939

Transferrin saturation, plasma iron turnover, and transferrin uptake in normal humans
M Cazzola, HA Huebers, MH Sayers, AP MacPhail, M Eng and CA Finch

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From bloodjournal.hematologylibrary.org by guest on July 6, 2013. For personal use only.

Transferrin

Saturation,

Plasma

Iron

Turnover,

and Transferrin
By Mario Cazzola, Helmut
Mary

Uptake
A. Huebers,
Eng, and

in Normal
Merlin H. Sayers,
A. Finch

Humans
A. Patrick MacPhail,

Clement

The relationship between plasma iron. transferrin saturation, and plasma iron turnover was studied in 53 normal subjects whose transferrin saturation varied between 17% and 57%, in 25 normal subjects whose transferrin saturation was increased by iron infusion to between 67% and 1 00%. and in five subjects with early untreated idiopathic hemochromatosis whose transferrin saturation was continually elevated to between 61 % and 86%. The plasma iron turnover of all of these subjects ranged from 0.45 to
1

.22

mg/dL

whole

blood/d.

The

mean

values

for

the

above-mentioned three groups were 0.71 0.1 7. 1 .01 0.1 1. and 1 .01 0.13 mg/dL whole blood/d, respectively. Most of this variation, estimated at 72% by regression analysis. was due to a direct relationship between transferrin
attributed

saturation

and

plasma

iron

turnover.

This

effect

was

to a competitive advantage of diferric over monoferric transferrin in delivering iron to tissues. This was confirmed by the demonstration of a more rapid clearance of diferric as compared to monoferric transferrin in an additional group of eight normal subjects. Calcula-

tions were made of the amount of transferrin reacting with membrane receptors per unit time. Allowance was made for the noncellular (extravascular) exchange and for the 4.2:1 preference of diferric over monoferric transferrin demonstrated in vitro. The amount of iron-bearing transferrin leaving the plasma to bind to tissue receptors for 53 subjects with a transferrin saturation between 1 7% and 57% was 71 1 3; for 25 subjects with a saturation from 67% to 100%, 72 12; and for five subjects with early idiopathic hemochromatosis. 82 1 1 zmol/L whole blood/ d. There were no significant differences among these groups. These studies indicate that while the number of iron atoms delivered to the tissues increases with increasin9 plasma iron and transferrin saturation, the number of iron-bearing transferrin molecules that leave the plasma per unit time to bind to tissue receptors is relatively constant and within the limits studied. independent of
transferrin a 1985 saturation.

by Grune

& Stratton.

Inc.

F
acterize

ERROKINETIC internal iron

erythropoiesis.

studies have been used exchange, and more particularly, The assumption rests has been Recent studies

to

evaluate to charthe iron this

followed
maintain

by a continuous
the plasma iron

infusion

in an

amount
level.

calculated
Measurements during

to
of the

at a near-saturated

validity
behaves

of such
as a

calculations
single

on which that plasma have shown

pool.

plasma iron saturation were made at different times study. Five subjects who were incidentally found to have
transferrin ied. These saturation individuals after had repeated no symptoms determinations or splenomegaly were

an elevated
also studon physical

assumption is composed
ferric

to be invalid.79 The plasma of three different molecular one diferric transferrin. iron similarly in vivo, in their iron-donating
were determined

transferrin species, The but are capacity. two

iron pool two monomonoferric

and

species diferric
in vivo netic basis

donate moiety
relationships

inferior to the In this work, ferrokiOn the

developed

examination, had a normal Hct (43.6% I .3%), a normal reticulocyte count (1.1% 0.3%), a plasma ferritin concentration >500 zg/L, and a liver biopsy showing parenchymal iron deposition but no
hepatic fibrosis. These subjects were considered to represent individ-

studies
of previous

in normal
in vitro

and

by performing hyperferremic humans.

was

uals with precirrhotic idiopathic Ferrokinetic studies. The

individual measurement

hemochromatosis. amount of radioiron

iron turnover was

used
4 Ci

for

an

studies,#{176} a formula

of plasma

of Fe

for deriving iron-bearing unit time

from the transferrin to bind

plasma iron turnover molecules that leave receptors.

