ERYTHROPOIESIS

 DEFINITION:

   Erythropoiesis is the process of the origin, development and maturation of erythrocytes. Hemopoiesis or hematopoiesis is the process of origin, development and maturation of all the blood cells.

SITE OF ERYTHROPOIESIS:

IN FETAL LIFE

 in fetal life, the erythropoiesis occurs in three stages. 

1. Mesoblastic Stage

During the first 2 months of intrauterine life, the RBCs are produced from mesenchyme of yolk sac.

2. Hepatic Stage

From third month of intrauterine life, liver is the main organ that produces RBCs. Spleen and lymphoid organs are also involved in erythropoiesis.

3. Myeloid Stage

During the last 3 months of intrauterine life, the RBCs are produced from red bone marrow and liver.

IN NEWBORN BABIES, CHILDREN AND ADULTS

  in newborn babies, growing children and adults, RBCs are produced only from the ted bone marrow. 

1. Up to the Age of 20 Years                                 RBCs are produced from red bone marrow of all bones (long bones and all the flat bones).

2. After the Age of 20 Years

RBCs are produced from membranous bones like vertebra, sternum, ribs, scapula, iliac bones and skull bones and from the ends of long bones. After 20 years of age, the shaft of the long bones becomes yellow bone marrow because of fat deposition and loses the erythropoietic function.

In adults, liver and spleen may produce the blood cells if the bone marrow is destroyed or fibrosed. Collectively bone marrow is almost equal to liver in size and weight. It is also as active as liver. Though bone marrow is the site of production of all blood cells, comparatively 75% of the bone marrow is involved in the production of leukocytes and only 25% is involved in the production of erythrocytes.

  But still, the leukocytes are less in number than the erythrocytes, the ratio being 1:500. This is mainly because of the lifespan of these cells. Lifespan of erythrocytes is 120 days whereas the lifespan of leukocytes is very short ranging from 1 to 10 days. So, the leukocytes need larger production than erythrocytes to maintain the required number.

PROCESS OF ERYTHROPOIESIS

STEM CELLS

Stem cells are the primary cells capable of self-renewal and differentiating into specialized cells (Chapter 1). Hematopoietic stem cells are the primitive cells in the bone marrow, which give rise to the blood cells.

Hematopoietic stem cells in the bone marrow are called uncommitted pluripotent hematopoietic stem cells (PHSC). PHSC is defined as a cell that can give rise to all types of blood cells. In early stages, the PHSC are not designed to form a particular type of blood cell. And it is also not possible to determine the blood cell to be de veloped from these cells, hence, the name uncommitted PHSC . In adults, only a few of these cells are present. But the best source of these cells is the umbilical cord blood.

  When the cells are designed to form a particular type of blood cell, the uncommitted PHSCS are called committed PHSCS. Committed PHSC is defined as a cell, which is restricted to give rise to one group of blood cells.

Committed PHSCS are of two types:

1. Lymphoid stem cells (LSC) which give rise to lymphocytes and natural killer (NK) cells.

2. Colony-forming blastocytes, which give rise to myeloid cells. Myeloid cells are the blood cells other than lymphocytes. When grown in cultures, these cells form colonies hence the name colony-forming blastocytes

Different units of colony-forming cells are:

i. Colony-forming unit-erythrocytes (CFU-E): Cells of this unit develop into erythrocytes.

ii. Colony-forming unit-granulocytes/monocytes (CFUGM): These cells give rise to granulocytes (neutro phils, basophils and eosinophils) and monocytes.

iii. Colony-forming unit-megakaryocytes (CFU-M): Platelets are developed from these cells. 

Stem cells. L=Lymphocyte, R=Red blood cells, N=Neutrophil, B=Basophil, E=Eosinophil, M=Monocyte, P=Platelet.

CHANGES DURING ERYTHROPOIESIS

When the cells of CFU-E pass through different stages and finally become the matured RBCs. During these stages four important changes are noticed:                                                                    1. Reduction in size of the cell (from the diameter of 25 to 7.2 µ).

