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