AND METHODS

the the

number plasma

of per

to tissue
MATERIALS

and/or 2 zCi of pCi/ag of iron. the subject had were evaluated. label transferrin
neously. in vitro (pH

39Fe. Each isotope had a specific activity of about 10 Measurements were carried out in the morning after fasted. Initially, several different methods of tagging In these studies, two different isotopes were used to in different fashions and were injected simultatagging 2) to was 10 mL carried out by adding plasma a tracer with amount constant of heparinized

Experimental

subjects. protocols of

formed
Experimental University informed
good

on 53 normal

In vivo ferrokinetic studies were pervolunteers between the ages of 21 and 40.
for these Human from studies were Subjects all subjects. approved Committee All subjects were by the and in

of 55FeSO4

Washington was obtained

From
versity Submitted

the Department
of Washington. Nov 5, 1984;

of Medicine,
Seattle. accepted

Hematology
April 16, 1985.

Research.

Uni-

consent

health, had a hematocrit (Hct) 40 (males) or 35 (females), transferrin saturation between 20% and 60%. In a few instances, the transferrin saturation, when repeated at the time of the study, was found to be outside of this range. In addition, the plasma iron turnover was determined in 25 subjects after the plasma iron had been artificially raised by an infusion of ferrous ammonium sulfate. In I 6 of these subjects, plasma iron turnover had been first determined under basal conditions a few hours before. For the second turnover, a cold ferrous iron infusion was given over a period and
a

in part by National Institutes of Health Grant No. HL06242, a grant from the Italian Association for Cancer Research, and Grant No. 84.00505.44 from Progetto Finalizzato Oncologia. Computer assistance was provided by CLINFO Computer System, funded under General Clinical Research Grant No. RR-37 from the National Institutes of Health. A portion of the work was conducted in the Clinical Research Center under Grant
No. RR-37

Supported

of ten

minutes

immediately

following

the

injection

of a trace

amount

of a second isotope of iron. The amount of cold iron injected was designed to increase the in vivo saturation to about 90%, that calculation being based on the unsaturated iron-binding capacity and estimated plasma volume. In six subjects, the single dose was
1985: pp 935-939

Address reprint requests to Clement A. Finch, MD, Hematology Research. 4 East, Providence Hospital, ZD-20, 500 1 7th Ave. Seattle, WA 98124.

I 985

by Grune

& Stratton,

Inc.

0006-4971/85/6604-0029$03.00/0

Blood,

Vol 66,

No 4 (October).

935

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936

CAZZOLA

ET AL

Table

1 . Comparisons

Between

Different With Radioiron

Ratio

Methods

of Labeling

bated
formula:

to 0 time,

and

from

the

Hct

according

to the

following

Transferrin

Between

Red cell utilization

(mg/dL PIT WB/d)
0.14

(%)
0.92
-

Measured No. Group of

and WBA on day 14 x 100 0.9 (Hct on day 14/100)

Subjects 4 65FeS04.

Tagging in vivo

Blood

Predicted Volume

WBA
in which

extrapolated
WBA venous is whole Hct

0 time
blood

0.9 (Hct
0.92

at 0 time/lOO)
is the factor for

1.06

0.03 0.02 0.16

0.75 0.7 1 0.75

0.76 in

activity,

69FeSO4,
b

in vitro
in vitro in vitro used to

1 .00
0.98 0.98 label

0.12 0.16 0.17

65FeSO4, 59Fe citrate,

0.15

and 0.98 is the factor accounting for trapped plasma (0.98 x 0.92 - 0.9). The adequacy of binding of radioiron to transferrin in vitro and in
converting to whole vivo
are

body

Hct,

Two
fashions

different
and were

isotopes inejcted

were

transferrin subject.

different

was from

evaluated based isotope

by comparing on weight dilution, and ie,

the

calculated to the

blood blood

volume volume

of the calcu-

simultaneously

in each

Values

individual lated plasma

height2

expressed

as means

SD. Abbreviation:

WB,

whole

blood.

volume

(mL) cpm injected

plasma activity extrapolated plasma
=

agitation

so as to optimize

dispersion

of the with at the same

added plasma time.

iron

and

permit

random
plasma with

loading
and

of binding

sites.
was

Fe citrate

was similarly
tagged In vivo

added
tagging

to

its clearance injected

compared

in vitro blood

to 0 time volume (mL)

(cpm/mL)

