Hematopoiesis Flashcards
What bones are used in blood cell synthesis?
Skull, ribs, sternum, vertebrae, pelvis, proximal femurs
All cells are derived from a single […] stem cell.
Pluripotent hematopoietic
What are the two cells that directly arise from a hematopoietic stem cell (HSC)?
Common myeloid progenitor (CMP) and common lymphoid progenitor (CLP)
Define three lineages to produce multiple cell types
- Granulocyte monocyte progenitor
- Megakaryocyte progenitor
- Common lymphoid progenitor
What are the 3 phases of hematopoiesis in embryonic development?
- Starts in fetus during 1st trimester where we get the development of hematopoietic islands in the umbilical vesicle
- Continues after 2nd trimester in liver and then in spleen
- During the 7th month, the bone marrow becomes the primary site of hematopoiesis.
What does bone marrow consist of?
Blood vessels, hematopoietic cells, and sinusoids
Define sinusoids
Unique vascular unit with an endothelial lining, discontinuous basement membrane (open and porous), and an incomplete covering of adventitial cells
Define adventitial cells
They provide support for developing blood cells via producing reticular fibers and cytokine secretion
What is between the sinusoids and the actual bone marrow tissue that is functionally active?
Hematopoietic cords which contain HSCs
4 steps of cell migration across the bone marrow endothelium
- Maturing blood cell or megakaryocyte process pushes against an endothelial cell
- Will fuse and pierce luminal plasma membrane
- Each blood cell/process must squeeze through the aperture and enter sinusoidal lumen
- Endothelial cells repairs itself and aperture disappears
What type of bone contains bone marrow?
Spongy bone
Where is red bone marrow located
Within medullary cavity of young long bones and spaces of spongy bone
What is yellow bone marrow composed of, and where is it found?
Predominantly composed of adipose cells, and is found in medullary cavity of adult bones which are no longer hematopoietically active
How do you calculate normal cellularity of bone marrow?
Subtract individuals age from 100 and then ± 10%
What does cellularity of bone marrow represent?
Represents ratio of HSCs to adipocytes
Define hypocellular marrow.
What can cause this?
Small number of HSCs.
Caused by aplastic anemia and chemotherapy
Define hypercellular marrow.
What can cause this?
This is bone marrow affected by HSC tumors.
Caused by acute myelogenous leukemia
What is the difference between a bone marrow aspirate and a core biopsy?
Aspirate is when a needle is inserted through the skin and penetrates the bone.
Core biopsy is when the needle is advanced into the bone with a rotating motion and withdrawn, which collects a small, solid piece of bone marrow.
What are hematopoietic growth factors for?
They allow for control proliferation and maturation phases of hematopoiesis.
What are the 3 major groups of hematopoietic growth factors?
- Colony-stimulating factors (CSF)
- Erythropoietin (EPO) and thrombopoietin (TPO)
- Interleukins (cytokines)
Common myeloid progenitor (CMP) cells directly give rise to what two cell types?
- Megakaryocyte/erythrocyte progenitor (MEP)
2. Granulocyte/monocyte progenitor (GMP)
What regulates erythropoiesis?
Erythropoietin (EPO)
What growth factors influence the conversion of CMP → MEP?
EPO, IL-3, and IL-4
MEP → ?
Erythropoietin-sensitive erythrocyte-committed progenitors (ErP/CFU-E)
What is required for terminal differentiation to erythroid lineage?
GATA-1
ErP → ?
Characteristics?
Proerythroblast
Cytoplasm is basophilic. Large cell. Recognizable, but not easily identified.
Proerythroblast → ?
Characteristics?
Basophilic erythroblast
Small nucleus, cytoplasm contains strong basophilia
Basophilic erythroblast → ?
Characteristics?
Polychromatophilic erythroblast
Acidophilic and basophilic staining of cytoplasm. Additionally, nucleus is smaller than basophilic.
Polychromatophilic erythroblast → ?
Characteristics?
Orthochromatophilic erythroblast.
Increased acidophilia, and no longer capable of division
Orthochromatophilic erythroblast → ?
Characteristics?
Polychromatophilic erythrocyte.
These are better known as reticulocytes and contain no nucleus.
What growth factors stimulate thrombopoiesis?
GM-CSF and IL-3 which influence differentiation of megakaryocyte/erythrocyte progenitor (MEP)
In thrombopoiesis, HSC → ? → ? → ? → finally give rise to megakaryocyte
HSC → CMP → MEP → megakaryocyte progenitor (MKP) → megakaryocyte.
What type of cell will undergo numerous chromosomal duplications up to n=64, but will never undergo cytokinesis?
Megakaryocyte
Where is thrombopoietin (TPO) produced?
Liver and kidneys
Since megakaryocytes are too big to squeeze through the endothelial cells that make sinusoids, they instead do what?
They instead extend long, cytoplasmic processes (proplatelets) through the endothelial openings and wait for some type of collision to break off pieces of the processes, which are referred to as platelets.
Granulopoiesis stimulate the formation of…
Neutrophils, eosinophils, basophils, and monocytes.
In granulopoiesis, what growth factors stimulate a CMP → GMP?
GM-CSF and IL-3
What are the 4 steps of granulopoiesis?
Myeloblast (no cytoplasmic granules) → Promyeloblast (First azurophilic granules appear) → Myelocyte (Moderate # of azurophilic granules and first production of specific granules. nucleus develops indentation) → Metamyelocyte (abundant specific granules. Will give rise to banded cells)
Define a neutrophil shift
An increase in immature neutrophils entering the reserve pool.
In sudden and extremely severe infections, reserve granulocytes are drained faster than the increased production can replace them.
If band forms, metamyelocytes and myelocytes enter the circulation, we get a […]
If we get an increase of mature blood cells (not commonly scene), we get a […]
left shift.
Right shift.
Monocytes are produced from a […] which differentiates into a […]
Dependent on what growth factors
GMP
Monocyte progenitor cell (MoP/monoblast)
PU.1, Egr-1, IL-3, GM-CSF
Monocyte → macrophage transformation requires what growth factors?
GM-CSF and M-CSF
Lymphocytes and NK cells develop from the […]
common lymphoid progenitor cell (CLP)
What differentiates T-cells from B-cells
T-cells produced in BM and mature in thymus. Requires ikaros and GATA-3.
B-cells produced in BM and mature in BM. Require Ikaros and Pax5.
