for B Sc MLT and MBBS students and BDS students. Pathology Hematology Lab Medicine Lab technology

1. Microcytic Hypochromic
Anemia: Iron Deficiency
DrI. Umme Habiba
Mbbs, Mphil, CHPE, FCPS registerar

2. Morphological types of Anemia
Anemia is defined as reduction in Haemoglobin
concentration below the normal for the age & sex.
Based on morphology & RBC indices
Microcytic Hypochromic
Normocytic Normochromic
Macrocytic

3. Microcytic Hypochromic Anemias
Iron Deficiency anemia
Thalassemias.
Sideroblastic Anemia.
Anemia of Chronic Disease/Anemia of inflammation.

4. Iron Deficiency Anemia

5. Significance of Iron
Iron is quantitatively the most bioactive element in
human enzymology with key roles in:
Oxygen transport & storage
Oxidative metabolism
Cellular growth & Proliferation

7. IRON CYCLE
Absorbed from gut.
 Bound to Plasma transferrin
Transported to marrow
Incorporated into haemoglobin
Mature RBCs released into circulation
After 120 days, ingested by macrophages, primarily in the spleen,
liver, and bone marrow. *
Iron is extracted from haemoglobin and
Recycled to plasma transferrin.

8. Equilibrium;
Iron absorbed from the gut is balanced by losses in
shed keratinocytes, enterocytes, and (in women)
endometrium.

9. Proteins of Iron transport & Storage
Transferrin: Single chain glycoprotein with two iron binding sites,
responsible for iron transport in plasma and extracellular fluid.
Transferrin Receptor: Transmembrane glycoprotein with two
transferrin binding sites.
Ferritin: Spherical protein of 24 subunits which binds 4500 atoms
of iron.
IRP: Four domain cluster protein which coordinates
translocational regulation of iron proteins.

10. Ferritin
Ferritin is a ubiquitous protein-iron complex.
Highest levels in liver, spleen, bone marrow & skeletal muscles.
In the liver, most ferritin is stored in the parenchymal cells.
Partially degraded protein shells of ferritin aggregate into
hemosiderin granules.
Since plasma Ferritin is largely derived from the storage pool of
body iron, its level correlates well with body iron stores.

12. Duodenal cytochrome B (Dcytb) is a reductase enzyme which
catalyzes the reduction of Fe3+ to Fe2+ in the process of iron
absorption in the duodenum.
The divalent metal transporter 1 (DMT1), also known as natural
resistance-associated macrophage protein 2 (NRAMP 2), and
divalent cation transporter 1 (DCT1), represents a large family of
orthologous metal ion transporter proteins.
The iron-responsive element-binding proteins, also known as
IRP
,IRE-BP
, IRBP and IFR ,bind to iron-responsive elements (IREs)
in the regulation of human iron metabolism.

13. Regulation of Iron Absorption: Hepcidin
 Liver is the source of this small peptide.
 Stimulus: Intrahepatic iron levels dictates Hepcidin synthesis.
 Role: Inhibits Ferroportin hence, inhibits Iron transfer from enterocyte into
the plasma.
 With Normal storage iron & erythropoietic activity; plasma hepcidin levels
are high. This leads to downregulation of ferriportin and trapping of most
of the absorbed iron, which is lost when duodenal epithelial cells are shed
into the gut.
 When body iron stores decrease or when erythropoiesis is stimulated,
hepcidin levels fall and ferriportin activity increases, hence allows a greater
fraction of the absorbed iron to be transferred to plasma transferrin.

14. Hephaestin
A ceruloplasmin homologue. implicated in
intestinal iron transport, Hephaestin is involved in
the metabolism and homeostasis of iron and
possibly copper.

15. Diseases that alter Hepcidin function
Anemia of Chronic Disease (ACD)
Mutations that Alter Its elaboration
Primary & secondary Haemochromatosis
Associated with mutation in Hepcidin
or gene regulating its expression,
Ineffective Erythropoiesis supresses Hepatic Hepcidin
production even when thestores are high (unknown
mechanism

16. Heme Proteins
Hemoglobin 70%
Myoglobin 5%
Tissue Specific Heme Proteins like:
Cytochromes
Oxygenases
Hydrolases
Peroxidase
Catalase
Ribonucleotide reductase
Aconitase

19. Storage Iron
Free Iron is highly toxic
Hence Iron is sequestered as
Ferritin or
Hemosiderin

20. Daily Iron Requirements
Males
 Daily basal iron loss
<1mg/day.
 10mg of Iron in diet with
10% absorption is sufficient
to maintain stores.
Females
 Menstruating: 1.5mg/day.
 Pregnant :2mg/day or
500mg for 280 days of
gestation

21. Causes of Iron Deficiency
 Nutritional:
 Decreased Dietary Intake.
 Increased Physiological Demand
Pregnancy
Lactation
 Iron Mal-absorption
 Blood Loss.

22. Causes of Blood Loss
Gartrointestinal
Pulmonary
(hemosiderosis)
Urinary
Hematuria
Hemoglobinuria
Uterine
(Menorrhagia)

23. Iron Deficiency in Children
 Most common between 1.5-4 years.
 Iron deficiency in children so important because of the possibility that
there maybe irreversible impairment of cognitive skills.

25. Anisocytosis in Iron Deficiency Anemia
It’s due to differences in availability of iron in different areas of
bone marrow.

26. Lab Diagnosis of Iron Deficiency Anemia

29. Iron Studies
 Serum Iron level:
60-170 mcg/dl
 Total Iron Binding Capacity (TIBC):
240 to 450 mcg/dl.
 Serum Ferritin:
Male: 12-300 ng/ml
Female: 12-150 ng/ml
**Ferritin level ˂ 12ng/ml indicates absence of iron stores.
 Iron Percent Saturation (% Saturation)

30. CBC findings
Hemoglobin (Hb):↓
Hematocrit (Hct)/Packed Cell
Volume (PCV):↓
Mean Cell Volume (MCV):↓
Mean Cell Hemoglobin
(MCH):↓
Mean Cell Hemoglobin
Concentration(MCHC):↓ or N
WBC Count: Total &
Differential; Normal*
Platelets: N or↑
Erythrocyte Sedimentation
Rate (ESR):
May be rapid depending
upon clinical status/ any
associated disease**

31. Peripheral Smear
RBC Morphology:
Aniso-poikilocytosis, Microcytosis and Hypochromia.
Pencil cells. Target cells.
NO NUCLEATED RBC (NRBC).
Reticulocyte count: Usually low for degree of
anaemia.

32. Iron Studies
Serum Iron: ↓
Serum Total iron binding Capacity (TIBC): ↑
Transferrin Saturation: ↓
Serum Ferritn: ↓
Serum Transferrin receptors: ↑
Haemoglobin Electrophoresis:
Normal HbA, HbA2 and HbF fractions*
* Iron deficiency can co-exist with β Thalassaemia Trait

33. Bone Marrow Examination
BM examination is not required for Diagnosis of IDA
If performed for some other indication may show;
Normal or slightly increased cellularity.
Mild Erythroid Hyperplasia.
Granulocytic and Megakaryocytic fractions usually normal.
Prussian Blue Iron stain (Perl’s stain); shows absence of
stainable iron in BM.

34. Key Points to remember:

35. More Pearls

36. Erythroid precursors possess high-
affinity receptors for transferrin,
which mediate iron import through
receptor-mediated endocytosis.