59FeSO4

intravenously

was carried out by injecting trace amounts of 59FeSO4 (pH 2) in a volume of 2 mL intravenously by pump over a period of five minutes. From these studies, it was concluded that trace labeling by any of the
methods used gave was their normal containing a Sephadex similar examined the simultaneous subjects. plasma column results by two in normal labeling plasma clearance was subjects5 (Table at low and 1). high and blood saturabuffer passed NJ).7

volume

(mL)

whole

body plasmatocrit

The
transferrin saturation, determining in eight tion,

effect

of altering
injecting

the proportion

of monoferric
plasma aliquots from exposed

and diferric

intravenously, the circulating plasma and of low this was to a phosphate Piscataway,

where the whole body plasmatocrit is equal to (1 00 Hct x 0.9)/ 100. Transferrin binding was considered adequate since calculations based on extrapolated activity differed by less than 10% from blood volumes calculated from height-weight ratios as described by
others.3 plished I). This was true regardless of whether tagging was injection accom(Table by in vitro incubation or by in vivo radioiron

In order

to provide

6 mL of the subjects 7.1) 50 mg G50

(pH
through

ofdesferrioxamine (Pharmacia,

The transferrin aliquot obtained had a plasma iron level of <20 ig/dL and to this, 59FeSO4 in tracer amounts was added and 15
minutes transferrin subjects was allowed for binding. The mean iron saturation of in the final abiquot was plasma was trace-labeled Carrier iron as ferrous 9% 4%. A second with FeSO4 and ammonium

transferrin saturation were measured using t9Fe activity was determined by gamma counting, while Fe activity was processed by the method of Eakins and Brown6 and then measured in a liquid scintillation counter.
standard Calculations of transferrin uptake. Additional calculations

Plasma

iron

and

aliquot
incubated was

of the
for then

is

minutes.

sulfate

were made to convert the plasma iron turnover to transferrin uptake. The plasma iron turnover at basal or elevated levels of plasma iron represented the actual turnover of iron in the plasma at the subjects
plasma iron-bearing ferrin, two iron level. transferrin additional In order calculations to determine by membrane were required. the rate receptors It was of uptake for transfirst necesof molecules

added in an amount calculated to saturate the binding capacity of the plasma. The final saturation was 96% 2%. The details of measurement of plasma iron turnover have been reported elsewhere.4 After intravenous injection of radioiron, five to six blood samples were drawn over the anticipated half-time
isotope plasma disappearance, iron determinations when the plasma iron usually were at least carried 120 out minutes. on the In initial addition, sample

and

at the estimated
of plasma

half-time
iron

during
was the

basal
artificially

turnovers
elevated.

and
In plasma

more
the iron

frequently calculations

sary to subtract that portion of plasma iron that was escaping into the extravascular space. Cook et al had previously derived a factor for extravascular flux (EVF). They identified the early reflux component of the plasma radioiron clearance curve as due to extravascular exchange. Application of regression analysis to this component showed it to be related to plasma iron concentration (r =
.71) and that it could be derived using the following formula:

turnover,

extrapolated

value (PIT)

at the t/4 was used. The calculation of plasma iron turnover was carried out employing the standard formula4: whole blood/d) PI(g/dL)
-

EVF

(mg/dL

wb/d)
-

PI(,g/dL)

x [(100 is presumed
receptors.

Hct to exit

x 0.9)/100] from
iron

x 0.0015.

PIT (mg/dL where

half-time.

x (100

Hct

x 0.9) The
blood clearance calculated

t4(min) and from

t/

x 100

fraction
by binding

remaining

the circulating
uptake
-

to membrane

Tissue

(IU)

is

P1 is plasma
In some

iron concentration
instances, radioiron

is radioiron was

utilization

then determined The second

transferrin

by: IU (mg/DL whole correction was designed

It has been and diferric in reacting derive the

bbood/d) PIT to convert iron

that may a 4.2 iron

EVF. uptake
loading

to
on

from

the blood

activity

at 14 days,

the blood

activity

extrapo-

uptake.

demonstrated transferrin

transferrin
proportion

occurs

in vitro

and in vivo at random,

diferric transferrin with number uptake of

so that with iron,

the exact
51$

of monoferric shown to that

be determined

5Trace
may should be saturation

amounts
injected

of iron may be used to label

intravenously as long ie, >70%. labeling, and as the latter In this

plasma
subjects case,

in vitro
transferrin plasma then

or

from the percentage

also been is monoferric transferrin

of saturation

of transferrin
has membrane

It has
over Thus,

advantage transferrin

is not too great, be used for in vitro

donor should

its saturation

be

it

possible

iron-bearing from the

adjusted to that of the subject, using cold iron. Otherwise, there be incomplete binding of radioiron to transferrin and excessive from circulation.

may loss

molecules
receptors,

that and the

leave

the plasma
transferrin

per unit of time

(TU),

to bind

to tissue
tissue iron

ie, tissue

uptake

transferrin

saturation.

