ERYTHROPOIESIS

In adults, liver and spleen produce RBCs if bone marrow is destroyed or fibrosed. Bone marrow is equal to liver in size and weight. Involved in the production of cells. 75% leukocytes are produced and 25% erythrocytes. WBC-RBC ratio: 1:500 Difference in life span.

Erythropoiesis: Process of origin, development and maturation of red blood cells. Hemopoiesis or hematopoiesis: Process of origin, development and maturation of all blood cells.

PROCESS OF ERYTHROPOIESIS: STEM CELLS: Blood cells are formed in the bone marrow from stem cells called pluripotential haematopoietic stem cells. Also called uncommitted pluripotential haematopoietic stem cells (PHSC). All the cells of circulation are derived from these cells. During reproduction, few PHSC remain like the cells of origin to maintain the supply. When cells are differentiated to form particular types of blood cells, uncommitted PHSC are converted to committed PHSC. These are the cells restricted to give rise to specific type of blood cells.

Two types of PHSCs: 1. lymphoid stem cells: Lymphocytic cells i.e. T-Lymphocytes & B-lymphocytes 2. Colony forming unit- Spleen Myeloid cells. When grown in culture these cells form colonies.

Units of colony forming cells: A committed stem cell that forms erythrocytes is called colony forming unit erythrocytes. CFU-E Colony forming units that form granulocytes and monocytes have designation CFU-GM. These cells give rise to neutrophils, eosinophils and basophils. Colony forming unit-megakaryocytes CFU-M. Platelets are developed from these cells.

Changes during erythropoiesis: CFU-E in the process of maturation pass through 4 stages: Reduction in size of cells: 25 to 7.2 micrometer. Disappearance of nuclei and nucleus. Appearance of haemoglobin. Changes in the staining properties of cytoplasm.

STAGES OF ERYTHROPOIESIS: 1. Proerythroblast. 2. Early normoblast. 3. Intermediate normoblast. 4. Late normoblast. 5. Reticulocyte. 6. Matured erythrocyte.

1.PROERYTHROBLAST: Megaloblast First cell derived from CFU-E Large with 20 micrometer diameter. Cytoplasm is basophilic in nature. Large nucleus occupying the cell completely. Nucleus has 2 or more nucleoli and reticular network. No haemoglobin. Multiplies several times to form early normoblasts.

2. EARLY NORMOBLAST: Synthesis of haemoglobin starts in this stage. Smaller than proerythroblasts. 15 micrometer diameter. Cytoplasm is basophillic in nature. Cell is also called basophilic erythroblast. Nucleoli disappear. Chromatin network becomes dense. These cells develops into next stage called intermediate normoblast.

3. INTERMEDIATE NORMOBLAST: Haemoglobin appears in this stage. Cells have diameter of 1-0-12 micrometer. Nucleus is still present. Chromatin network is further condensed. Cytoplasm is basophilic. Due to haemoglobin it stains both acidic and basic. Cells are also called polychromophilic or polychromatic erythroblast. Develop into late normoblast.

4. LATE NORMOBLAST: 8-10 micrometer

Reticulocyte: Cytoplasm filled with 34% Hb Neucleus & ER reabsorbed Cell passes into blood capillaries by Diapedesis

Mature Erythrocyte Remaining basophillic material disappears in 1 or 2 days and reticulocyte converts into mature erythrocyte.

Regulation of Erythropoiesis Tissue oxygenation is basic regulator of RBC production Low blood vol., low blood flow, low Hb, anemia, failure of O2 absorption in pulmonary disease, dec. Tissue oxygenantion Secretion of hormone “Erythropoietin (glycoprotein)” from 80 to 90% from kidneys and rest from liver and macrophages, It stimulates production of pro-erythroblast from hemopoietic stem cell which in turn inc. RBC production.

Life Span of RBCs RBCs have no nucleus, mitochondria and ER They have enzymes of glycolysis and hexose monophosphate shunt to use glucose for ATP production. So they are alive for 120 days. After which these enzymes are depleted