2. Disappearance of nucleoli and nucleus.

3. Appearance of hemoglobin.

4. Change in the staining properties of the cytoplasm.

STAGES OF ERYTHROPOIESIS

Various stages between CFU-E cells and matured RBCS are 

1. Proerythroblast.

2. Early normoblast.

3. Intermediate normoblast. 

4. Late normoblast.

5. Reticulocyte.

6. Matured erythrocyte.

1. Proerythroblast (Megaloblast)

 Proerythroblast or megaloblast is the first cell derived from CFU-E. It is very large in size with a diameter of about 20 µ. Its nucleus is large and occupies the cell almost completely. The nucleus has two or more nucleoli and a reticular network. Proerythroblast does not contain hemoglobin. The cytoplasm is basophilic in nature. Proerythroblast multiplies several times and finally forms the cell of next stage called early normoblast. Synthesis of hemoglobin starts in this stage. However, appearance of hemoglobin occurs only in intermediate normoblast.

2. Early Normoblast

The early normoblast is little smaller than proerythroblast with a diameter of about 15 µ. In the nucleus, the nucleoli disappear. Condensation of chromatin network occurs. The condensed network becomes dense. The cytoplasm is basophilic in nature. So, this cell is also called baso philic erythroblast. This cell develops into next stage called intermediate normoblast.

    

3. Intermediate Normoblast

Cell is smaller than the early normoblast with a diameter of 10 to 12 μ. The nucleus is still present. But the chro matin network shows further condensation. The hemo globin starts appearing.

Cytoplasm is already basophilic. Now, because of the presence of hemoglobin, it stains with both acidic as well as basic stains. So, this cell is called polychromophilic or polychromatic erythroblast. This cell develops into next stage called late normoblast.

4. Late Normoblast

Diameter of the cell decreases further to about 8 to 10 p. Nucleus becomes very small with very much condensed chromatin network and it is known as ink-spot nucleus.

Quantity of hemoglobin increases and the cytoplasm becomes almost acidophilic. So, the cell is now called orthochromatic erythroblast. In the final stage of late normoblast just before it passes to next stage, the nucleus disintegrates and disappears. The process by which nucleus disappears is called pyknosis. The final remnant is extruded from the cell Late normoblast develops into the next stage called reticulocyte

5. Reticulocyte

Reticulocyte is otherwise known as immature RBC. It is slightly larger than matured RBC. The cytoplasm con tains the reticular network or reticulum, which is formed by remnants of disintegrated organelles. Due to the retic ular network, the cell is called reticulocyte. The reticulum of reticulocyte stains with supravital stain.

In newborn babies, the reticulocyte count is 2 to 6% of RBCs, i.e. 2 to 6 reticulocytes are present for every 100 RBCs. The number of reticulocytes decreases during the first week after birth. Later, the reticulocyte count remains constant at or below 1% of RBCs. The number increases whenever production and release of RBCs in crease.                             Reticulocyte is basophilic due to the presence of remnants of disintegrated Golgi apparatus, mitochondria and other organelles of cytoplasm. During this stage,the cells enter the blood capillaries through capillary membrane from site of production by diapedesis.

Change during erythropoiesis

6. Matured Erythrocyte

 Reticular network disappears and the cell becomes the matured RBC and attains the biconcave shape. The cell decreases in size to 7.2 µ diameter. The matured RBC is with hemoglobin but without nucleus.

   It requires 7 days for the development and maturation of RBC from proerythroblast. It requires 5 days up to the stage of reticulocyte. Reticulocyte takes 2 more days to become the matured RBC.

FACTORS NECESSARY FOR ERYTHROPOIESIS

Development and maturation of erythrocytes require variety of factors, which are classified into three categories:

A. Stimulating factors.                                            B. Maturation factors.

C. Factors necessary for hemoglobin formation.