In order

to express

iron

From bloodjournal.hematologylibrary.org by guest on July 6, 2013. For personal use only.

TRANSFERRIN

RECEPTOR

TURNOVER

937

turnover converted IU(mob/L The

tissue 2S(lOO

in terms

of transferrin, of iron:
=

milligrams

of

iron

are

first

to micromoles whole

clearance was 68 these

ence;

of a trace amount 20 minutes (P

<

of diferric .001). Red

transferrin radioiron cell utilization from

bbood/d) ratio

IU(mg/dL transferrin
to
52/100

wb/d) receptor transferrin

respectively,

x (10,000/56). turnover
saturation.

two forms of transferrin the value at two weeks tag

showed no significant differfor the predominantly monoferand turnover in Table between for the diferric form, in 53 group PIT and 85%
.

molecular
iron uptake S)/lOO from from
-

between
related

and
The
-

nc
87%

was 6% (P
>

90% .05).

8%

is then

transferrin

proportions
-

molecular
iron iron uptake uptake

of monoferric and and TfFe2 advantage of diferric

monoferric TfFe, 25(100 25(100
-

diferric
-

being
and

TfFe,
4.2

the

transferrin,
diferric

it is possible
transferrin

to express

Results of plasma normal subjects are there (r PIT

=

iron shown

measurements 2. Within plasma iron

this and

and

as follows:

was

a close
<

correlation
<

.81, P (r - .77,
and was

.001) P

and between transferrin .001). Red cell utilization

of both

saturation averaged

S)/l0O x total
+

iron uptake

5%

independent

plasma (r
= -

S)/lOO

8.452/100

.05)

and

transferrin

saturation

iron (r = .21, P > .05).

14, P>

iron

uptake

from
=

TfFe2

8.452/100
25(100 Considering that
-

Twenty-five been elevated

x total 8.4S2/l00 delivers one iron atom

subjects were studied after their by the intravenous injection ofcold

plasma had iron. At an PIT was subjects under 34% blood/d.

iron uptake.

S)/lOO

average transferrin 1.01 0.11 mg/dL had a prior turnover basal conditions (Fig 12% and the PIT

saturation of 83% 1 1 %, their whole blood/d. Sixteen ofthese performed 1A). The 0.71

monoferric

transferrin

and diferric transferrin delivers two iron atoms at all times, the above-reported relationships permitted to derive the molecular ratio between transferrin and iron uptake: tissue transferrin
iron (iron (iron

immediately initial saturation 0.15 mg/dL

before was whole

was

uptake
uptake uptake uptake from from TfFe,) TfFe,)
+ +
/2(iron

tissue

During the second PIT, transferrin saturation had a mean value of 8 1% I 1 %, with a mean PIT of 1 .0 1 0. 1 1 mg/dL whole bbood/d. These values were significantly different (P aged basal did quent
<

uptake uptake

from from

TfFe2) TfFe2)

.001)
at

from
the

basal
elevated

values.
plasma

On

the
iron

other

hand,

red

cell
aver-

(iron

utilization

concentration

Thus,
transferrin

by substituting
with the

iron uptake

from
relationships,

monoferric

and diferric

88% 6%, measurement disturb average the

not significantly different of 86% 5% (P > .05). normal equilibrium iron and concentration

from the mean The iron infusion there was a subse10 to averaging undergoing infusion

above-reported

it follows:

TU(zmol/L

whole

bbood/d) (200
-

fall in plasma

+ +

2.2S)

IU(zmol/L

whole

bbood/d) saturation.

x (200

6.45)

g/dL/h. tandem

In order to minimize studies were given plasma change turnover

this, six subjects a continued iron iron. of 0 was Their 10 1.01

where

S is the percentage

of transferrin RESULTS

maintain their elevated stable with an average and their plasma iron bbood/d. In the other decrease of 1 3 sg/dL was 1 .00 0. 1 1 mg/dL
An additional five

plasma iron was zg/dL plasma/h, 0.13 zg/dL whole

In eight jzg/dL and

ti,2

subjects whose whose transferrin of a trace radioiron

mean plasma saturation amount was 95

iron was was 31%

90 22 6%, the monothe

19 subjects who had an average plasma/h, the plasma iron turnover whole blood/d.
subjects with early idiopathic hemo-

disappearance transferrin

of predominantly 35 minutes, whereas

ferric

chromatosis

showed

a continued

elevation

of

transferrin

Table 2. Ferrokinetic
Ratio Plasma (ig/dL) Normalsubjectsstudied 112

Measurements
Between and Blood Radloiron t14 (mm) 97

Iron

Transferrin Saturation (%)

