Flashcards in 2 - Hematopoiesis Deck (39):
“formation of blood cells”
functions of Hematopoiesis
- Provides the cellular elements (RBC’s and leukocytes) of the peripheral blood; takes place in the bone marrow.
- Delivery of oxygen to the tissues + providing host cell defense
- Replaces of 0.5 X 10^12 cells/day
Hematopoiesis tightly controlled due to
- distinct cell lifespans
distinct cell lifespans
Lymphocytes – years
--- if now a memory cell may live very long
RBC’s – 120 days
Platelets – 7 to 10 days
Granulocytes – 6 to 8 hours
Neutrophils may be several days actually but some of the shortest lived cells so need to be replaced often.
Characteristics of hematopoietic stem cells
0.1 - 0.01% of bone marrow cells
Give rise to progenitor cells of all lineages
Highest proliferative potential of any hematopoietic cell type
Capable of self-renewal and differentiation
Can’t be identified morphologically
two things needed if cell is going to differentiate in the bone marrow
- cell to cell contact with bone marrow stromal cells
--- tell the cells what to become
--- Drive specific cell differentiation pathways
bone marrow stromal cells play role in
Important role in maintenance + differentiation of hematopoietic cells
--- Microenvironment for differentiation
examples of bone marrow stromal cells
adipocytes, fibroblastoid cells and reticuloendothelial cells
characteristics of adipocytes, fibroblastoid cells and reticuloendothelial cells
- Stem cells/primitive precursors bind firmly
- Maturing precursor cells nonadherent
- Differential expression of cell adhesion molecules regulates the binding activity
- Progenitor cell cytokines
- End-stage cytokines
Progenitor cell cytokines
- e.g. stem cell factor,
- act on immature cells
- act on more differentiated cell types to induce lineage-specific differentiation
- ex/ granulocyte colony stimulating factor (G-CSF), IL-2, IL-7, etc
- Granulocyte colony stimulating factor (G-CSF)
- released by macrophages at inflammatory sites → circulates to bone marrow → production/release of neutrophils
- produced/released by peritubular interstitial cells (kidney) in response to hypoxia.
- EPO circulates to bone marrow → production and release of RBC’s.
- ↑ oxygen pressure inhibits production of EPO.
--- feedback mechanism
- ez/ of inhibitory cytokine
- Downregulation of stem cell growth/differentiation by TGF-B by ↓ cell surface receptors for growth/differentiation cytokines
clinical utility of cytokines: G-CSF
- BMT – mobilizes stem cells to blood. Harvesting less invasive than bone marrow and ↓ chance of contaminating tumor cells.
- Stimulates granulopoiesis following chemotherapy-induced marrow suppression → ↓ chance of infection + more frequent chemotherapy
clinical utility of cytokines: GM-CSF
- ↑ myeloid cell recovery in bone marrow transplantation patients
- More toxic than G-CSF → thrombosis and capillary leak syndrome
--- not used as often
clinical utility of cytokines: EPO
Anemia as a result of renal insufficiency → increases RBC mass
bone marrow forms
- Yellow marrow - normally inactive and mainly adipose tissue
- Red marrow - active in hematopoiesis
locations of marrow
- First few years of life → all marrow is red
- By age 18, red marrow is found in ribs, sternum and pelvis
- when demand exceeds capacity of bone marrow
- takes place in spleen and liver when bone marrow dysfunctional or unable to meet the demands on it
*maturational characteristics - Erythropoiesis
As a cell matures:
1. Cell size ↓
2. Nuclear:cytoplasmic ratio ↓
3. Nucleoli ↓ in number and eventually disappear
4. Cytoplasmic staining → darker blue to lighter blue ↓ RNA
- every single lineage will share these characteristics
What is Erythropoiesis?
The formation or production of RBC’s
- Starts: primitive RBC's in the embryonic yolk sac
- Continues: extramedullary organs (i.e. liver, spleen)
- Predominates in the red marrow during late fetal development
- reticulocyte is young erythrocyte
What is granulopoiesis?
Production of cells in the granulocytic lineage, including neutrophils, eosinophils and basophils
immature form of granulocytes
- band cells
--- can be released on own from bone marrow
--- can be neutrophilic, eosinophilic, basophilic
--- will mature in periphery
*- ↑ % of band forms in the blood termed "shift to the left".
--- generally refers to neutrophils
- After release granulocytes circulate for a few hours and then die.
- In circulation, neutrophils evenly distributed between (1) circulating and (2) marginating pools (loosely attached to endothelial cells). Dynamic equilibrium maintained between two pools.
- Splenic phagocytes remove dead/dying granulocytes from circulation.
names of monocytes-macrophages
Macrophages develop from monocytes and are distributed throughout the body with name being dependent upon location of the cells.
--- Histiocytes - loose connective tissues
--- Kupffer cells - liver
--- Osteoclasts - bone
--- Microglial cells - nervous system
- Monocytes circulate for approximately 8 hours, then enter the tissues to differentiate into macrophages.
- Macrophages lifespan is from months to years.
What is lymphopoiesis?
Production of cells in lymphocytic lineage, including T lymphocytes, B lymphocytes or natural killer (NK) cells
--- B lymphocytes and NK cells → develop entirely in the bone marrow and are released into the peripheral blood
-----> selection against self-reactive B-cells
--- B and T = humoral immunity
--- NK = innate immunity
T lymphocyte maturation sequence:
- In the bone marrow until prothymocytes (“prolymphocyte”) are released into peripheral blood to migrate to the thymus
- Once in thymus, termed thymocytes
- Within thymus → mature/differentiate into T lymphocyte subsets
- Most thymocytes die in the thymus (positive and negative selection)
--- 95-98% cells die
- Once T lymphocytes leave thymus, most populate lymphatic organs
What is Thrombopoiesis?
- The production of platelets (a.k.a. “thrombocytes”)
- Anuclear cytoplasmic remnants of megakaryocytes
- Role in hemostasis → limit bleeding, repair endothelium
- Megakaryocytes undergo endomitosis (nuclear mitosis without cytoplasmic divisions) → large polyploid (32N) cell
--- platelets are fragments of megakaryocytes
- stimulated by thrombopoietin
- stimulates thrombopoiesis
- Promotes megakaryocyte precursor production
- Stimulates endomitosis
--- act like they're going to divide (cytoplasm) but don't actually divide
- Long cytoplasmic extensions which constrict at various points and divide into fragments
- Each megakaryocyte → 100 – 1000 platelets
- small and anuclear
- Lifespan = ~ 9 days
- Death → platelet is phagocytized in liver or spleen
- Emergency reserve of platelets in the spleen
normal values: absolute cell count
- provides the quantity of each cell type per unit volume.
- E.g. 4.5 - 11.0 X 10³ WBC's/mm³ (also seen as ul).
- Absolute cell count for a cell type = Total WBC count X % cell type
normal values: differential count
relative count; gives the % of each cell type
most common cell type in bone marrow
granulocytes (b/c shorter lifespan, have to make more)