Iron Deficiency Anemia &Recent Advances In Iron Metabolism
Dr. Siddartha. K
Moderator : Dr. Faiq Ahmed
Dept Of Lab Medicine
Basavatarakam Indo American
Hospital And Research Institute
Defined as an insufficient RBC mass to
adequately deliver oxygen to peripheral
Defined as a decrease in the amount of red
blood cells (RBCs) or the amount
of hemoglobin in the blood. It can also be
defined as a lowered ability of the blood to
Anemia is defined as a reduction of the total
circulating red cell mass below normal limits
Iron deficiency is the most common
nutritional deficiency in both developing and
Full-term infants - 75 mg/kg body weight of Fe.
Adult male - 50 mg/kg body weight of Fe.
Adult women – 35 mg/kg body weight of Fe.
In the average subject, the plasma iron
concentration is ∼18μmol/L (100 μg/dl), and
the TIBC is ∼56 μmol/L (300 μg/dl).
Thus, only about one third of the available
transferrin binding sites are occupied, leaving a
large capacity to deal with excess iron.
Plasma iron concentration varies over the
course of the day, with the highest values in the
morning and the lowest in the evening.
Levels of serum transferrin are more constant
Iron is not actively excreted from the body;
Eliminated only through the loss of
¶ Epithelial cells from the GIT,
¶ Epidermal cells of the skin, and,
¶ In menstruating women, red blood cells.
Ferroportin - also expressed in other tissues
• Macrophages recycling iron from old RBC,
• Hepatocytes storing iron, and
• Placental trophoblast delivering iron from
mother to fetus
A small proportion of the heme iron may pass
into the plasma heme exporter protein FLVCR
(feline leukemia virus, subgroup C
receptor), which transfers heme onto a
heme-binding protein, hemopexin.
Dietary heme iron – unaffected by diet
Dietary non-heme iron
Enhanced by Vit C, keto sugars, organic
acids, and amino acids.
Decreased by phytates, polyphenols,
calcium, tannates in tea, bran.
Hepcidin, the liver-expressed antimicrobial
Type II acute-phase reactant produced in the
liver that displays intrinsic antimicrobial
Acts as a systemic regulator of iron
Produced in the liver, secreted into the
plasma, and excreted through the kidneys.
Intracellular iron levels in enterocytes (and
most other cells) are sensed by two iron-
regulatory proteins (IRP1 and IRP2).
Intracellular iron concentration is modulated
by IRP binding to IREs ???
IRP1 contains a 4Fe•4S cluster ,when
saturated with iron, converts IRP1 to a
cytosolic aconitase .
In this enzyme form, IRP1 has low affinity for
IREs in transferrin mRNAs.
When iron-poor, IRP1 loses its aconitase
activity and greatly increases its affinity for
Transferrin – plasma iron binding protein
Synthesized in the liver, but lesser amounts
are made in other tissues, including the
central nervous system, the ovary, the testis,
and helper T lymphocytes.
Transferrin keeps iron nonreactive in the
circulation and extravascular fluid,
Delivers iron to cells bearing transferrin
Transferrin binds 2 atoms of trivalent (ferric)
Fe3+ binds to transferrin with very high
The affinity of iron–transferrin interaction is
pH-dependent, decreasing as pH is lowered.
Metals like Cu,Cr,Mn,Ga,Al,Co also bind to
transferrin but with less affinity than iron.
2 receptors TfR1 and TfR2
TfR1- have more affinity for diferric
TfR2- binds transferrin with lower affinity
Max receptors are present in
epithelial antigen of
the prostate 3 =
∼80% to 90% of the Fe is incorporated into heme.
Rest is stored as ferritin.
Because excess heme is toxic to cells
Erythroblasts also express heme exporter FLVCR
and iron exporter ferroportin.
FLVCR functions as a safety valve to prevent
accumulation of excess heme early during
feline leukemia virus subgroup C
RE system (macrophages)
2 phases are seen
Early phase (with in hrs after Erythrophagocytosis )
Later phase (period of yrs)
The early phase - sequential induction of
ferroportin mRNA expression iron release
Later phase – in iron demand
MCV,MCH,MCHC are decreased
RDW is high
Serum ferritin ≤12 ng/ml (sensitivity -25%)
and improved to 92%, by using a
diagnostic cutoff value of ≤30 ng/ml.
Increased sTfR has been reported to be an
indicator of iron deficiency - released by
erythropoietic precursors in proportion to
their expansion, and is not increased by
N = 15–300 μg/l in healthy men
2.Immuno assay system
High concentrations of serum ferritin, may
also be found in patients with liver disease,
infection, inflammation, or malignant
disease, aging, juvenile rheumatoid arthritis,
leukemia, and Hodgkin's disease.
N values in women 16.1 ± 7.4 μmol/l.
in men 18.0 ± 6.3 μmol/l.
Methods : -
With protein precipitation
With out protein precipitation
The normal serum TIBC was
68.0 ± 12.6 μmol/l in women and
63.2 ± 9.1 μmol/l for men.
Increased in IDA and pregnancy.
Normal or decreased in anemia of chronic
disease or sideroblastic anemia.
Decreased in pathological iron overload.
Normal values – 0.63-1.80 g/l
1 mg of transferrin binds 1.4 μg of iron
Ratio of the serum iron conc. and the TIBC
expressed as a percentage
in men 29.1 ± 11.0%;
in women 24.6 ± 11.8%
Serum iron concentration (μmol/l) divided by
the transferrin concentration (μmol/l).
Better precision than the TSAT and showed
greater specificity for detecting iron
overload than the transferrin saturation
sTfR conc. are high in
neonates and decline until
adult conc. are reached at
During pregnancy sTfR
levels increase, returning
to nonpregnant values 12
weeks after delivery.
The “free” protoporphyrin conc.(Zn
protoporphyrin) of RBC increases in iron
Reticulocyte count will be low in IDA
CHr – measures the Hb content of
Directly reflects the recent Hb synthesis in
bone marrow precursors.
Greater sensitivity(100%) and specificity(80%)
for diagnosing Iron Deficiency Anemia.
Normal values – 24.5- 31.8 pg.
Normal iron stores with iron
granules in erythroblasts
Absence of iron stores in IDA
Dacie and Lewis: PRACTICAL HAEMATOLOGY tenth editon.
Clinical laboratory hematology by McKenzie
Robbins and Cotran pathological basis of disease 9th edition