Measured
Predicted

Volume

PIT (mg/dL WB/d)

Red cell Utilization (%)

43

35

11

1.07

0.12

23

0.71

0.17

85 (n
-

under
(n
=

basal conditions 53)

subjects studied at 264

39)

Normal
(n

50

83

11

1 .07

0.09

1 62

33

1 .0 1

0. 1 1

84

7 19)

elevated
=

plasma
(n

iron 16)
109

(n

25) subjects basal

-

Normal
Under

conditions

43

34

12

1.07

0.10

92

24

0.71

0.15

86

5
-

At elevated levels

plasma

iron 269 174

(n 51 31 81 72

10)

11

1.09

0.10

163
105

31
20

1.01
1.01

0.11

88 (n
-

6 10)

Precirrhoticidiopathichemochromatosis (n
=

12

1.02

0.11

0.13

80.89

5)

Red cell utilization

of radioiron

was studied

only in some

subjects

(numbers

within

parentheses).

From bloodjournal.hematologylibrary.org by guest on July 6, 2013. For personal use only.

938

CAZZOLA

ET AL

saturation

and

had

a mean

PITof

1.01

0.13

mg/dL

whole
a

1.4

A
a . a.. #{149} .#{149}:sa..:. . .: #{149}.. s
2O

208

bbood/d as shown in Table 2. Red cell utilization was normal (80% and 89%) in the two subjects studied
tissue

of radioiron who were in initial studied approaching iron turnover are of PIT

until
iron

the of

14th all

day,

indicating groups of that

no change subjects trend from

lec 0

distribution.

The displayed

data

three had P
<

a#{176}#{149}
.

E
1

in Fig 2A. saturation

It is apparent

the regression

on transferrin

a curvilinear

I50

a maximum (r = .85, These measurements

.001). of PIT, converted

20

40

50

50

100

20

40

50

50

100

to transferrin uptake by membrane receptors receptor turnover) are displayed in Fig 1 B and no significant
ferrin

(transferrin 2B. There was the basal transand the after iron tandem
differ-

Transfirrln

saturatIon

(%)

difference

(P

>

.05)

between

value loading

uptake of 72

of 71 I I tmol/L group
(Fig

I I mol/L whole bbood/d whole blood/d obtained who underwent

no significant I B). Similarly,

in the was

of 16 subjects in the rate

Fig 2. Relationship between transferrin saturation and (A) plasma iron turnover or (B) transferrin uptake in normal subjects studied on basal conditions (#{149}). normal subjects studied at elevated plasma iron and transferrin saturation (0). and subjects with precirrhotic idiopathic hemochromatosis (A).

ferrokinetic

studies

ence the 13

observed

of transferrin

uptake

between

erythroid
utilization

and
of

nonerythroid
radioiron by red

receptors,
cells

the
would

percentage
change with

of
a

53 normal subjects studied under zmol/L whole bbood/d) and the plasma iron levels (72

basal conditions (71 25 subjects studied at

whole bbood/d).

elevated

1 2 zmol/L

Subjects with early idiopathic hemochromatosis also showed values for transferrin uptake in the normal range. Figure 2B shows the independence of the transferrin receptor turnover on transferrin saturation (P
>

change in transferrin saturation, and this was not found. The explanation for this effect was disclosed by quantitative studies of transferrin iron loading and unloading.7#{176}89 While there have been earlier reports that the loading of transferrins nor
binding

two iron-binding by relative

work the recent

sites binding
in concept

in vitro
rats, that

is neither
and binding

random ironhuman of iron

.05).

determined
sites,922

strengths
rabbits, the

of the

DISCUSSION

A number developed amount

tissues and

of elegant which are going

models through

of iron to take erythroid

of iron from

kinetics and
those

have nonerythroid
tissue5.

