Lecture 1 Hematopoiesis, Abdulkarim Aldosari

Objectives Define hematopoiesis Describe the origin of hematopoieisis Define erythropoiesis List proper cell maturation of the erythrocytic series Identify three areas of RBC metabolism crucial for normal erythrocyte survival and function Describe RBC membrane biochemical structure and the consequences of structural membrane defects Describe Hemoglobin structure, function and synthesis RBC metabolic pathways

Hematopoiesis Blood cell formation – production and development Occurs bone marrow, liver, spleen, lymph nodes, thymus Bone marrow – sole site of effective hematopoiesis in normal adults 6 billion cells/kg of body weight per day 2.5 billion red cells 2.5 billion platelets 1.0 billion white cells Rate adjusted to need, vary from nearly zero to many times the normal Constant turnover of cells

Origin of Hematopoiesis Yolk sac > fetal liver/spleen > BM Primitive erythroblast > migrate to liver (6wks) – includes other myeloid and lymphoid cells. At birth the bone cavities are the only site of hematopoietic activity - Starts at 7 months Fig 1-16, pg. 10

Origin of Hematopoiesis

Origin of Hematopoiesis Shaft of long bones – until 4 yrs. Sternum, ribs, pelvis, vertebrae, skull – at 18-20 yrs. Other bones have mostly yellow marrow (fat) At 40 yrs – equal amount of yellow and red marrow

Origin of Hematopoiesis Takes place in the entire medullary space during infancy and early childhood Later – occurs in the extravascular part of red marrow Squeeze through the endothelial lining cells that separates the extravascular marrow from the intravascular compartment- venous sinus Migrating cells enter the peripheral blood

Hematopoiesis Steady state of hematopoiesis i.e. production = removal During increased demand for blood cells strenuous exercise, high altitudes, smokers To compensate - Spleen, liver and other tissues can start active hematopoiesis = Extramedullary hematopoiesis Two pools of cells participate in hematopoietic activity: Stem cell pool Bone marrow pool

Hematopoiesis Hematopoietic stem cell pool Pluripotential - multipotential stem cells (MSCs) morphologically identical Continuous self-renewal Unipotential - committed progenitor cells Restricted to single cell line No self-renewal Lymphoid or myeloid Fig 1-15, pg. 9

Figure 1-15

Hematopoiesis Bone marrow pool Cells released to peripheral blood proliferating and maturing cells - through the action of cytokines (growth factors) – CSF and IL progenitor cells divide and differentiate Stored cells for later release to peripheral blood Cells released to peripheral blood Storage – WBCS , platelets Functional – WBCs, platelets, RBCs Fig 1-17, pg. 10