Erythrocytes

ERYTHROCYTES (RED BLOOD CELLS)

RBC – 

• Non-nucleated biconcave disc.
• Mean diameter – 7.5 μm.
• Thickness – 2 μm at periphery.

• Process of RBC formation.

In early fetal life (up to 10 weeks) – 

• Occurs in yolk sac.

By third month of intrauterine life – 

• Moves to liver (major) & spleen.
• Chief site for erythropoiesis until 5 months of fetal life.
• Later in bone marrow.
• In children, 
• Blood formation occurs in most of bone marrow cavities.
• Gradual decrease of erythropoiesis in marrow of long bones.
• Gradual increase in marrow of flat bones.

At 20 years – 

• Only in flat bones of axial skeleton.
• Eg., Skull, vertebrae, ribs, sternum & pelvis.

Among long bones – 

• Only in proximal end of femur & humerus.

RBC LIFE SPAN:

• In adult – 120 days.
• Neonatal – 60-90 days.
• Fetal – 80 days (2/3rd of adult RBC lifespan)

ERYTHROCYTE DIFFERENTIATION:

• RBC on maturation undergoes series of differentiation.

Stages of development within bone marrow (sequentially) –

• Pluripotent hematopoietic stem cell.
• Multipotent stem cell.
• Unipotent stem cell.
• Pronormoblast.
• Early normoblast.
• Intermediate normoblast
• Late normoblast.
• Reticulocyte.
• After these stages, cell from bone marrow is released.
• Ultimately becomes an “Erythrocyte”/”Mature” RBC.
• Circulates in peripheral blood.

CHANGES IN RBC ON MATURATION:

• Reduction in cell size.
• Cytoplasm changes from basophilic to acidophilic.
• Nucleus disappears at reticulocyte stage.
• Because of extrusion in late normoblast stage.
• Hence, during excessive erythropoiesis (eg: erythroid hyperplasia of bone marrow), 
• Nucleated cells (immature cells) released into circulation.
• Hemoglobin appears at intermediate normoblast stage.
• Mitosis is most active & occurs up to intermediate normoblast stage.
• Late normoblast is not capable of mitotic division.

HEMOGLOBIN:

• Most important red cell constituent.

Hb molecule – 

• Consists of four globular protein.
• Each subunit has protein (polypeptide) part.
• I.e., Globin & nonprotein part (heme)
• Hence, each Hb molecule contains four heme units
• 2 pairs of globin 
• Ie., 4 polypeptide chains.
• Heme part of globular protein is same in all types of hemoglobin.

Protein part vary in different hemoglobin – 

• Adult hemoglobin (Hb A) – 
• Consists of 2 identical α-chains & 2 identical β-chains.
• Fetal hemoglobin (Hb F) – 
• 2 Identical α-chains & 2 identical γ-chains.
• Minor hemoglobin (HbA2) – 
• 2 identical α-chains & 2 identical δ-chains.

Adult blood – 

• About 96% HbA (α2 β2), 3-3.5% HbA2 (α2 δ2), & small amount of fetal Hb HbF (α2 γ2).
• Fetal Hb binds to 2-3 DPG less avidly than adult Hb.
• Hence, more oxygen affinity.
• Fetal Hb – Resistant to alkali denaturation.
• Alkali denaturation test (ADT) – Done to identify fetal Hb.

RBC DESTRUCTION:

• About 1% of RBC’s -Older & abnormal ones.
• Removed daily from circulation by macrophages.
• Mainly from spleen (major), liver & bone marrow.
• Inside macrophage, heme of hemoglobin is degraded to bilirubin.
• After iron removal.
• First heme is converted to biliverdin by heme oxygenase.
• Biliverdin is converted to bilirubin by biliverdin reductase.
• Certain metalloproteins (like zinc-or tin-porphyrins) – Used in jaundice.
• Helps decrease bilirubin production.
• By inhibiting enzyme heme oxygenase.