Iron is an essential mineral that is distributed throughout the body and is important for oxygen transport and cellular metabolism. Iron deficiency develops when requirements exceed supply and leads to iron deficient erythropoiesis and eventually iron deficiency anemia. It is one of the most common nutritional deficiencies worldwide, affecting toddlers, adolescent girls, pregnant women, and some minority groups. Treatment involves oral or parenteral iron supplementation depending on severity, with the goal of replenishing iron stores and repairing hemoglobin deficits.

1. Iron Deficiency Anemia
Imran Shahzad
Anjum,MD

2. Iron in human body
 Total Iron in human body averages 4 to 5 grams which is
distributed as:
1. 65% in form of Hb.
2. 4% in form of mayoglobin.
3. 1% in form of heme compunds whcih promote intracelluar
oxidation.
4. 0.1% is combined with protein transferrin in blood plasma.
5. 15%−30% stored for later use,mainly in reticuloendothelial
system of bone marrow and liver parenchymal cells,
principally in form of ferritin

3. Iron transport & metabolism
Fereitin hemosiderin
heme
Free Fe enzymes
(Tissue:liver & RNC of BM)
Transferrin−Fe
Macrophages
Degrading hemoglobin
Free Fe
Hemoglobin
Red cells
Blood loss−0.7mg
daily
In menses
Fe absorbed
(small intestine)
Only regulation
mechanism
Fe excreted−0.6mg
daily
Bilirubin
excreted

5. Iron absorption

6. Regulation of cellular & systemic Iron
homeostasis
hepcidin:25−amino acids peptide
hormone secreted by liver
Increase in Fe stores,
infection, inflammation
or malignancy
ferroportin: sole known cellular Fe
export channel
Fe deficiency,hypoxia,
increased erythropoiesis,
Ineffective erythropoiesis
Iron efflux into plasma from macrophages,
heptocytes
& intestinal enterocytes
+ −
− +
− +

7. Body Iron supply & storage

9. Iron deficiency
 Iron deficiency is a decrease in the amount of
body iron resulting from a sustained increase
in iron requirements over iron supply.
 Iron deficiency reduces the responsiveness of
erythroid progenitors to erythropoitein,apparently
through an Iron−aconitase−isocitrate pathway.
 with a lack of Iron, decreased utilization for RBCs
production helps preserve the supply of Iron for
vital functions in other tissues.

10. Epidemiology
 Iron deficieny is one of most prevalent forms of
malnutition and so most common anemia worldwide.
 Special groups:toddlers, adolescent girls, women of
child−bearing age and some minority groups.
 High prevalence of iron deficiency with or without anemia has
been reported among patients with restless legs
syndrome(akathisia).

11. Risk factors

12. Causes of Iron deficiency
 Increased Iron requirements &/or hematopoiesis
1. Growth
2. Pregnancy & lactation
3. Erythropoietin therapy
 Increased Iron loss/Blood loss
Gastrointestinal tract, Genitourinary tract, respiratory tract,
blood donation, phlebotomy as treatment for polychythemia
vera
 Decreased Iron intake or absorption
1. Dietary insufficiency of bioavailable Iron
2. Impaired absorption of Iron: intestinal malabsorption, gastric
surgery,Iron−refractory Iron deficiency anemia
3. Acute or chronic inflammtion

14. Presenting forms
1. no signs or symptoms coming to medical attention only
because of abnormalities noted on laboratory tests
2. features of underlying disorder responsible for
development of iron dediciency
3. manifestations common to all anemias
4. one or more of signs and symtoms considered highly
specific for iron deficiency,namely, pagophagia(variant of
pica), koilonychia and blue sclerae.

15. Clinical presentation
 It depends upon severity of Iron deficiency.
 It produce signs & symptoms common to all anemias which are
pallor, palpitations, tinnitus, headache, irritability, weakness,
dizziness, easy fatigability and other vague & nonspecific
complaints.
 Iron deficiency produce clinical symptoms independent of
anemia e.g. glosssitis, angular stomatitis, postcricoid
esophageal web or stricture, gastric atrophy.
 It has nonhematologic consequences, including impaired
immunity and resistance to infection, diminished exercise
tolerance and work performace and a variety of behavioral and
neuropsychologic abnormalities.

