IRON DEFICIENCY ANAEMIA

1. IRON DEFICIENCY ANEMIA
DR ARUN SRIVASTAVA
MD DCH
ASSOCIATE PROFESSOR
COMMUNITY MEDICINE
BRD MEDICAL COLLEGE ,GORAKHPUR

2. • Iron is required by cells for multiple functions
including DNA synthesis, oxygen transport and
cellular energy synthesis. Various iron
containing proteins are hemoglobin,
myoglobin ,cytochrome c, cytochrome 450,
catalase, myeloperoxidase cycloxygenase , and
ferritin lipoxygenase

3. • . Certain enzymes are iron dependent
aldehyde oxidase, NADP DEHYDROGENASE,
tyrocin hydroxylase,
succinate dehydrogenase, tryptophan
hydroxylase, tryptophan hydrolase, xanthine
oxidase, ribonucleotide reductase,

4. • Heme Iron is not affected by presence of any
factors in the gut . The absorption of non
heme iron is retarded by an alkaline pH,
presence of phosphates, phytates, bran,
starch, tannins, calcium, antacids and other
metals like Cobalt and lead.

5. • Non-heme iron absorption is enhanced by
ascorbic acid free hydrochloric acid, presence
of sugar, amino acids in the diet, presence of
heme iron i.e. non vegetarian source of iron
and EDTA.

6. • Phytates which constitutes 1 to 2% of many
cereals, nuts and legumes play a major role in
the causation of nutritional anaemia in the
developing world

7. • Bioavailability of iron from a particular dietary
source affects the amount absorbed. Ferrous
ion is better absorbed compare to ferric iron.
It is estimated that in wheat based diet iron
absorption is around 2% and in rice based diet
it is 5 to 13%.

8. • Poor bio-availability of iron in large cereal
based diet is a major cause of iron deficiency
anaemia in most developing countries. Fish
meat and poultry are good sources of iron and
bioavailability is around 20 to 30%. Calcium in
the form of milk , cheese or calcium added to
the bread depresses iron absorption.

9. • Major regulation of iron cycle occurs through
control of ABSORPTION since there is hardly
any excretion via physiological mechanism.
Iron is available in the ferric form in the diet.
This is reduced to ferrous form by the
duodenal cytochrome B reductase in the
lumen of proximal small intestine.

10. The iron molecule that is taken into the mucosal
cell across the brush border binds either with
the apoferritin molecule when iron is status is
adequate or with the transferrin when iron is
required by the body

11. • The transferrin bound iron is then released to
the ferroportin at the basolateral membrane
to be transported across into the circulation.
Also simultaneously ferrous iron has to be
oxidised to ferric state again during baso
lateral membrane transfer and this occurs
through the multi copper fero oxidase
hephaestin

12. • It again binds to transferrin in circulation to
be transported to various sites of synthesis of
iron containing proteins and enzymes. Iron
bound to apo ferritin remains in the mucosal
cell and gets denuded with the cell within 3 to
4 days.

13. • If iron is required in the body it is bound to the
feroportin, which is then transferred to the
the transferrin ( produced in the liver )which
carries it across the mucosa. It is then utilised
in the bone marrow for hemoglobin
production, in the muscle tissue for myoglobin
and in the body for various other enzymes.
Any excess of iron is stored in the form of
ferritin in the liver

14. Role of hepcidin
• There is no excretory mechanism for iron in
the body. Absorption is regulated at the
cellular and systemic level hepcidin A25 amino
acid hormone synthesized in the liver, is
responsible in balancing the enterocytes as
well as the macrophage release of iron to
maintain iron homeostasis.

15. • Hepcidin inhibits the absorption of iron at the
intestinal level through internalizing
ferroportin the key molecule for transporting
the iron in the ferrous form across the brush
border of the intestinal villi. Thus it blocks the
binding of ferroportin to the iron molecule
and prevents absorption. Also it prevents
release of iron through the same mechanism
at the level of of storage level in the
macrophages.

16. • TMPRSS6 (liver express type 2 transmembrane
serine protease) normally inhibits hepcidin
through cleaving of bone morphogenetic
protein i.e. BMP co receptor hemojuvelin. In
vitro TMPRSS6 expression is upregulated by
hypoxia and iron deficiency.

