Hematopoiesis Flashcards
Where/how does hematopoiesis begin in the fetus?
hemangioblasts –> hematopoietic islands in umbilical vesicle/yolk sac (1st trimester) –> liver and spleen (2nd trimester) –> bone marrow (7th month)
What is the overall makeup of bone marrow?
blood vessels
hematopoietic cells
sinusoids
What is a sinusoid?
vascular unit of BM
endothelial lining, discontinuous basement membrane, and incomplete covering of adventitial cells
What are adventitial cells?
- incompletely surround sinusoids of bone marrow
- provide support for developing blood cells
- produce reticular fibers and secrete cytokines
where do hematopoietic cells lie in bone marrow?
in cords in btwn sinusoids
How do maturing blood cells enter a sinusoid to enter blood?
cells push against endothelial cell –> fuse and pierce luminal PM –> forms opening and squeezes through to sinusoidal lumen –> endothelial cell repairs itself
How do megakaryocytes enter the sinusoidal lumen?
too big for entire cell to go
proplatelets extend through –> blood flow breaks it into platelets in blood
Where is red bone marrow found?
in medullary cavity of young long bones
in flat bones in adults
What are the predominant cell types/products in red bone marrow?
hematopoietic cords are predominately making blood cells and megakaryocytes
(macrophages, mast cells, and some adipose cells are also present)
What is the predominant cell type of yellow bone marrow?
adipose cells (not very hematopoietically active)
In active bone marrow in an adult, what is the ratio of adipose to hematopoietic tissue?
50:50
How do you calculate the normal cellularity of a person’s bone marrow?
100 - person’s age + or - 10%
30 year old = 60-80% active cells
What is hypocellular marrow?
fewer blood-forming cells are found than expected
aplastic anemia, chemotherapy
What is hypercellular marrow?
more blood-forming cells than expected
usually because of tumors
What is the difference between a bone marrow aspirate and and bone marrow core biopsy?
In both, needle is inserted into bone marrow
in core biopsy: try to keep marrow architecture in tact; don’t do a smear; do rotating motion
in aspirate: spread as a smear, don’t have to rotate needle
What are the 3 major groups of hematopoietic growth factors?
colony-stimulating factors (CSF)
erythropoietin (EPO) and thrombopoietin (TPO)
interleukins (cytokines)
What do HSCs give rise to immediately?
common myeloid progenitor (CMP) cells
OR: Common lymphoid progenitor (CLP) cells
What do common myeloid progenitor cells give rise to?
MEP: megakaryocyte/erithrocyte progenitors
OR: GMP: granulocyte/monocyte progeniotrs
what is erythropoiesis regulated by?
erythropoietin (EPO) = secreted in response to low O2; acts on surface receptors of the ErP
GATA-1 is required for terminal differentiation
How would an MEP differentiate to the erythrocyte lineage?
EPO, IL-3, and IL-4 act on MEP –> to erythropoietin-sensitive erythrocyte-committed progenitor (ErP/CFU-E)
(GATA-1 required)
What is the overall sequence of precursors to form an erythrocyte?
HSC –> Common myeloid precursor –> MEP –> ErP –> Proerythroblast –> basophilic erythroblast –> polychromatophilic erythroblast –> orthochromatophilic erythroblast (normoblast) –> polychromatophilic erythrocyte (reticulocyte) –> erythrocyte
What characterizes a proerythroblast?
large cell
cytoplasm is basophilic
recognizable, but not easily identified
What characterizes a basophilic erythroblast?
small nucleus
cytoplasm w/ strong basophilia
accumulation of Hb will gradually change staining
What characterizes a polychromatophilic erythroblast?
acidic and basophilic staining
nucleus is smaller than basophilic erythroblast
What characterizes an orthochromatophilic erythroblast/normoblast?
more acidophilic staining of cytoplasm and dense purple nucleus
no longer capable of division
will extrude nucleus and pass into sinusoids
What characterizes a polychromatophilic erythrocyte/reticulocyte?
acidophilic staining
special stains highlight polyribosomes
1-2% of RBC count
What is thrombopoiesis?
formation of thrombocytes/platelets