hematopoiesis Flashcards
Hematopoiesis defintion/functions
- Define = formation of blood cells
- Functions
- provides the cellular elements (RBC’s and leukocytes) of the peripheral blood; takes place in the bone marrow
- delivery of oxygen to the tissues + providing host cell defense
Cell lifespans of differeing cells
- Granulocytes = 6-8 hours
- neutrophils, eosinophils, basophils etc
- most precursor cells (greater abundance than even red blood cell precursors)
- platelets = 7 to 10 days
- RBC = 120 days
- macrophages = months to years
- Lymphocytes = years
- especially memory T cells
Hematopoietic stem cells
- .1-.01% of bone marrow cells
- Give rise to progenitor cells of al llineages
- highest proliferative potential of any hematopoietic cell type
- capable of self-renewal and differentiation
- multipotential
- needs STROMAL CELLS AND CYTOKINES
Bone marrow stromal Cells
- Important role in maintenance + differentiation of hematopoietic cells
- examples = adipocytes, fibroblastoic cells and reticuloendothelials
- provide a microenviornment for differentiation
- stem cells/primative precurors bind FIRMLY to stromal cells (the younger the stronger the binding)
- Maturing precursor cells nonadherent (the older the cells, binding is less important)
- Differential expression of cell adhesion molecules regulates the binding activity
Role of cytokines
- Induce lineage-specific differentiation
- tell the cell what it needs to differentiate into
-
DOWNREGULATION of stem cell growth/differentiation by TGF-Beta by DECREASE cell surface receptors for growth/differentiation cytokines
- transforming growth factor beta = INHIBITS PRODUCTION OF CELLS (downregulates)
G-CSF
- G-CSF (granulocyte colony stimulating factor) released by macrophages at inflammatory sites
- circulates to bone marrow
- Production/release of NEUTROPHILS
EPO
- EPO produced/released by Peritubular interstitial cells (kidney) in response to hypoxia
- EPO circulates to bone marrow
- Production and release of RBC’s
- Increase oxygen pressure inhibits production of EPO
describe the clinical utility of cytokines
-
G-CSF
- stimulates granulopoiesis following chemotherapy-induced marrow suppression –> decrease change of infection + more frequent chemo
- BMT - mobilizes stem cells to blood. harvesting less invasive than bone marrow and decrease change of contaminating tumor cells
- GM-CSF
- Increase myeloid cell recovery in bone marrow transplantation patients
- more toxic than G-CSF –> thombosis and capillary leak syndrome
-
EPO
- anemia as a result of renal insufficiency –> icnreases RBC mass
Types of bone marrow
- Yellow marrow = normally INACTIVE and mainly adipose tissue
- Red Marrow = active in hematopoiesis
- first few years of life = all marrow is red
- by 18, red marrow is found in ribs sternum and pelvis
extramedullary hematopoiesis
- takes place in spleen and liver when bone marrow dysfunctional or unable to meet the demands on it
Maturational characteristics of erythropoiesis****
- As a cell matures
- Cell size DECREASE
- Nuclear: cytoplasmic ratio DECREASES (higher N:C ratio –> Lower N:C ratio)
- Nucleoli DECREASE in number and eventually disappear
- Cytoplasmic straining –> Darker blue to light blue (basophilic cytoplasm –> lighter cytoplasm)
Define erythropoiesis
- Definition = foration or production of RBC
- Starts: primitive RBC in the embryonic yolk sac
- continues in extramedullary organs (liver, spleen)
- Predominates in the red marrow during late fetal development
Maturation sequence: Stem cell –> rubriblast –> prorubricyte –> rubricyte –> metarubricyte –> reticulocyte –> mature erythrocyte
Granulopoiesis
* define: production of cell in the granulocytic lineage, including neutrophils, eosinophils and basophils
Sequence: stem cell –> myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> BAND –> granulocyte
- BAND CELL = almost, but not quite granulocyte…
- In circualtionm neutrophils evenly distributed between circulating and marginating pools (dynamic equilibrium maintained betwen two pools
Shift to a left
- The further to the right you go… the more mature you get
- Shift to the left means that you have MORE IMMATURE cells (band cells)
- seeing less mature neutrophils in the blood; signifiying the bone marrow can’t keep up with an infection or something
- Increase % of band forms in the blood termed “Shift to the left”
Monocytes - macrophages
- Macrophages develoop from monocytes and are distributed throughout the body with name being dependent upon location of the cells
- kupffer cells in liver, osteoclasts in bone etc
- Monocytes circulate for approximately 8 hours, then enter the tissues to differentiate into macrophages
Development stages: stem cell –> monoblast –> promonocyte –> monocyte –> macrophage