17. • However one of the genetic variants of
TMPRSS6 leads to the downregulation of the
inhibition of hepcidin this causes and
overexpression of hepcidin and therefore
inhibition of iron absorption causing a
refractory iron deficiency state .
•

18. • Iron cycle in the body RBC circulate for their
life span of approximately 120 days and are
then destroyed in the spleen liberating free
iron which is generally transported to the
bone marrow and other tissues for
its reutilization

19. • Thus most of the iron is recycled continuously
in the body with only 1 to 1.5 mg/day of iron
being excreted through the intestinal
epithelial cell after completion of their life
span . Since 10% of ingested iron is absorbed
and the daily loss is only 1 to 1.5 mg so one
needs to ingest about 10 mg of iron daily
except during periods of extra needs.

20. Food containing iron
• Food rich in iron are green leafy vegetable
,jaggery, cereals , especially ragi, dates,
almond, nuts, sprouts. Non vegetarian sources
such as pork, veal and other red meats
especially liver. Though breast milk contains a
small amount of iron the bioavailability of this
iron ( lactoferrin ) is about 50 to 70% and
hence it is adequate for the first four to six
months of life

21. Iron losses
• Total daily iron loss of an adult is probably 1
mg and about 12.5 mg per 28 day cycle in
menstruating women. Major routes of iron
losses are through hemorrhage i.e. where ever
blood is lost, iron is lost. The cause of which
may be physiological that is menstruation,
childbirth or pathological like hookworm,
malaria, hemorrhoid, peptic ulcer.

22. IRON LOSSES
• The second is Basal losses such as excretion
through the urine, sweat and bile and
desquamated surface cells. The widespread use
of IUDs in the family planning program is an
additional cause of iron loss. IUDs have been
shown to increase the average monthly blood
loss by between 35 and 146% depending upon
the type of the device. Hormonal contraceptive
on the other hand decreases menstrual blood
loss by about 50%.

23. • Three stages of iron deficiency have been
described.
A. First stage characterized by decrease
storage of iron without any other detectable
abnormality.
B. An intermediate stage of latent iron
deficiency i.e. iron stores are exhausted but
anaemia has not occurred as yet . Its
recognition depends upon measurement of
serum ferritin level.

24. • The percentage saturation of transferrin falls
from a normal value of 30 % to less than 15%.
this stage is most widely prevalent stage in
India.
C. The third stage is that overt iron deficiency
where there is decrease in the concentration
of circulating hemoglobin due to decreased
hemoglobin synthesis.

25. Epidemiology of iron deficiency
anaemia
It is estimated that iron deficiency affects about
30% of the world population and about 70 to
90% in the developing countries including India.
IDA is most common in the age group of 6 to 3
years and 12 to 17 years adolescence.
It is also significantly common among pregnant
and lactating women does compromising the iron
stores in their infants. IDA can occur due to
decreased absorption and increased demand for
high losses from body

26. • WHO expert group proposed anaemia or
deficiency should be considered to exist when
hemoglobin level is below the following levels
in different groups like in adult males if the
level is below 13g/dl adult female non
pregnant 12 g/dl adult female pregnant
11g/dl children 6 months to 6 years 11g/dl
and children 6 to 14 years 12g/dl.

27. • At all ages the normal MCHC should be 34%.
Value below that indicates that red cells are
hypochromic which occurs in iron deficiency
anaemia so hemoglobin level of 10 or 11mg/dl
has been defined as early anaemia. A level
below 10 g/dl as marked anaemia.

30. Clinical manifestations
• Clinical features of IDA are similar to those
due to anaemia of any etiology. However
besides anemia, iron deficiency affects a
number of other systems in the body these
include neurotransmitters causing cognitive
dysfunction epithelial tissues, etc . Children
with IDA generally present with symptoms
depending on the rate of fall of haemoglobin
and homeostatic adjustment of various
systems in the body.