17. Laboratory evaluation of iron status
Direect measures Indirect measures
Fe
deficiency
Fe
overload
BM
Aspirate&
biopsy
MRI
Non−inv
Q.
Flebotomy
Liver biopsy
1. Serum ferritin
2. Serum iron &TIBC
3. Transferrin saturation
4. RBC protoporphyrin
5. Serum level of TRP
no single indicator or combination
of indicators is Ideal for evaluation
of iron status in
all clinical circumstances

19. Stages of Iron deficiency
 Negative iron balance/iron depletion: demands for
or loss of iron exceed the body´s ability to absorb
iron from diet and starts Iron store depletion.
 Iron deficient erythropoiesis: after the depletion of
Iron store,once transferrin saturation falls to
15−20%, Hb synthesis becomes impaired.
 Frank Iron deficiency anemia: both Iron store and
serum Iron depleted and Hb & hematocrit begin to
fall, reflecting iron deficiency anemia,transferrin
saturation at this poit is 10−15% with
hypochromia/microcitosis.

20. Classification of Iron deficiency
 un−complicated Iron deficiency:
the characteristic patterns of indicatores of body iron
status because hepcidin production is regulated only
by Fe−stores in a healthy person.
 complicated Iron deficiency:
the characteristic pattern of indicators of body iron
status is lost because hepcidin production is
controled by a lot of factors and serum ferritin acute
phase reactant.

21. Tests normal −ve IB IDE IDA
BM store 1−3+ 0 −1+ 0 0
S. ferritin (µg/dl) 50−100 <20 <15 <15
TIBC (µg/dl) 300−360 360˃ 380˃ 400˃
SI (µg/dl) 50 −150 NL <50 <30
Sat:SIx100/TIBC 30−50% NL <20 <10
Sideroblas%(BM) 40−60 NL <10 <10
Protoporfrin(µg/dl) 30−50 NL 100˃ 200˃
RBCs Morphology NL NL NL Micocytic/h
ipocromic
un−complicated iron deficiency

22. Pheripheral blood smear

23. Bone marrow aspirate

24. Assessment of Iron store on bone
marrow aspirate

25. un−complicated iron deficiency
 Transferrin saturation% : <18%
 Serrum ferritin : <15 µg/dl
 Red cell protoporphyrin level : 100 µg/dl˃
 Serum levels of TRP: 9 µg/dl˃
 RBCs morphology: microcytic/hypochromic
 Iron deficiency can give reactive thrombocitosis but
leukocyte normal.

26. Complicated iron deficiency
 Individualizied the patients because not have specific pattern of iron
depletion due to following reasons.
1. Depending upon clinical circumstances,the effects of inflammation or
erythropoiesis on hepatic hepcidin synthesis may predominate over those of iron
body stores.
2. Malignancy also stimulate hepcidin production.
3. Hypoxia and increased erythropoitic demand inhibit the stimulus.
4. Liver disease and malnutrition may also impair hepcidin expression.
5. Plasma ferritin:acute phase reactant, concentration increase by fever,acute
Infection, rheumatoid arthitis,liver & other tissue damge.
6. Only 2 conditions that may lower plasma ferritin concentration independtly of
decrease of iron stores are hypothyrodism and ascorbate deficiency.
serum TRP is less affected by inflammation, its measurement usually can determine
whether iron store are absent.

27. Differential diagnosis of microcytic
hypochromic anemia
 decreased body Iron stores
1. Iron deficiency anemia
 Normal or increased body iron stores
1. Anemia of chronic disease
2. Defective absorption,transport/use of iron
3. Disorders of globin synthesis: thalassemia, other
microcytic hemoglobinopathies
4. Disorders of heme synthesis: sideroblastic
anemias(hereditary & acquired)
5. Iron refractory,iron deficiency anemia
6. Atransferrinemia
7. Aceruloplasminemia
8. Divalent metal transporter hemochromatosis with impaired
iron export (type 4A)
9. Heme oxygenase 1 deficiency

28. Diagnosis of microcytic anemia
Tests Iron
def.
inflammati
on
thalassemia siderobla
stic
smear Micro/
hypo
Normal,mi
cro/hypo
Micro/hypo
with
targeting
variable
SI <30 <50 Normal−hig Norma−h
TIBC 360˃ <300 Normal normal
Saturation% <10 10−20 30 −80 30 −80
Ferritin(µg/dl) <15 30−200 50 −300 50 −300
Hb pattern norma normal abnormal normal

