Hematopoiesis Flashcards
Stem cells characteristics
may proliferate extremely well
self-renewing
may differentiate into several (at least 2) different cell-Types
may reconstitute tissues after injury
What does Totipotent
Cells give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development).
Is a zygote totipotent
yes
What is pluripotent
Pluripotent cells give rise to all cells fo the embryo and subsequently adult tissues (embryonic stem cells)
Are embryonic stem cells totipotent, pluripotent, or multipotent
pluripotent
What is multipotent
Multipotent cells give rise to different cell types of a given lineage (adult stem cells).
Embryonic stem cells are derived from
Inner-Cell mass of blastocyst
Embryonic stem cells may be induced from ____ tissues
adult
Adult stem cells are harvested from
mature organs/tissues (bone marrow)
Adult stem cells are totipotent, pluripotent, or multipotent
multipotent
What limitations do adult stem cells have vs. embryonic stem cells
more restricted ability to produce different cell types and to self-renew
At 2-8 weeks of gestation islands of hematopoiesis (blood islands) are found in the ______
Yolk sac wall
at 208 weeks of gestation the islands of hematopoiesis (blood islands) in the yolk sac wall give rise to
nucleated erythrocytes
Do leukocytes form during 2-8 weeks of gestation
No
During 8-28 weeks of gestation hematopoiesis first occurs in the ___ and then the ____
liver and then the spleen
Hematopoiesis in the liver and spleen ceases around the time of
Birth
when does hematopoiesis begin to occur in the red bone marrow
6 months gestation to birth and beyond
At birth all the bone marrow is
Red marrow
Red bone marrow is the source of
all blood cells
Prior to puberty red bone marrow is located in
skull, ribs, sternum, vertebrae, clavicles, pelvis, long bones
After puberty red bone marrow is located in
Skull, ribs, sternum, verebrae, clavicles, and pelvis
In time, most of marrow is converted to _____ marrow, and red marrow is usually restricted to _____ and _____
yellow, sternum, iliac crests
What is extramedullary hematopoiesis
in certain disease states, blood cell formation may occur in liver and spleen
The stroma contains what kind of cells
fibroblasts, reticular cells, adipose cells, and endothelial cells
The stroma synthesizes and secretes
Hematopoietic growth factors
The parenchyma consists of
Various lineages of hematopoietic cells in different stages of differentation
What are sinusoids
endothelial-lined spaces that connect arterial and venous vessels
What is the function of sinusoids
provides access for mature blood cells to move into the circulation
What hematopoietic cords
Bands of parenchyma and stroma lying between the sinusoids
What is the total percent of granulocytopoiesis
60%
What is the percentage of erythrocytopoieis
30%
What is the percentagge of thrombocytopoiesis, monocytopoiesis, lymphocytopoiesis
10%
What is Myeloid/erythroid ratio
total volume of cells in granulocytopoiesis/ total volume of cells in erythrocytopoiesis
What is the normal myeloid/erythroid ratio
3:1
What is the ratio of myeloid/erythroid that is an example of chronic myelogenous leukemia
8:1
What is the ratio of myeloid/erythroid that shows a polycythemia
1:5
Granulocyte-macrophage CFU can become what
macrophages and neutrophils
Mature blood cells migrate from the _________through the sinusoidal endothelial walls into the sinusoids
Hematopoietic cords
___________ (site of platelet production) are too large to translocate and must remain in the stroma
Megakaryocytes
Hematopoietic stem cells are pluripotent and commiteed to what two stem cell lineages
myeloid or lymphoid stem cell lineages
Can hematopoietic stem cells self-renew
yes
Hematopoietic stem cells produce two kinds of ________ precursor cells, and what are they
multipotential, myeloid stem cell, lymphoid stem cell
What do myeloid stem cells give rise to
all blood cell lines except lymphocytes
What do lymphoid stem cells give rise to
lymphocytes
How are hematopoietic stem cells identified
Can’t be identified by morphology but can be recognized by cell surface markers
Luekocytes differentiate into what two sub classes
granulocytes and agranulocytes
What are the three types of granulocytes
Neutrophils, Basophils, and Eosinophils
What are the two types of agranulocytes
Monocytes and lymphocytes
Myeloid stem cells give rise to how many kinds of colony-forming units
5
What are the 5 colony forming units that myeloid stem cells give rise to
Erythroid CFU Megokaryocyte CFU Basophil CFU Eosinophil CFU Eosinophil CFU Granulocyte-Macrophage CFU
Erythroid CFU gives produces what kind of cells
Erythrocytes (red blood cells)
Megokaryocyte CFU produces what kind of cells
Platelets
Basophil CFU is acted on my ______ to produce myelobast
SFC (stem cell factor or c-kit ligand)
What acts on Granulocyte-Macrohage CFU to produce neutrotphils
G-CSF
What acts on Granulocyte-Macrophage CFU to produce Monoblasts
M-CSF
What acts on Erythroid CFU to produce proerythroblasts
Erythropoietin
