Lecture 2 Flashcards
Hematopoiesis
process through which formed elements of the blood are produced
Vital role in these are:
Erythrocytes
Leukocytes
Platelets
erythrocytes: gas exchange
leukocytes: immunity
platelets: clotting disorders
Explain the formation of erythrocytes and leukocytes in several organs before their differentiation in the bone marrow
- yolk sac phase: hematopoiesis begins in the 3rd week of gestation formation of “blood islands”
- hepatic phase: major blood forming organ in second trimester; (and the spleen)
- bone marrow phase: begins during second trimester as well (also involves other lymphatic tissue)
Hematopoietic stem cells can differentiate into….
skeletal muscle
cardiac muscle
neurons, glia
liver cells
Bone marrow stromal cells can differentiate into…
skeletal muscle
cardiac muscle
Neural stem cells can differentiate into….
skeletal muscle
blood cells
Def. Totipotent
all embryonic tissue
i.e- morula
Def. Pluripotent
all adult tissue cells
i.e- inner cell mass
Def. Multipotent
small # of cells
Def. Unipotent
only 1 cell type
- Def. Hematopoietic Stem Cells
- Where are they found?
in bone marrow, give rise to multiple colonies of progenitor stem cells
Cavity of long and axial bones (epiphyseal plate- spongy or cancellous bone). They are surrounded by stroma (mesenchymal origin) and give rise to:
- fibroblasts
- adipocytes
- endothelial cells
- osteoblasts *closely associated with stem cells as they regulate number and fate of HSCs in that specific niche and they are necessary to produce cytokines
Def. Progenitor Stem Cells
(CMP) common myeloid progenitor
-G E M M- granulocytes, erythrocytes, monocytes, megakaryocytes
(CLP) common lymphoid progenitor
-T- cells, B- cells, NK cells
Stem cell vs. Progenitor Cell
Stem cell yields a copy of itself and a specialized cell
Progenitor cells yield two specialized cells
stem cell niche
spatial structure (microenvironment) in which HSCs are housed an maintained by allowing self-renewal in the absence of differentiation
- storage
- self-renewal
- no differentiation
vascular niche
inactive HSCs migrate to the center of bone into this area to establish hematopoiesis
- endothelial cells, fibroblasts and adipocytes are all found here
- supports and promotes differentiation and progenitors into formed elements of blood
- *stromal cells secrete growth factors (glycoproteins) here
What are the growth factors secreted by stromal cells in the vascular niche? (progenitor cells have surface receptors)
- EPO: (kindeys) increase erythrocyte precursors
- TPO: (liver) stimulates thrombocyte formation
- Cytokines: (bone marrow) stimulate proliferation in other marrow cells.
- Colony-stimulating factor (CSF) and Interleukin stimulate leukocyte production
Explain the structure of bone marrow
- Loose cells of reticular fibers
- sinusoidal capillaries in bone marrow to allow spaces between endothelial cells
- veins
- arteries
- islands of cells
red marrow vs yellow marrow
red: active hematopoiesis
yellow: inactive hematopoiesis; fat, capillaries, reticular cells
Erythropoiesis.
Where does it take place?
Main stimulus?
Precursor?
- adult red bone marrow of certain bones
- Hypoxia
- Proerythroblast
End Stage Kidney Disease.
decrease EPO
decrease RBCs
reduced Oxygen
Explain cycle of erythropoiesis stimulation.
- Hypoxia due to a decrease in RBC count
- decrease in O2 in the blood and increased demand of oxygen in the tissues
- kidneys release EPO
- EPO stimulates red bone marrow
- increase in RBC count
- increase in the ability of RBC to carry blood
Granulocytopoiesis
Controlled by?
Common precursor?
takes 11 days
Neutrophils
Eosinophils
Basophils
- controlled by cytokines
- precursor: myeloblast
*myelocyte: condensed, round nucleus; specific granules; in this phase depending what they contain determines what they become
Thrombopoiesis
Controlled by?
formation of thrombocytes (platelets)
-controlled by thrombopoietin in the liver
- megakaryoblast: 25-40 um (32 nuclear)
- megakaroycyte: 40-100 um (large, multi-lobed nuc)
Lymphopoiesis
lymphoblasts: large, undifferentiated cells
pro lymphocytes: medium sized cells, condensing chromatin, no cell surface antigens
- some migrate from bone marrow to thymus to differentiate and divide into T-cells
- others remain in bone marrow to differentiate to B-cells, migrate to lymph nodes
Mast cells
made in the bone marrow but migrate to the CT to differentiate
When are bone marrow studies done?
- prolonged fever
- anemia
- bleeding disorders
*sample taken from iliac crest
Leukemia
no WBCs being made in the bone marrow
Aplastic anemia
no RBC being made in the bone marrow