Hematopoiesis Flashcards
Where does hematopoiesis take place?
Bone Marrow
What is the cell lifespan of: Lymphycytes, RBCs, Platelets, Granulocytes?
Lymphocytes: years
RBCs: 120 days
Platelets: 7-10 days
Granulocytes: 6-8 hours
What are some important characteristics of Hematopoietic Stem Cells?
- Make up a very small amount of bone marrow cells (0.1 - 0.01%)
- Give rise to progenitor cells of all lineages
- Cannot be identified morphologically
What is the role of Bone Marrow Stromal Cells?
Maintenance and Differentiation of hematopoietic cells via CONTACT throughout the differentiation process
(Bind less and less as the cells mature)
What is the function of Cytokines in Hematopoiesis? (Progenitor Cell Cytokines vs. End-Stage Cytokines)
Cytokines drive specific cell differentiation pathways
Progenitor Cell Cytokines: (e.g. Stem Cell factor) act on immature cells
End-Stage Cytokines: act on more differentiated cell types to induce lineage specific differentiation
What is G-CSF and what is it’s function?
What type of cell releases G-CSF and where?
G-CSF (Granulocyte Colony Stimulating Facor) is a cytokine that calls the bone marrow to produce granulocytes (e.g. Neutrophils, eosinophils, and basophils), which then traffic to the site of inflammation and phacoytize bacteria
Released by macrophages at inflammatory sites
What is EPO, where is it produced, why is it produced, and what does it do?
What inhibits EPO?
EPO (Erythropoietin) is a cytokine produced by the peritublar interstitial cells (Kidney) in response to hypoxia.
EPO tells the bone marrow to increase production and release of RBCs
EPO is inhibited by Increased Oxygen Pressure
What is TGF-B and what does it do?
TGF-B is a cytokine that DOWNREGULATES stem cell growth/differention by decreaseing cell surface receptors for growth/differentiation of cytokines
What is G-CSF used for clinically? (2 things)
- Stimulates the bone marrow to release stem cells into the blood, which can then be harvested using a Flow Cytometer (Cell Sorter)
***Much less invasive, lower chance of infection than sticking a needle into their bone marrow***
- Stimulates granulopoiesis (especially Neutrophils) following c__hemotehrapy/bone marrow cell production
What is the clinical utility of GM-CSF? (Granulocyte Monocyte Colony Stimulating Factor)
***Stimulates both granulocytes and monocytes (eventually become macrophages)***
- Increases myeloid cell recovery in bone marrow transplant patients
- MORE TOXIC than G-CSF (e.g. Thrombosis and Capillary Leak Syndrome) so usually not given (G-CSF given instead)
What is the clinical utility of EPO?
- Used to treat anemia as a result of renal insufficiency
***Increases RBC mass***
What are the two forms of Bone Marrow and Where are they found?
Yellow Marrow: normally inactive and mainly found in adipose tissue
Red Marrow: active in hematopoiesis
- First few years of live –> all marrow is Red
- By age 18, red marrow is found in the ribs, sternum, and pelvis
Where does extramedullary hematopoiesis take place?
Spleen and liver when bone marrow is dysfunctional/unable to meet demands
What are the four things to be aware of concerning Erythropoiesis?
- Cell Size decreases
- Nuclear:Cytoplasm ratio decreases
- Nucleoli decrease in number, eventually disappear
- Cytoplasm goes from darker blue to lighter blue due to decreased RNA
What happens when the RBC matures from a Metarubricyte to a Reticulocyte?
It loses its nucleus
When does Erythropoiesis start, continue, and predominate?
Starts: Primitive RBCs in the embryonic yolk sac
Continues: extramedullary organs (i.e. Liver and Spleen)
Predominates: in the red marrow during late fetal development
What is a Reticulocyte?
The stage of RBC maturation just before an Erythrocyte
What will lead to an increased Reticulocyte count?
Will increase as erythropoiesis is highly active (Bone marrow is trying to push them out as fast as possible)
What cells are produced during Granulopoiesis?
Neutrophils, Eosinophils, and Basophils
What is a Band Cell and when will you see it? Percentages (normal vs. infection)
A slightly immature granulocyte (e.g. Neutrophil - will have a horseshoe nucleus compared to regular neutrophil) that will appear in the blood when the bone marrow is trying to push out cells as fast as possible
Normal: 3-5%
Bacterial Infection: 20-25%
What is a Left Shift or Shift to the Left?
Used to describe increased percentage of Band Cells in the blood
Where are neutrophils normally located (Two Pools) in the blood stream?
50% are traveling in the blood stream (in Motion)
50% are loosely attached to the vascular endothelial cells (Stationary)
***This is a DYNAMIC process***
What are Monocytes and Where are they produced?
Monocytes are baby Macrophages that are produced in the bone marrow
What are Macrophages called in: Loose Connective Tissue, Liver, Osteoclasts, and Nervous System?
Loose Connective Tissue –> Histiocytes
Liver –> Kupffer Cells
Bone –> Osteoclasts
Nervous System –> Microglial Cells
How long do Monocytes last? Macrophages?
Monocytes circulate for ~8 hours then enter tissues and differentiate into macrophages
Macrophages live months to years
What kind of cells does Lymphopoiesis produce?
T lymphocytes, B lymphocytes, and Natural Killer (NK) cells
What is unique about NK cells? (***Boards***)
They are not part of adaptive or acquired immunity; they are part of innate immunity
What cells mature entirely in the bone marrow?
B lymphocytes and NK Cells
At what stage do you get of self-reactive B cells?
The immature B cell stage
(Express only IgM, rather than a mature, which expresses IgM and IgD)
What do activated B cells give rise to?
Plasma and Memory Cells
Maturation process of T lymphocytes
Leave the bone marrow as prothymocytes (prolymphocyte)
Arrive at Thymus, where they mature/differentiate into T lymphocyte subsets
***If they’re lucky (95-98% of prothymocytes die in the thymus because they’re self-reactive or they recognize someeone else’s MHC)
From there, they go out and populate lymphoid organs
What are platelets?
Anuclear cytoplasmis remnants of megakaryocytes
Play a role in hemostasis
What is endomitosis and what stimulates this process?
Endomitosis is the process by which Megakaryocytes undergo cytoplasmis divisions without cell division; can become a large polyploid (32N) cell
Thrombopoietin is a cytokine that stimulates endomitosis and production of thrombocytes (aka platelets)
How do Megakaryocytes produce platelets?
They form long cytoplasmic extension which constrict at various points and divide into fragments
(100-1000 platelets per Megakaryocyte)
Platlets
- Lifespan
- Where are they phagocytized when they die?
- Emergency reserve of platelets is located…
- Lifespan: 9 days
- Death: Liver or Spleen
- Emergency Reserve: Spleen
What is an Absolute Cell Count?
It provides the Quantity of each cell type per unit volume
What is the Differential Count?
It is a Relative Count** and therefore gives the **PERCENTAGE (%) of each cell type
Can you look at Absolute Cell Count or Differential Count and conclude that a patient is normal?
No; you have to look at both
What type of cell accounts for the highest percentage of Bone Marrow cells?
Granulocytes
(Stem cells is the lowest)
(RBCs is the second highest, as they have a longer lifespan than granulocytes)
Who has higher RBC count between males and females?
Males (4.3 - 5.7)
vs.
Females (3.8 - 5.1)
What is a normal Reticulocyte count?
About 1% of your RBCs (0.5 - 1.5%)