31. • As the fall of hemoglobin is very gradual the
onset of symptoms is insidious. Initially pallor
noticed over tongue, lips conjunctiva, palms
,nails etc, easy fatigability ,anorexia and
irritability may be noticed
•

32. • Hyperdynamic circulation may lead to
palpitation, shortness of breath, decreased
exercise tolerance and CHF. Mild degree of
hepatosplenomegaly is also not uncommon.
Pedal edema in IDA may be due to congestive
heart failure, impaired renal function or
associated protein deficiency. Rarely increased
intracranial tension with papilledema may
occur.

33. • . Skull changes with caput quadratum
appearance ( frontoparietal bossing) similar to
that seen in congenital hemolytic anaemia,
may be seen in children with chronic long
standing iron deficiency occurring since early
life. Skeletal changes do not reverse with iron
therapy.

34. Non hematologic consequences of iron
deficiency
• Koilonychia and Plati-nychyia, glossitis
stomatitis and angular cheilosis are the other
common features not commonly seen in
children. Formation of mucosal webs at the
Pharyngo-oesophagial junction causes
dysphagia mainly for solids.

35. • The triad of dysphagia due to esophageal
webs, koilonychia and splenomegaly in a
patient with IDA is known as Plummer Vinson
Or Paterson Kelly syndrome.

36. • Pica is a well documented features of anaemia
in children. Craving to eat unusual substances
such as dirt, clay , ice, salt, cardboard etc. It is
seen almost 70 to 80% of the patients.

37. Evaluation of iron status
First hemoglobin concentration is a relatively
insensitive index of nutrient depletion. Its
value is less in population group in which
anaemia is not serious i.e. because anaemia is
a late manifestation of iron deficiency which
can frequently occur without the
manifestation of anaemia

38. Serum iron
• This is a more useful index then hemoglobin
concentration. The normal ranges 0.80 to 1.80
mg /litre values below 0.5 mg/litre indicates
probable iron-deficiency.

39. Serum ferritin
• The single most sensitive tool for evaluating iron
status is by measurement of serum ferritin it
reflects the size of iron stores in the body. It is the
most useful indicator of iron status in a
population where the prevalence of iron
deficiency is not high. Values below 10 microgram
per litre probably indicate an absence of stored
iron
• Serum transferrin saturation this should be
above 16 % normal value is 30 %

40. TOTAL IRON BINDING CAPACITY AND
TRANSFERRIN SATURATION
• Total iron binding capacity (TIBC) is the
measure of plasma transferrin which is free
,not bound to iron. The normal value of TIBC is
250 to 350 mcg/dl. Iron deficiency state TIBC
is increased 350mcg/dl and transferrin
saturation is reduced to to below 16 %( below
12% for children). TIBC less than 200
mcg/dl is characteristic of inflammatory
disease. Factor that affects serum iron
concentration do not alter values of TIBC.

41. • Serum ferritin children sensitive laboratory
index of iron status. It is best non invasive test
gold standard with high specificity and
adequate sensitivity for evaluating iron status
in the body. A comparative value of less than
12 NG per ml is highly specific for iron
deficiency but gives no information about its
magnitude.

42. • Serum ferritin is increased in chronic disorders
like chronic infection and inflammation
malignancies chronic liver disorders presence
of any of these coexisting IDA can be missed

43. TREATMENT
• Basic principles of management include
correction of anaemia and treatment of
underlying cause. Treatment of IDA depends
upon severely and associated complications.
Those with very severe anaemia and CHF with
hemoglobin less than 5 g/dl require
hospitalization. Oral iron therapy with
monitoring is adequate for those without
evidence of CHF .

44. • . Packed red blood cell ( PRBC) transfusion is
required for those in CHF irrespective of the
level of of HB. Packed red cell at 5 ml per kg
should be slowly administered over 2 to 3
hours to avoid volume overload.

45. Medicinal iron therapy
Iron therapy is the ideal treatment for IDA. it
is safe, economical and as effective as
parenteral therapy. For infants and children
the recommended therapeutic dose is 3 to 6
mg of elemental iron per kg body weight/ day.

46. • . Higher doses are unnecessary and may
increase side effects reducing patient
compliance. Although the desired hemoglobin
level is usually reached in 2 to 3 months. Iron
therapy should be continued for another 2 to
3 months to build up iron stores.

47. THANKS
• .