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

Small Intestine

Plasma Transferrin

Bone Marrow

Erythrocytes

Reticulo-endothelial system Spleen/ Macrophages

Iron absorption

Iron metabolism RBC synthesis

Iron recycling RBC degradation

Ferritin

Hemoglobin

Liver

Ferritin

1

3

2

Plasma Transport 4

#1 Iron Absorption

Heme (Animal source) Hemin Iron

Heme oxygenase

Fe 3+ (Plant source)

Dietary substances

Fe2+

Ascorbate,Heme Phytates, Tea, Coffee

+

-

D-cytb

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

H+

Gut- Ferritin

Ferroportin

Fe2+

Fe3+

Hephahestin

Blood vessel Duodenal Lumen

Mucosal cell

#2 Iron Transport Liver

Transferrin synthesis

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)

Ferroportin

Fe2+

Fe3+

Hephahestin

Bone Marrow

#3 Iron Uptake and metabolism

TFRC

Uptake of TFRC-Transferrin complex

Clarthin

H+

Ferritin

Heme Ferrochetalase

Protoporphyrin IX

Hemoglobin

Bone marrow sinusoid

Normoblast

Mitochondira

#4 Macrophage recycling

Iron

Porphyrin

Globin

Amino-acids Bilirubin

Hepatocyte

Sinusoidal space

Macrophage (Kuppfer cells)

Transferrin Production

Bilirubin metabolism

Amino-acid metabolism

Pathogenesis of IDA

Dietary Iron Heme / Non-heme

Small Intestine

Plasma Transferrin

Bone Marrow

Erythrocytes

Reticulo-endothelial system Spleen/ Macrophages

Iron absorption

Iron metabolism RBC synthesis

Iron recycling RBC degradation

Ferritin

Hemoglobin

Liver

Ferritin

Plasma Transport

Reduced intake - Inadequate diet - Increased requirement Reduced absorption

Increased iron loss - Blood loss

Inadequate transport Atransferrinemia Anti-transferrin Ab

Etiologies of IDA

Reduced intake / absorption

Inadequate diet 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

Increased loss

Gastrointestinal loss 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%

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 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