Microcytic Hypochromic

Anemias

Microcytic Hypochromic anemias

Disorders of Heme Synthesis
Iron Deficiency Anemia

Disorders of globin Synthesis

Thalassemia

Anemia of Chronic disease

Sideroblastic Anemia
Lead Poisoning

Iron deficiency anemia

Most prevalent nutritional disorder in the world
Common in adolescent girls and women in child
bearing age

Iron Cycle
Dietary Iron
Heme / Non-heme
Iron absorption

Small Intestine
Plasma Transport

Plasma Transferrin

Iron recycling
RBC degradation

Liver
3

Bone Marrow

Iron metabolism
RBC synthesis

Ferritin

Ferritin
Erythrocytes
Hemoglobin

Reticulo-endothelial system
Spleen/ Macrophages

#1 Iron Absorption
Dietary substances
Duodenal Lumen

Heme
(Animal source)

Hemin

Heme oxygenase

Mucosal cell

Blood vessel

Iron

Fe 3+
(Plant source)
Ascorbate,Heme
Phytates, Tea, Coffee

Fe2+
+
-

Ferroportin

Dcytb

Fe2+
H+

Hepha
hestin

DMT 1

DMT 1 : Divalent metal ion transporter

Proton Symporter
DMT 1 level increases in iron deficient state
(Reduced levels of stored iron)
? When erythropoiesis is ineffective
Hepcidin degrades ferroportin

Fe3+
GutFerritin

#2 Iron Transport

Liver

Fe2+
Ferroportin
Hepha
hestin

Transferrin
synthesis
Fe3+

Bone Marrow

Transferrin Levels increase when iron

stores are depleted
Most Circulating Iron is bound to
Transferrin
Iron-binding sites in Transferrin keep it
saturated.
Level of unsaturated sites determine
Total Iron Binding capacity (TIBC)

#3 Iron Uptake and metabolism

Bone marrow sinusoid

Uptake of
TFRC-Transferrin complex

Normoblast

TFRC
Clarthin
H+

Protoporphyrin IX

Ferritin
Heme
Hemoglobin

Ferrochetalase

Mitochondira

#4 Macrophage recycling

Macrophage
(Kuppfer cells)

Globin

Iron
Porphyrin

Amino-acids

Bilirubin

Sinusoidal space
Hepatocyte

Amino-acid metabolism
Transferrin
Production

Bilirubin metabolism

Pathogenesis of IDA
Dietary Iron
Heme / Non-heme
Inadequate transport
Atransferrinemia
Anti-transferrin Ab
Plasma Transport

Reduced intake
- Inadequate diet
- Increased requirement
Reduced absorption

Iron absorption

Small Intestine

Plasma Transferrin
Iron recycling
RBC degradation

Liver
Bone Marrow
Iron metabolism
RBC synthesis

Ferritin

Reticulo-endothelial system
Spleen/ Macrophages

Ferritin
Erythrocytes
Hemoglobin

Increased iron loss

- Blood loss

Etiologies of IDA
Reduced intake / absorption
Inadequate diet

Increased loss
Gastrointestinal loss

RDA men 5-10mg/d

RDA women 7-20mg/d

Reduced absorption

Achlorhydria
Gastric surgery
Duodenal bypass
Tannin / Phytates, Bran

Increased demand
Infancy
Pregnancy
Lactation

Neoplasms
Parasites
Varices
Ulcerations

Excessive menstrual flow

Neoplasms
Epistaxis
Coagulopathies

Stages in iron deficiency

1. Depletion of Iron stores (Pre-latent IDA)

Hepatocytes, macrophages, liver, spleen

Bone marrow iron stores depleted
Serum ferritin reduced
Fatigue, malaise in some patients

2. Alterations in transport proteins (Latent IDA)

Transferrin saturation declines, TIBC increases

3. Iron deficiency anemia

Reduced hemoglobin
Microcytic hypochromic RBCs

Clinical features
Fatigue
Reduced neuromuscular performance
Epithelial tissue defects

Koilonychia
Glossitis, angular stomatitis
Sideropenic dysphagia (Plummer wilson syndrome)
Esophageal webs

Pica
Pagophagia, food-pica (brittle foods), non-food substances

Impaired growth and development

Lab diagnosis: Blood counts

Normal

Iron def.

Hb

12-14 g/dl

< 10

PCV

45%

<30%

MCV fl

80-96

< 80

MCH pg

27-33

< 25

MCHC %

33-37

< 27

PS

NC, NC

uC, HC

Retic

N/decreased

RDW

Normal

Increased

WBC& PLT

N/increased

Blood film:
Red cells are microcytic and
hypochromic
Anisocytosis and poikilocytosis
seen
In
addition
to
poorly
haemoglobinized red cells,
elliptocytes(pencil
cells),tear
drop cells,cell fragments are
present

Lab diagnosis: Iron studies

Normal

IDA

S.ferritin

50-300 ug/l

<15ug/l

S.Iron

50-150 ug/dl

10-15 ug/dl

TIBC

310-340 ug/dl

350-450 ug/dl

Transferin
saturation

30-40%

< 15%

RBC
protoporphyrin

30-50 ug/dl

> 200 ug/dl

BM iron

nil

Lab diagnosis: Bone marrow

Bone marrow findings
Hypercellular
Erythroid hyperplasia;
reversal of M:E
Micronormoblastic
reaction smaller,
persistent basophilia
Myelopoiesis and
megakaryopoiesis N
Depleted marrow iron
grade 0

Differential diagnosis

Thallassemia (TIBC , S.iron )

Anemia of chronic disorders (hypo microcytic)
Sideroblastic anemia (S.iron, pappenheimer)
Lead poisoning (basophilic stipling, blue line on
gums)

Response of IDA to Iron therapy

Resolution of constitutional symptoms (within 7
days)
Increase in Reticulocyte count (within 5-10 days)
Increase in RDW (2-3 weeks)
Normalization of hemoglobin (2 months)
Normalization of microcytosis (2-3 months)
Resolution of glossitis (3 months)
Resolution of koilonychia (3-6 months)

Anemia Of Chronic disease

Impaired red cell production a/w chronic
diseases (chronic infections,immune
diseases,neoplasm)
Role of inflammatory mediators (IL-6) leading
to increased hepcidin production
Erythroid precursors starved for iron in midst
of plenty!!!(low S. iron, reduced TIBC, and
abundant stored iron)
Reduced EPO,decreased survival of RBCs