Module 4 Stem cell theory Membrane is important in erythrocytes for physiological reasons and aging maturation Growth factors give specificity and are VERY important Erythropoietin produced in kidneys because oxygen sensing mechanism is located there CD Cluster Designation proteins appear disappear as function of differentiation and maturation different proteins act as receptors making antobodies CD34 33 it is self explanatory First recognizable cell is the blast cell in each lineage Know diagram know pathways and all others RBC life span 120 days Erythropoiesis RBC count is a range and may change Look like sine graph normal RBC count falls within that range If the RBC count starts declining below normal range anemia creates hypoxia is the physiological stimulus so erythropoietic machine should get activated and the RBC count goes ABOVE because overcompensates then plateaus back to normal This is true for all blood cells If don t recover driven by bone marrow then hopefully spleen and liver will make up that differences Normoblastic erythrocyte maturation Reticulocyte contains remains of mRNA how we identify it Polychromasia related to reticulocytes and production in bone marrow Erythroblastic nest is when form in a cluster See granules non erythroid Percentage of cells in bone marrow 4 1 M E Bone marrow slide end stage of mitosis NRBC is only seen in newborns nucleated reb blood cell Effective Erythropoiesis VERY IMPORTANT SLIDE Time axis is left to right Start with a committed cell CFU E have cells before that have 4 stages before the first depicted cell in the picture DFU E gives rise to CFU E CFU GEMM gives rise to DFU E Pluripotential stem cell gives rise to CFUGEMM cont Hematopoietic potential to produce erythrocytes as they need to be made Proliferation Mature RBC Hemoglobin gives up its oxygen and carbon dioxide is made and will bind to hemoglobin It takes it back to the lungs and the cycle continues Biconcave disc is full of hemoglobin Important that hemoglobin is manufactured properly and that the contents are maintained this is where membrane importance comes in Membrane flexibility RBC are single file and have to be able to twist and turn Membrane is defective deformed if can t twist and turn through capillary and is destroyed Membranes are made of phospholipids remember phospholipid bilayer Proteins and lipids have important functions in RBC life cont Membrane controls rate of how the cells exists in its environment Fluid is plasma and lots of stuff float through this inc electrilytes Na Fe and K irons Na is extracellular ion Na concentration is greater outside than in inside so Na tries to get inside concentration gradient is name K is inside ion and is trying to get out This is forced equilibrium Na must have higher conc outside and K higher inside This is controlled by the membrane specifically Na K ATPase This requires energy The red cell gets energy from the two pathways on the slide EMB and HMP Mature RBC Energy Pathways EMB 90 is anaerobic Absence of oxygen HMP 10 aerobic Just memorize illustration side note Calcium magnesium have same relationship with pump EMB ATP HMP NADPH Oxidants are bad toxic Need antioxidants to keep GSH reduced glutathione Glutathione is necessary because protects hemoglobin Antioxidants work to neutralize GSH glutathione cont When O binds to hemoglobin the iron is actually doing the reaction Every hemoglobin must have iron bound to it Iron must be in Fe 2 state RBC Destruction Spherocytes are ages blood cells that have lost membrane fluidity are dense are more rigid have lost membrane flexibility Removal of spherocytes happens by rupturing extravasular hemaolysis Most of this is recycled back into body Post splenectomy blood findings All these aged cells are circulating in blood Is common to see all these bodies you normally do not see Pappenheimen too much iron Howell jolly nucleic acid remains RBC Indices Anemia is not a diagnosis just when peripheral blood count is below normal Most important