been the

beings is consistent with to transferrin conforms loading

tion from model).8 the two It has sites

to simple
also of been transferrin

probability
shown that and

rules
tissue from

(random
distribumonoferric

designed
refluxes

into

consideration

of iron
various

and

diferric

forms

is identical.23 by tissue in plasma as

The

preferential

uptake

of

These measurements, while they may accurately reflect iron turnover, are determined not only by the number of tissue
receptors which take up the transferrin iron complex but also

diferric transferrin progressive increase

receptors then explains the iron turnover which occurs in plasma iron and transferrin model flux and in

by the presented.

plasma iron supply In order to quantitate

as

illustrated by the tissue receptor

the data number,

both animals and humans saturation increase.227 There

in vivo vivo kinetics.

or more specifically, erythropoietic to remove the effect of plasma iron A relationship between plasma plasma et ab, turnover.7
1.4

capacity, it is necessary or transferrin saturation. iron concentration and sometime in the ago by Cook iron of behavior in nonerythroid

are differences First transferrin

between a simple in vitro of all, there is an extravascular and its iron leave the

whereby

vascular reflux, shown

iron but

turnover was Were ascribed there

was appreciated to a change such a difference

250

system described to vary

and return by Morgan in relation

through the lymphatics. This et al28 and Cook et al,7 has been iron concentration.

to plasma

In the second

A
O

place, there is a continuous ing transferrin, which does Iron entering the vascular form a certain ferrin, thereby been previously
where rabbit,

release of tissue iron to circulatnot occur in the in vitro system. system would, therefore, transto diferric transkinetics. This has study
conversion

.
-

a
1.0

#{149}200

proportion changing examined

direct evidence

of monoferric its intravascular

of the expected

by us in a detailed

in the
has

S
-.

0
,.,

100
50

been obtained.7 Since mated those obtained with rabbit reticulocytes, formula based nc transferrin By such
mono/diferric

the in vivo results from incubation it seemed

with rabbits approxiof rabbit transferrin appropriate to use a over monoferincubation.0 expressing of uptake the of

a.

I.-

20

40

60

so

100

20

40

80

80

100

on the 4.2 advantage derived by human

of diferric reticubocyte

Tran sfsrrln
Fig i
.

saturatIon
transferrin

(%)
saturation and (A)

Relationship

between

plasma iron turnover or (B) transferrin studied on basal conditions and after basal value and the values at elevated saturation.

uptake. Each subject was iron loading. Lines join the plasma iron and transferrin

calculations, effect, iron-bearing transferrin

a curve has been defined from which the rate can be calculated. uptake transferrin in normal

The estimate of transferrin changes in plasma iron and by the similar values obtained

was independent of saturation as shown subjects under basal

From bloodjournal.hematologylibrary.org by guest on July 6, 2013. For personal use only.

TRANSFERRIN

RECEPTOR

TURNOVER

939

conditions

and

with

artificially

elevated

plasma

iron.

Like-

provides ferrin The kinetic

an additional saturation. other data. implication While

opportunity concerns

for increasing the interpretation matter to determine

the

trans-

wise,
normal

individuals state,
limits. Thus,

with

constant
while the

hyperferremia slightly
number

due were
atoms iron

to within
dcliv-

an

iron-loading

although

higher,
of

of ferroplasma

it is a simple

ered to tissues increases transferrin saturation,

ferrin molecules

with increasing plasma iron and the number of iron-bearing transbinding to tissue receptors is relatively have certain practical
in a fashion

iron turnover provided radioiron is added properly, it is another matter to evaluate tissue capacity to assimilate iron. A near doubling of iron turnover (and erythroid marrow uptake since utilization merely by increasing does not imply that transferrin increased, receptors
tive poiesis,

constant. These
First of all,

observations
if radioiron

implications.
similar to

is to be cleared

the the

remains constant) can be obtained plasma iron concentration. This number of tissue receptors for or that erythropoiesis taken major
plasma

that of cold iron in patients, patient is to be measured, and diferric transferrin circulating patients plasma.

ie, if the true iron turnover of the the amount of labeled monoferric be made The identical to that in which in the this is been in an
a

has

been

altered

has

been up by objec-

must

but rather that is proportionately

measurements important it becomes

the amount of iron greater. Since the

is to characterize to separate the

manner

of ferrokinetic

erythrotrans-

achieved is unimportant described. In the present increase column

in saturation

and several suitable ways have study, in vitro tagging resulted

of 2% to 6%. Passage of iron through

ferrin
ity

effect

on turnover iron-the

from latter

the

intrinsic

marrow

capacity capac-

to assimilate
of the

reflecting

the functional

to remove

unbound

iron2

seems

unnecessary

and
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