Lecture 15: Hematopoesis Flashcards Preview

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Flashcards in Lecture 15: Hematopoesis Deck (18)
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Give some basic characteristics of stem cells

- May proliferate extremely well
- Self-renewing
- May differentiate into several (at least 2) different cell-types
- May reconstitute tissues after injury


Describe the 3 hierarchies of stem cells pertaining to developmental capacity

- Totipotent: Totipotent cells give rise to all cells of an organism, including embryonic and extraembryonic tissues (cells which support embryonic development). A zygote is totipotent.
- Pluripotent: Pluripotent cells give rise to all cells of the embryo and subsequently adult tissues. (embryonic stem cells).
- Multipotent: Multipotent cells give rise to different cell types of a given lineage. (adult stem cells).


What are the two types of stem cells

* Embryonic Stem Cells
- Derived from Inner-Cell Mass of blastocyst
- Pluripotent, differentiate to all cell lineages
- Technical and ethical limitations
- May be induced from adult tissues
* Adult Stem Cells
- Harvested from mature organs/tissues (bone marrow)
- Multipotent
- More restricted ability to produce different cell types and to self-renew


Describe the hematopoetic sites pertaining to gestation times

* 2-8 weeks of gestation:
- Islands of hematopoiesis (blood islands) are found in the yolk sac wall.
- Give rise to nucleated erythrocytes from 2-8 weeks of gestation.
- No leukocytes form during this phase.
* 8-28 weeks of gestation:
- Hematopoiesis first occurs in the liver and then the spleen.
- Normally ceases around the time of birth.
* 6 months gestation to birth and beyond:
- Hematopoiesis occurs in red bone marrow.
- See Slide 6


Describe the characteristics of bone marrow

- At birth, all the marrow is red marrow.
- Red marrow is the source of all blood cells.
-- Prior to puberty: Skull, ribs, sternum, vertebrae, clavicles, pelvis, long bones
--After puberty: As above except for long bones
- Extramedullary hematopoiesis: In certain disease states, blood cell formation may occur in liver and spleen.
- In time, most marrow is converted to yellow marrow, and red marrow is usually restricted to sternum and iliac crests (see text).


Give the histology of bone marrow

* Stroma:
- Contains fibroblasts, reticular cells, adipose cells, and endothelial cells.
- Synthesizes and secretes hematopoietic growth factors. •
* Parenchyma:
- Consists of various lineages of hematopoietic cells in different stages of differentiation.
* Sinusoids:
- Endothelial-lined spaces that connect arterial and venous vessels.
- Provides access for mature blood cells to move into the circulation.
* Hematopoietic cords:
- Bands of parenchyma and stroma lying between the sinusoids.


Describe the distribution of hematopoietic cells

* Total number of cells:
- 60% in granulocytopoiesis
- 30% in erythrocytopoiesis
- 10% in thrombocytopoiesis, monocytopoiesis, and lymphocytopoiesis
* Myeloid/erythroid ratio: Total volume of cells in granulocytopoiesis/Total volume of cells in erythrocytopoiesis

3:1 is normal
8:1 suggests leukemia
1:5 suggests polycythemia


Describe transendothelial migration

- Mature blood cells migrate from the hematopoietic cords through the sinusoidal endothelial walls into the sinusoids.
- Megakaryocytes (site of platelet production) are too large to translocate and must remain in the stroma.
- See slides 10-16


Describe hematopoietic stem cells

- Are pluripotential: Committed to either myeloid or lymphoid stem cell lines
- Can self-renew
- Produce two kinds of multipotential precursor cells:
-- Myeloid stem cell: Give rise to all blood cell lines except lymphocytes
-- Lymphoid stem cell: Give rise to lymphocytes
- Cannot be identified by morphology but can be recognized by cell surface markers


List everything leukocytes can break down into (or at least what's listed on slide 18)

1. Granulocytes: Neutrophils, eosinophils, basophils

2. Agranulocytes: Monocytes, Lymphocytes


Describe Myeloid Stem Cells:

Gives rise to five kinds of colony-forming units:

- Erythroid CFU: Derived from myeloid stem cell but produces red blood cells, not white blood cells
- Megakaryocyte CFU: Derived from myeloid stem cell but produces platelet-forming cells, not white blood cells
- Basophil CFU*
- Eosinophil CFU*
- Granulocyte-Macrophage CFU*
* = White Blood Cell
- See Slides 20-24


What two classes do lymphoid stem cells break down into

Give rise to two kinds of cell lines:
- T-cell progenitor: Matures in thymus
- B-cell progenitor Matures in bone marrow

T = Thymus, B = Bone Marrow, (But remember it says MATURE)


What is the maturation phases of a macrophage?
For a neutrophil?

Of an erythrocyte

- Monoblast*, Promonocyte, Monocyte**, Macrophage

- Myeloblast*, Promyelocyte*, Myelocyte*, Metamyelocyte, Band cell**, Neutrophil**

- Proerythroblast*, Basophilic erythroblast*, Polychromatophilic erythroblast*, Orthochromatic erythroblast, Reticulocyte**, Erythrocyte** (See Slide 36-41)

* Cells which can divide
** Cells normally found in circulation


What are the characteristics of hematopoietic growth factors?

- Hematopoietic growth factors and cytokines are produced by endothelial cells in the marrow, fibroblasts, and stromal cells.
- Glycoproteins
- Three major groups:
-- Colony –stimulating factors
-- Erythropoietin and thrombopoietin
-- Cytokines (primarily interleukins)


Describe colony-stimulating hematopoietic growth factors

* Granulocyte/monocyte colony-stimulating factor: (GM-CSF)
- Produced by endothelial cells, T cells, fibroblasts, and monocytes
- Stimulates granulocytopoiesis and monocytopoiesis
- Ameliorates neutropenia associated with chemotherapy or radiation therapy (synthetic form: sargramostim or melgramostim).
* Granulocyte colony stimulating factor (G-CSF):
- Produced by endothelial cells, fibroblasts, and macrophages
- Directs CFU-G to proliferate and differentiate into myeloblasts
- May be used following chemotherapy or radiation therapy to treat neutropenia
* Monocyte colony stimulating factor:
- Commits CFU-GM to monocytic pathway


Describe the hematopoietic growth factor categories: erythropoietin and thrombopoietin

* Erythropoietin:
- Directs CFU-E to proliferate and differentiate into proerythroblasts
- Produced in kidney in response to decrease in oxygen saturation
- Secondary polycythemia is any abnormal increase in total RBC mass resulting from hypoxia and stimulating release of erythropoietin.
-- Possible causes include Tetralogy of Fallot and cigarette smoke.
* Thrombopoietin:
- Directs formation of megakaryoblasts
- Produced in proximal convoluted tubules of kidney
- Produced in parenchymal cells and sinusoidal endothelial cells of liver
- No therapeutic use
- See Slide 47


Describe the hematopoietic growth factor, cytokines

* Cytokines (primarily interleukins):
- Mediate positive and negative effects on cellular quiescence, apoptosis, proliferation, and differentiation.
- Engage specific receptors and activate a variety of signaling pathways.
- Examples:
-- Interleukin-3
-- Fit-3 ligand
-- Kit ligand
- See Slide 49


What are the 2 other smaller categories of hemtopoietic growth factor regulators and describe each.

* ECM components:
- Heparin sulfates
- Collagens
- Laminin
- Fibronectin
* Chemokines:
- Regulate blood cell trafficking and homing to sites of need.
- May serve as positive and negative growth regulators.
- Bind to guanine protein-coupled transmembrane receptors.
- Example: Sdf-1