Iron-Deficiency Anemia
Iron deficiency is used to designate a condition in which the total body iron
content has been depleted, no matter what the cause. Since body stores of iron must
be exhausted before red cell production is restricted, anemia is a late stage of iron
deficiency.
I. Prelatent iron deficiency
In the mildest stage, the reticuloendothelial iron stores are subnormal but there is
no biochemical evidence of deficiency. The only physiologic consequence of prelatent
deficiency is a compensatory increase in the rate of iron absorption.
II. Latent iron deficiency
It may be said to exist when iron stores are exhausted, but the blood hemoglobin
level remains above the lower limit of normal. In this stage, certain biochemical
abnormalities in iron metabolism are usually detected, such as an increase in free
erythrocyte protoporphyrin and a reduced plasma iron level.
III. Iron-deficient erythropoiesis
It refers to any situation in which red cell production is limited by the plasma iron
level. Such a limitation regularly occurs when transferrin saturation falls below 16%.
Stage
Normal
Prelatent
deficiency
Latent
deficiency
Early
iron-deficie
ncy anemia
Late
iron-deficie
ncy anemia
R-E* Iron
Stores
Normal
Reduced
Stages of Iron Deficiency
Plasma Iron
Anemia
Hypochromia
Microcytosis
Normal
None
None
Normal
None
None
Absent
Reduced
None
Usually none
Absent
Reduced
Mild to
moderate
In some cells
Indices normal
severe
Severe
Reduced MCV,
MCHC
Absent
Reduced
Other Features
-----Increased Iron
absorption
Increased
FEP*
*FEP: free erythrocyte protoporphyrin; R-E: reticuloendothelial.
-----Epithelial
changes
IRON METABOLISM
Distribution of iron in normal individuals
Protein
Hemoglobin
Myoglobin
Ferritin and
Hemosiderin
Transferrin
Enzymes
Total iron in
compound, mg
2500
140
100(males)
100-400(females)
3
-1
Function
O2 transport, blood
O2 transport, muscle
Storage
Transport
O2 utilization, etc.
The body of a normal adult man contains approximately 50mg iron per kilogram
of body weight, that of a woman contain 35mg/ kg. About two-thirds of this amount
is found in hemoglobin, and only about 3mg circulates in the plasma as transferrin, a
globulin. A very small proportion of the total body iron is present in myoglobin and
the hemeabsorbed. When there is increased need for iron, absorption may be more
efficient (10 to 20 percent). Iron derived from hemoglobin and other heme protein of
animal origin is absorbed as the intact heme molecule. Most other forms of iron must
be converted to ferrous iron in the stomach and duodenum in order to be absorbed.
Absorption is most efficient in the duodenum and upper part of the small intestine.
Iron is transported through the mucosal cell, but the exact mechanism is still
uncertain. The absorbed iron is then bound by plasma transferrin and transported to
the bone marrow for hemoglobin synthesis. The normal plasma iron level is 60 to 190
up per 100ml, but it is more useful to think of the serum iron in terms of percentage
saturation of transferrin, normally 20 to 45 percent. Iron turnover is rapid, so that 25
to 40mg iron is transported in the plasma per day. The great bulk of this transport is to
marrow erythroblasts. Since the total red blood cell mass contains approximately
2500mg iron and the red blood cell life span is 120 days, about 20mg iron is delivered
each day to the erythron. Conservation is the characteristic feature of iron metabolism.
The iron derived from the breakdown of hemoglobin joins the body pool and is used
again and again. Loss of iron from the body is minimal: probably about 1mg per day
in men and an average of 2mg per day in menstruating women. Most of this amount is
contained in cells desquamated from the intestinal mucosa or the skin. In women,
menstrual iron less is highly variable but, undoubtedly, is the greatest normal cause of
iron loss. A normal woman loses an average of 17mg iron during a normal period. The
loss of iron during a normal pregnancy is about 700mg, i.e. an average of about 2.5mg
per day.
