1 Overview of Hematopoiesis Flashcards
When in the fetus (weeks or months) does hematopoiesis occur only in a yolk sac? liver and spleen? only bone marrow?
- <6 weeks
- 6 wks to 7 months
- 7 months onward
In infancy, what bones have hematopoiesis?
All bones… then fatty replacement and hematopoiesis only in central skeleton
The production of blood cells outside of the marrow space?
extramedullary hematopoiesis-most common in fetal spleen and liver
What supplies oxygenated blood to marrow?
nutrient arteries and periosteal capillary network
How does blood leave marrow?
thin endothelial lined sinusoids
What borders sinusoids in marrow?
adventitial reticular cells
What regulates passage of hematopoietic cells into systemic circulation?
adventitial reticular cells
What direction does the sinusoids drain?
periphery to center of the marrow–emptying into central vein
What produces structural scaffolding for bone marrow extravascular compartment??
stromal cells- fat cells, macrophages, reticular cells, fibroblasts
t-f, T cells and macrophages cannot produce regulatory factors or cytokines in bone marrow?
false
Are most pluripotent, self renewal hematopoietic stem cells very active?
No-quiescent
Is differentiation reversible?
No
What do HSC express on surface and are identified by?
CD34
Is there a higher frequency than stems for the committed progenitor cells?
Yes–myeloid and lymphoid
What cells (or stage) are recognizable by microscopic examination of the marrow?
Late precursors and mature blood cells
Are hematopoietic growth factors soluble or membrane bound?
Both—most are cytokines
What produces hematopoietic GFs?
stromal cells, endothelial cells, HEMATOPOIETIC STEM CELLS, fat cells, macrophages
Glycoprotein c-kit ligand is important for?
proliferation, migration and adhesion of stem cells
What type of ligand is FLT-3?
tyrosine kinase ligand
IL-3 does what to myeloid progenitors?
stimulates proliferation….GM-CSF does this also
What are the major pathways caused by dimerization of receptors in hematopoietic cells?
JAK/STAT
MAP
PI3
What is the earliest committed erythroid precursor?
BFU-e (burst forming unit-erythroid)
What stage comes after BFU-e stage?
CFU-e (colony forming unit-erythroid)
What is the main important growth factor for erythroid cells? what is it produced by?
erythropoietin (EPO)
produced by peritubular kidney cells in response to hypoxia
when is erthropoietin effective and what does it induce?
red cell production from BFU-e stage through maturation—about 25% of marrow cells are maturing red cells from the CFU-e onward stages
What are the stages of hemoglobin accumulation?
pronormoblast basophilic normoblast polychromatophilic normoblast orthochromic normoblast polychromatophilic red cell erythrocyte
How long do red cells live in circulation?
120 days
What is the major growth factor for granulocytes?
GM-CSF and IL-3
What does CFU-GM differentiate into?
CFU-G and CFU-M (GFs are G-CSF and M-CSF)
further maturation is caused by these same GFs until neutrophil and monocyte
Myeloid maturation steps?
myeloblast>promyelocyte>myelocyte>metamyelocyte>band>segmented neutrophil
What are dendritic cells, osteoclasts and macrophages derived from?
monocyte precursors
What is thrombopoiesis?
production of platelets (megakaryopoiesis too)
What are the progenitors for megakaryopoiesis?
BFU-MEG and CFU-MEG
GFs= IL-3, IL-6, IL-11, SCF
What GF has specificity for CFU-MEG and maturing megakaryocytic and promotes proliferation and differentiation? where is it synthesized?
Thrombopoietin (TPO), LIVER
What regulates production of thrombopoietin?
platelet mass and decreased platelet counts upregulate
Are megakaryocytic found in large numbers in the bone marrow?
no
What is cell growth, DNA replication and nuclear division without cytoplasmic division? example?
endomitosis-(megakaryocytes)
muliploid cells with nuclear content 8-32N
What are cytoplasmic fragments of megakaryocytic?
platelets–live for 7-10 days
