7. PROCESS OF HEMOPOIESIS

PROCESS OF HEMOPOIESIS

HEMOPOIESIS: Around 250 billion (25 × 10¹⁰) new RBCs, 20 billion (20 × 10⁹) new WBCs, and 25 billion (20 × 10⁹) platelets are required for replacing aged or dead cells each day. Formation of blood cells (RBCs, WBCs, and platelets) is termed as haemopoiesis or haematopoiesis, and the tissues involved are known as haematopoietic tissue.

ERYTHROPOIESIS

Formation of RBCs is known as erythropoiesis.

Steps of Erythropoiesis

1. Division of pluripotent stem cells to yield multipotent myeloid progenitor cells.
2. These cells develop into erythrocyte colony-forming cells (CFU-E) in the presence of growth factors.
3. Erythropoietin (EPO) along with other growth factors promotes production of proerythroblasts (pronormoblasts).
4. Proerythroblasts give rise to smaller daughter cells through series of cell divisions:
   • Basophilic erythroblasts (early normoblasts)
   • Polychromatic erythroblasts (intermediate normoblasts)
   • Orthochromatic erythroblasts (late normoblasts)
5. Cells become reticulocytes as their nuclei are lost.
6. Reticulocytes are released into circulation and mature into erythrocytes in 1-2 days.

LEUCOPOIESIS

Formation of WBCs is known as leucopoiesis. All different kinds of WBCs are obtained from haematopoietic stem cells in the bone marrow.

Origin of Different WBCs

• Neutrophils and Monocytes: Originate from myeloblasts and monoblasts (from granulocyte and monocyte colony-forming cells).
• Eosinophils and Basophils: Originate from eosinophil and basophil colony-forming cells respectively.
• Lymphocytes: Develop from bone marrow stem cells; lymphoblasts undergo cell divisions to form prolymphocytes, which mature into lymphocytes.

THROMBOPOIESIS

Formation of platelets is known as thrombopoiesis.

Mechanism of Thrombopoiesis

• Megakaryoblasts (15-20µm diameter) are the precursor cells of platelets.
• Megakaryocytes are giant cells with large irregular nucleus; they are polyploid cells.
• Their cytoplasm contains mitochondria, rough endoplasmic reticulum, and Golgi complex.
• Thrombopoietin (TPO) – hormone secreted by liver, kidneys, and skeletal muscles – controls maturation of megakaryocytes and platelet production.

FORMATION OF HAEMOGLOBIN

Haemoglobin (Hb) is a respiratory pigment present in RBCs, giving them their red colour. It is a conjugated protein having 4% heme (Fe²⁺ and porphyrin) and 96% globin protein. It is synthesised within immature erythrocytes during erythropoiesis in the red bone marrow.

Normal Level of Haemoglobin in Human Body

• Adult males: 14-17 gm/dL
• Adult females: 12-15 gm/dL
• Newly born babies: 14.5-18.5 gm/dL

Note: Age, sex, altitude, exercise, excitement, and adrenaline level affect Hb level in blood.

Structure of Haemoglobin

• Heme: Cyclic tetrapyrrole with four pyrrole molecules; gives red colour to RBCs. Contains methyl (M), vinyl (V), and propionate (Pr) groups.
• Globin Chains: Each adult haemoglobin (Hb-A) molecule consists of 4 globin chains: 2 α (α₁ and α₂) and 2 β (β₁ and β₂) chains. These 4 chains form 2 dimers (α₁β₁ and α₂β₂).

Synthesis of Haemoglobin

1. Succinyl-CoA and glycine condense to form 5-aminolevulinic acid in the mitochondrion.
2. Succinyl-CoA forms a pyrrole molecule by binding with glycine.
3. 4 pyrrole molecules combine to form protoporphyrin IX.
4. Protoporphyrin IX combines with iron to form the heme molecule.
5. Each heme molecule combines with globin (a long polypeptide chain synthesised by ribosomes).
6. This forms a subunit of haemoglobin – a haemoglobin chain (molecular weight ~16,000).
7. 4 of these chains loosely combine to form a complete haemoglobin molecule.