Erythropoiesis Lecture Notes PDF

ERYTHROPOIESIS Erythropoiesis A process by which early erythroid precursor cells differentiate to become the mature RBCs Primary regulator: ERYTHROPOIETIN - stimulates red cell precursors at all levels of maturation to hasten the maturation process - responsible for stimu...

ERYTHROPOIESIS Erythropoiesis A process by which early erythroid precursor cells differentiate to become the mature RBCs Primary regulator: ERYTHROPOIETIN - stimulates red cell precursors at all levels of maturation to hasten the maturation process - responsible for stimulating the premature release of reticulocytes into the bloodstream.  ERYTHROPOIESIS ◻ In adults, if 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. 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 Maturation 1. Pronormoblast 2. Basophilic Normoblast 3. Polychromatophilic Normoblast 4. Orthochromatic Normoblast 5. Reticulocyte 6. Erythrocyte Pronormoblast Earliest recognizable and largest cell of the erythrocyte series Morphology: ◻ Size: 12 – 20 um ◻ Nucleus: large round, oval, dark violet; fine chromatin; 1 – 2 nucleoli ◻ Cytoplasm: deep blue spotty, basophilic w/a perinuclear halo ◻ N/C Ratio: 8:1 ◻ BM (%): 1 ◻ No haemoglobin. ◻ Multiplies several times to form early normoblasts.  Basophilic Normoblast Hemoglobin synthesis begins at this stage Smaller than proerythroblasts Cell is also called EARLY NORMOBLAST. Morphology: ◻ Size: 10 – 15 um ◻ Nucleus: large round to oval; condensed, coarse chromatin; 0 – 1 nucleoli ◻ Cytoplasm: deeply basophilic; clusters of free ribosomes ◻ N/C Ratio: 6:1 ◻ BM (%): 1-4 ◻ These cells develops into next stage called intermediate normoblast.  Polychromatic Normoblast Increased production of hemoglobin pigmentation and decreasing amounts of RNA Last stage in which the cell is capable of mitoses Morphology: ◻ Size: 10 - 15 um ◻ Cytoplasm: abundant blue-gray (RNA) to pink-gray (hemoglobin) ◻ N/C Ratio: 4:1 ◻ BM (%): 10-20 ◻ Nucleus: round nucleus, deep staining, may be centrally or eccentrically located; coarse & clumped chromatin ◻ Nucleoli: 0 ◻ Cells are also called INTERMEDIATE NORMOBLAST Orthochromatic Normoblast The last nucleated stage Cannot synthesize DNA and cannot undergo cellular division The NRBC sometimes seen in the peripheral circulation Morphology: ◻ Size: 8 - 10 um ◻ Nucleus: small pyknotic nucleus; dense chromatin; 0 nucleoli ◻ Cytoplasm: abundant red-orange cytoplasm uniform in color ◻ Cells are also called LATE NORMOBLAST ◻ N/C Ratio: 1:2 ◻ BM (%): 5-10 Reticulocyte Slightly larger than the mature RBC with residual amount of RNA Reticulocyte count: an index of bone marrow activity or effective erythropoiesis Morphology: ◻ Size: 8 - 10 um ◻ Nucleus: anucleate cell containing small amount of basophilic reticulum (RNA) ◻ Nucleoli: 0 ◻ Cytoplasm: large amount of blue-pink staining hemoglobin cytoplasm Reticulocyte ◻ Immature RBC. ◻ Slightly larger than mature RBC. ◻ Reticulum. Remnants of disintegrated organelles. ◻ Named because of reticular network. ◻ In newborns, reticulocyte count is 2% to 6% of RBCs. ◻ Number decreases in first week of birth. ◻ In mature life, its below 1%. ◻ Count increases when production and release of RBCs increases. ◻ Basophilic because of remnants of golgi apparatus., mitochondria and other organelles ◻ Enter the blood through capillary membrane.  MATURED ERYTHROCYTES A biconcave 6 – 8 um disc Life span: 120 days Main function: to transport hemoglobin, a protein that delivers oxygen from the lungs to tissues and cells Contains 90% hemoglobin and 10% H2O Normal concentration of RBCs varies with age, sex & geographic distribution Morphology: ◻ Size: 7 - 8 um ◻ Nucleus: anucleated cell ◻ Nucleoli: 0 ◻ Cytoplasm: pink staining ◻ N/C Ratio: 0 MATURED ERYTHROCYTES ◻ Reticular network disappears. ◻ Cell becomes mature RBC. ◻ 7.2 micrometer. Biconcave shape. ◻ Haemoglobin but no nucleus. ◻ 7 days to convert to mature erythrocyte from proerythroblasts. ◻ 5 days to convert to reticulocytes from proerythroblasts. ◻ 2 days to convert to mature erythrocytes.  So in the Maturation of Erythrocyte ◻ Size of cell (decrease) ◻ Size of nucleus (decrease) ◻ Basophilia (decrease) ◻ Organelles (disappeared) ◻ Nucleus (extrusion) ◻ Polysome (disappeared) ◻ Ribosome ( disappeared in Reticulocyte to Erythrocyte) FACTORS NECESSARY FOR ERYTHROPOIESIS: ◻ Factors are generally classified into three categories: ◻ General factors. Erythropoietin Thyroxine. Hemopoietic growth factors. Vitamins. ◻ Maturation factors Vitamin B12. Intrinsic factor of castle. Folic acid ◻ Factors necessary for haemoglobin formation.