Hematopoesis
- creation of RBC
- Start in yolk sac; occurs in liver, and spleen for first couple of week of life; bone marrow produces for rest of life
extramedullary hematopoesis
Periods of extreme stress can cause blood cells being made in liver and spleen again
Hemaopoesis steps
hematopoetic stem cell–myeloid line–myeloid stem cell (EPO)–progenitor cell–proerythroblast–basophilic erythroblast–polychromatophilic erythroblast–orthochromatophilic erythroblast (nuceleus ejected)–reticulocyte – erythrocyte
Which cell can self-renew in hematopoesis?
-only hematopoetic stem cells
Look of cells with maturation
As cells mature they get smaller, nucelus gets darker, and cytoplasm goes from purple to pink (due to creating hemoglobin)
How to differentiate reticulocyte
Need supravital stain to stain RNA in reticulocyte
What controls hematopoesis?
EPO
- binds to erythropoietic progenitor cell
What causes stem cells to replicate?
-times of stress
What is released due to anemia?
why?
- Kidney will make because it senses hypoxia with hypoxia inducible factor
- EPO will go to bone marrow and bind to EPO receptor on progenitor cell
What happens with binding of EPO to progenitor cell?
-Binding of EPO to EPOR will bring ends of EPOR together (tyrosine kinase), and Jak2 autophosphorylates, increases transcription and cell differentiation
What happens to EPO with CKD?
- will have low erythropoietin because kidneys under stress
- so unable to replace RBC, leading to anemia
Erythrocytosis/ polycythemia
elevated hemoglobin and hematocrit
Primary erythrocytosis
-low EPO
Secondary erythrocytosis
-high EPO
High hemoglobin and hematocrit; low erythropoietin
RBC’s differentiating without EPO
V617F Jak2-mutation
- Gain of function mutation: constituively activates Jak 2– does not need binding of EPO for Jak2 to be activated and create RBC
- Polcythemia vera
Eero Mantyranta
- olympic gold medal winner
- Contained familial form of erythropoietin receptor mutation that allowed for increase in RBC; Had high hemoglobin and hematocrit; increase in oxygen carrying capacity
Polycthemia vera complications
When you have increased RBC, blood becomes thicker, clogs vessels and can cause low oxygen to tissue
Treatment for polcythemia vera
- will go through therapeutic phlebotomy (periodic blood donation)
- Could also use JAK2 inhibitor
High Hemoglobin, hematocrit, and EPO
- caused by tumor ( Glio-blastoma: brain tumor; most common type of tumor to secrete EPO, because very angiogenic)
- Similar symptoms as with low EPO, except for speech disturbances
- Will also treat with therapeutic phlebotomy, low dose aspirin, hydroxyurea, Jak 2 inhibitors
High hemoglobin and hematocrit, EPO normal
- caused by dehydration
- Pseudo polycythemia: Hemoglobin is a concentration, so if blood volume is low will look like concentration of hemoglobin is elevated
