1) Hematopoiesis Flashcards
hematopoiesis
process of blood cell production and development
categories of wbcs
- Granulocytes: Neutrophils, Eosinophils, Basophils
- Lymphocytes: T cells, B cells, Natural Killer cells
- Monocytes (and macrophages)
organs of the hematopoietic system
- bone marrow
- liver
- spleen
- thymus
- lymph nodes
- RES (MPS)
The hematopoietic system is able to respond to …. by increasing production of the cell type needed.
infection, bleeding or hypoxia
hematopoiesis does not occur in the…
RES (MPS)
lymph nodes
————– in which the development of the hematopoietic cells takes place lie just outside the marrow sinuses.
Hematopoietic cords
structure of marrow:
Several sinuses combine in a ————-, forming a —————- that enters the systemic circulation.
collecting sinus
central vein
function of thymus
serves as a compartment for maturation of T lymphocytes
The liver is not as effective as the spleen in…
filtering abnormal erythrocytes
because of rapid flow of blood past hepatic macrophages
cleans most of the particulate matter from the blood
liver
discriminating blood filter
spleen
spleen receives —% of cardiac output
5
2 spleen pathways
closed path (rapid)
open path (slow)
How does the open path in the spleen elimintate weak RBCs?
the hypoxic, acidic and hypoglycemic environment allows only the strongest cells to survive
5 functions of spleen
- culling
- pitting
- immune defense
- platelet storage
- extramedullary hematopoiesis
culling
removing old/damaged RBCs
pitting
plucking out inclusions from RBCs
pitting results in…
spherocytes
spleen’s immune function most important in…
young children developing immunity
—- of platelets are stored in spleen
damage causes…
splenomegaly causes…
1/3
increased PLT ct
decreased PLT ct
MPS
mononuclear phagocyte system (RES)
fixed macrophages are found in…
marrow
liver
spleen
lymph nodes
lungs
functions of monos/macros
- phagocytosis
- presentation to T-cells
- secretion of growth factors
Embryonic blood cells, excluding lymphocytes, originate from the…
mesenchymal tissue that arises from the embryonic germ layer, the mesoderm
sites of blood cell development in fetus
- Mesoblastic (mesoderm of yolk sac)
- Hepatic—starting at 2 months gestation
- Medullary—starting at 7 months gestation
- Extramedullary—if need for cells is great
primitive erythropoiesis
production of large erythroid cells in mesoderm of yolk sac
Platelets appear at — months gestation, and granulocytes at — months
3
5
As the child grows, long bone marrow is replaced with…
yellow marrow (fat cells)
By age 18-20, hematopoiesis occurs in the…
axial skeleton (skull, vertebrae, ribs, sternum, pelvis)
precursor cells are directed by ———-
cytokines
proliferation
rapid cell reproduction
differentiation
appearance of different capabilities in cells that were originally the same
commitment
the instance when a cell takes on a specific route of development
maturation
development of a cell from the “committed” stage to the fully mature stage at which the cell has all of its characteristics
3 compartments of hematopoietic cells
- Hematopoietic Stem Cells (HSC)
- Progenitor Cells
- Maturing Cells
0.5% of total immature hematopoietic cells
HSC
20,000 total
pluripotential cells capable of giving rise to all lineages of hematopoietic cells
HSC
HSC marker
CD34
3 fates of HSC
- self-renewal (make exact replica of itself)
- differentiation (develop into cell with different capabilities)
- apoptosis (cell death)
cannot self-renew, but they are capable of differentiation
progenitor cells
3% of the total immature hematopoietic cell population
progenitor cells
3 types of progenitor cells
Multipotential Progenitor Cell (MPP)
Common Myeloid Progenitor (CMP)
Common Lymphoid Progenitor (CLP)
A cell that is going to differentiate (not self renew), but is not committed to any specific cell line yet.
multipotential progenitor cell (MPP)
The youngest cell that is committed to differentiating into one of the following cell lines:
Granulocyte
Erythrocyte (RBC)
Monocyte
Megakaryocyte (platelet)
common myeloid progenitor (CMP)
The youngest cell that is committed to differentiating into a lymphocyte.
common lymphoid progenitor (CLP)
The cells of this group are committed to ONE cell line. They are morphologically identifiable.
maturing cells
95% of the total immature
hematopoietic cell pool
maturing cells
-blast
earliest maturing cell
soluble mediators that control hematopoiesis
growth factors (GF) or colony stimulating factors (CSF)
an interleukin number is assigned when…
AA sequence is defined
functions of GFs
- suppress apoptosis
- promote proliferation
- control and regulate differentiation
- enhance functional activity of terminally differentiated progeny of precursor cells
most GFs are produced by…
stromal cells (monocytes, macrophages, activated T lymphocytes, fibroblasts, endothelial cells, osteoblasts,
adipocytes)
EPO is induced by…
hypoxia
EPO mainly affects…
CFU-E
most GFs are ———-
glycoproteins
2 ways for GFs to stimulate hematopoiesis
- directly – binds to the target cell’s receptor & induces the response on that cell
- indirectly – binds to receptor on accessory cell & induces release of another cytokine that acts directly on the target cell (example: IL-1)
GFs that affect predominantly 1 lineage
lineage-restricted
GFs that influence activity of a wide spectrum of progenitor cells
multilineage
At the —— stage, the cells develop the Rh antigens and erythropoietin receptors.
CFU-E
GFs that inhibit cellular proliferation
negative regulators
examples of negative regulators
TGF-β (transforming growth factor-β)
TNF-α (tumor necrosis factor-α)
prostaglandins (E series)
SCI (stem cell inhibitor)
Procrit
Synthetic EPO. Stimulation of erythropoiesis in renal disease or after chemotherapy.
Neupogen
Recovery from treatment induced myelosuppression (to accelerate bone marrow recovery after intense chemo or radiation therapy).
G-CSF and GM-CSF.
erythropoietic island
central macrophage surrounded by nucleated red blood cells (taking iron)
progeny of CLP
- CFU-B
- CFU-TNK
- Dendritic cell
progeny of CMP
CFU-GEMM