What acts on Megokaryocyte CFU to produce megakaryocytoblast
Thrombopoietin
What type of cell (s) produce G-CSF
endothelial cells, fibroblasts, and macrophages
What are the three major groups of hematopoietic growth factors
colony-stimulating factors, Erythropoietin and thrombopoietin, Cytokines (primarily interleukins)
What is the function of GM-CSF
it leads to the myeloid stem cell becoming basophil CFU, Eosinophil CFU, or Granulocyte-macrophage CFU
What is the function of Interleukins
Act on hematopoietic stem cells to protduce Lymphoid stem cell
T-cells mature in the
Thymus
B-Cell mature in the
Bone marrow
describe the lineage of macrophage
Hematopoietic stem cells–> Myeloid Stem cell–>Granulocyte-macrophage CFU—> Monoblast—> promonocyte–> Monocyte—> Macrophage
In the macrophage lineage what is the cell type that is normally found in the blood
Monocyte
Describe the cell lineage of a Neutrophil
Hematopoietic stem cell–> Myeloid Stem Cell–> Granulocyte-Macrophage CFU–> Myeloblast —> Promyelocyte—> Myelocyte —> Metamyelocyte—-> Band cell—-> Neutrophil
What are the cells in the Neutrophil cell lineage that can be found in the circulation
Band cells (not common unless rapid turnover of neutrophils) Neurtrophils
What are macrophages in the bone named
Osteoclasts
What are macrohages in the skin named
Langerhans cells
What are macrophages in brain named
Microglia cells
Where are macrophages found in the spleen
in the red pulp
What are macrophages in the liver called
Kupffer cell
What are macrophages in the lungs called
alveolar macrophage or dust cell
What percentage of cells in the liver are kupffer cells
56%
Monocytes circulate for how long before migrating into tissues
14 hours
What percentage of cells in the lungs are dust cells
15%
What are the two cell niches
Vascular niche and Endosteal niche
Mast cells are derived from
Basophils
Band cells turn into
Eosinophil, Neutrophil, and Basophils
What is the lineage for eosinophils and basophils
hematopoetic stem cell–> myeloid stem cell –> Eosinophil CFU or Basophil CFU—> Myelobast—-> Promyelocyte—-> myelocyte—-> metamyelocyte–> Band cell–> eosinophil or basophil
What is cell lineage for platelets
Megakaryocyte CFU—> megakaryoblast–> megakaryocyte—-> platelets
What is the cell lineage for a erythrocyte
erythroid CFU–> proerythroblast–> basophilic erythroblast–> polychromatophilic erythroblast—> orthochromatic erythroblast—> Reticulocyte—-> Erythrocyte
What cells in the erythrocyte lineage can be found in circulation
Reticulocytes and erythrocytes
When are reticulocytes found in blood
when someone is rapidly forming red blood cells. often when dealing with acute anemia. they are called reticulocytes because they have remnants of their rough ER
Hematopoietic growth factors and cytokines are produced by
endothelial cells in the marrow, fibroblasts, and stromal cells
Hematopoietic growth factors and cytokines are all glycoproteins
yes
GM-CSF is produced by
endothelial cells, T cells, firboblasts, and monocytes
GM-CSF stimulates
Granulocytopoiesis and moncytopoiesis
what is used to ameliorates neuropenia associated with chemotherapy or radiation therapy
GM-CSF and G-CSF
What are the synthetic forms of GM-CSF
Sargramostim or melgramostim
G-CSF is produced by
endothelial cells, fibroblasts, and macrophages
What is the function of G-CSF
Directs CFU-GM to proliferate and differentiate into myeloblasts
What is the function of M-CSF
commits CFU-GM to monocytic pathway
What is the function of erythropoietin
Directs CFU-E to proliferate and differentiate into proeryhtroblasts
Where is erythropoietin produced
Produced by the interstitial cells in the renal cortex in response to decrease in oxygen saturation
What is secondary polycythemia
abnormal increase in total RBC mass resulting from hypoxia and stimulating release of erythropoietin
Possible causes include Tetralogy of Fallot and Cigarette smoke
What is the function of thrombopoietin
directs formation of megakaryoblasts
Where is thrombopoietin formed
in the proximal convoluted tubules of the kidney
and in parenchymal cells and sinusoidal endothelial cells of liver
What is the function of cytokines (primarily interleukins)
mediate positive and negative affects on cellular quiescence, apoptosis, proliferation, and differentiation
engage specific receptors and activate a variety of signaling pathways
Cytokins (primarily interleukins) engage ______ and activate what
specific receptors and activate a variety of signaling pathways
What are some examples of cytokines (primarily interleukins)
Interleukin-3
GM-CSF
Fit-3 ligand
Kit ligand
What are the functions of chemokines
regulate blood cell trafficking and homing to sites of need
may serve as positive and negative growth regulators
Where do chemokines bind
to guanine protein-coupled transmembrane receptors
What is an example of a chemokine
Sdf-1
What are some ECM components that regulate hematopoesis
Heparin sulphates, collagens, laminin, fibronectin
Chemokins may serve as what
positive and negative hematopoietic growth factors