CAUSES OF IRON DEFICIENCY
The possible factors loading to iron deficiency are
(l). insufficient iron in the diet.
(2). impaired absorption.
(3). increased requirements, and
(4). loss of blood.
In many instances, more than one of these factors is responsible for the resulting
deficiency. Except in infants and in rapidly growing children, chronic loss of blood by
hemorrhage is by far the most common cause of iron deficiency. Furthermore, the
nature of the diet itself other than its iron content, influences the absorption of iron.
Thus, both phosphates in the diet and phytates in cereals form a complex with iron
and reduce its absorption. Ascorbic acid favors iron absorption, probably by
promoting the reduction of ferric iron in food to the ferrous form.
The gastric hydrochloric acid favors ionization and thus absorption, yet many
persons are found in whom achlorhydria has existed for years without iron deficiency
developing.
CLINICAL MANIFESTATOINS
Most individuals with iron deficiency are asymptomatic. Pica (perverted appetite)
may be a striking manifestation, affected individuals macrave earth or clay
(geophagia), starch (amylophagia), or ice (pagophagia).
Abnormalities in epithelial tissues, including atrophic tongue, sore mouth,
angular stomatitis, thinning and spooning of the nails (keilenychia), or dysphagia,
may occur in an occasional patient who is iron-deficient. The plunner-vinson
syndrome (sideropenic dysphagia) is characterized by the feeling of food sticking in
the throat.
LABORATORY FINDINGS
Stages in the development of iron deficiency
Normal
Mild
Moderate
Severe
Hemoglobin
150g/L
130g/L
100g/L
50g/L
MCV
N
↓
↓
↓↓
MCHC
N
N
↓
↓↓
Marrow Fe Stores
Present
Absent
Absent
Absent
Serum Fe/TIBC
100/300
75/300
50/450
25/600
ug/100ml
Fe enzymes
N
N
N
↓
NOTE: MCV: mean corpuscular volume,
MCHC: mean corpuscular hemoglobin concentration,
TIBC: total iron binding capacity,
N: normal.
The anemia is hypochromic and microcytic. The percentage of reticulocytes is
usually normal but may increase temporarily following an acute episode of blood loss.
The bone marrow reveals moderate erythroid hyperplasia. Many of the late
normoblasts appear to have scanty cytoplasm.
Plasma and marrow iron
Normal
Iron deficiency anemia
Marrow hemosiderin
+,++
0
Marrow siderocyte (%)
20-90
0-15
Plasma ferrin (μg%)
100±60
<10-20
Plasma iron (μg%)
115±50
15-60
TIBC (μg%)
330±30
>360
Plasma iron saturation (%)
35±15
<15
RBC protoporphrin
20-40
100-600
(μg/100ml RBC)
Management
Every effort must be made to define the etiologic factor. This should be possible in
about 80 to 85 % of patients. In the remainder, it is possible that the underlying
disease is in remission; therefore, continued observation for new clues as to its nature
is warranted.
Once the etiologic diagnosis is made, appropriate treatment becomes possible.
Standard Therapeutic Oral Iron preparations
Preparation
Size
Iron Content
Usual Adult
Daily Dose
Ferrous sulfate
300mg
60mg
3 tablets
Ferrous gluconate
300mg
37mg
5 tablets
Ferrous
300mg
100mg
2 tablets
The following possible explanations for failure to respond to iron given orally
should be considered:
(1). incorrect diagnosis;
(2). complicating illness;
(3). failure of patient to take prescribed medication;
(4). inadequate prescription (dose or form);
(5). continuing iron loss in excess of intake, and
(6). malabsorption of iron.
Parenteral Iron Therapy
Iron-dextran complex and iron sorbitex, both of which contain 50 mg of iron per
ml of solution. The total dose of parenteral agents may be calculated from the amount
of iron needed to restore the hemoglobin deficit plus an additional amount to
replenish stores. One formula that allows for both is as follow.
Iron to be injected (mg)
= (15-patient’s Hb)× body weight× 3
(g / dl)
(kg)
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