29. Diagnosis of microcytic anemia
 Diagnosis of Iron deficiency often is confirmed by outcomes of a
therapeutic trail of Iron.
 The unequivvocal diagnostic response consists of
1. A reticulocytosis,which begin approximately 3−5 days after adequate
Iron therapy is instituted, reaches a maximum on days 8 to 10 and
then declines.
2. Increase in Hb concentration which should begin shotly after
reticulocyte peak, is invariably present by 3 weeks after iron therapy is
begun and persists untill Hb concentation is restored to normal.
 Therapeutic trail merely aids in establishing presence of Iron
deficiency, search for underlying causes of iron deficiency must
continue despite a positive response to therapy.
 Difficulties in evaluation of microcytic hypochromic disorders
usually arise when direct assessment of BM iron is unavailable
and diagnosis depends on indirect indicators of Iron status.

31. Treatment of Iron deficiency anemia
 Generally iron therapy can be defered untill the underlying
cause of iron lack has been identified.
 The goal of therapy is to supply sufficient iron to repair Hb
deficit and replenish storage iron.
 For patients with unusual blood loss or malabsortion, specific
diagnostic tests and appropriate therapy take priority.
 Types of therapies: oral,parenteral,RBC tranfusion
 Types of therapies: oral,parenteral,RBC tranfusion
 Adverse reaction of therapies: hemochromatosis (iron overload)

32. Choice of therapy
 The severity and cause of iron deficiency anemia will determine
the appropriate approach to treatment.
 Oral iron is the treatment of choice for most patients because of
its effectiveness, safety and economy and should always be
given perference over parenteral iron for initial treatment.
 Parenteral therapy with risk of adverse reactions should be
reserved for exceptional patient who
1. Remains intolerant of oral iron despite repeated modifications in
dosage regimen.
2. Has iron needs that cannot be met by oral therapy because of
either chronic uncontrollable bleeding or other sources of blood
loss such as hemodialysis or coexisting chronic inflammatory
state.
3. Malabsorbs iron.
 Transfusion therapy is reserved for individuals who have symptoms of
anemia, cardiovascular instability, continued and excessive blood loss
from whatever source and require immediate intervention.

33. Oral Iron therapy
 Oral Iron preparations: ferrous sulfate, ferrous
fumarate, ferrous gluconate, polysaccharide iron.
 Therapy should begin with ferrous iron salt, ferrous
sulfate is most widely used either as tablets containing
60−70mg of iron for adults or as liquid preparation for
children.
 Taken separately from meals in 3 or 4 divided doses
and supplying a daily of 150 to 200 mg of elemental iron
in adults or 3 mg per Kg of body weight in children.
 Administration between meals maximize absorption.
 For milder anemia a single dose of 60mg per day may
be adequate.

34. Oral Iron therapy
 Sustained treatment for a period of 6−12 months
after correction of anemia will be necessary to
achieve stores of at least 0.5−1.0 g of iron.
 An increase in Hb concentration of at least 2 g/dl
after 3 weeks of therapy generally is used as
criterion for an adequate therapeutic response.
 Most patients are able to tolerate oral iron without
difficulty but 10%−20% may have symptoms
attributable to iron,most common side effects are
gastrointestinal.

35. Parenteral Iron therapy
 Parenteral preparations: higher and lower molecular weight
iron dextran, sodium ferric gluconate complex, iron sucrose
& ferumoxytol.
 Amount of iron need by an individual patient:
Body weight(kg)x2.3x(15−patient´s Hb,g/dl)+500 or 1000mg(for
store)
 Infrequent immediate life theatening anaphylactic reactions
constitute the most serious risk associated with use of either IM
or IV iron preparations,may have fatal outcomes.
 Delayed but severe serum sickness−like reactions may also
develop with fever, urticaria, denopathy, myalgias and arthralgias.

36. Red cell transfusion
 not only do transfusion correct anemia acuetly but
transfused red cells provide a source of iron for
reutilization,assuming they are not lost through
continued bleeding.

38. Bibliography
 Basic Principles & practice of Hematology
2013 by Hoffman
 Harrison´s principles of internal medicine
 Robbins Basic Pathology
 Guyton & Hall Text of Medical Physiology