Bone marrow Flashcards
Where is bone marrow
In the space between the cortex of bones
Traversed by bone trabeculae and blood vessels
Ribs, skull, vertebrae, and pelvic girdle, etc
Bone marrow function
Site of origin, maturation, and development of all peripheral blood cells
Lymphocytes are formed here, so it is classified as a primary lymphoid tissue
Hematopoiesis for:
- White blood cells (granulocytes, monocytes, lymphocytes)
- Red blood cells
- Platelets
- Granulopoiesis (neutrophil, eosinophil, basophil, mast cell), monocytopoiesis (monocytes, macrophages, DCs), lymphopoiesis (T cells, B cells, NK cells)
- Erythropoiesis
- Thrombopoiesis
Sites of hematopoiesis with age
Fetus: 0-2 months in yolk sac, 2-7 months in liver and spleen, 5-7 months in bone marrow
Infants: bone marrow, practically all bones
Adults: vertebrae, ribs, sternum, skull, sacrum, pelvis, and end of femurs
3 basic components of the bone marrow
Stem cells
Bone marrow microenvironment
Hematopoietic growth factors
Stem cells
Arise from yolk sac
Self renewable
Multilineage differentiation potential
Bone marrow microenvironment
- ECM
- Stromal cells
- ECM: attachment of progenitor cells or stem cells
- Stromal cells: physical support for hematopoietic cells, produce hematopoietic growth factors and express adhesion molecules that influence differentiation, ex: macrophages, fibroblasts, endothelial, etc
Stem cells express cell surface adhesion molecules to attach with specific structure in the ECM
Hematopoietic growth factors produced by stromal cells are presented to immobilized stem cells
Hematopoietic growth factors
Glycoproteins that act at low concentrations
Produced by many cells: stromal cells, monocytes, lymphocytes
May effect more than one lineage, or could be specific for 1
Active on stem cells and/or functional differentiated cells
Show synergistic or additive action with other growth factors
May have multiple actions
How to extract bone marrow
Take it from the iliac crest
Need two needles: one to break through the cortical bone and aspirate, and a second larger hollow Boar needed to extract the tissue
Erythropoiesis
Key factors: erythropoietin, GM-CSF, IL-3, IL-11
Maturation characteristics: nuclear condensation with ultimate extrusion of the nucleus, change of cytoplasm from deep basophilic, organelle rich substance, to a cytoplasm that consists almost entirely of hemoglobin
Rate: 3-4x10^9 cell/kh/day
Live 120 days
At the beginning the precursors have a lot of mRNA - will stain one colour
Later on they have a lot of hemoglobin and that will stain with eosin 1 - shift in colour from deep blue to purplish pink
Erythropoiesis morphological changes
Cytoplasm changes from blue to orange (decrease in RNA, increase in hemoglobin)
Nucleus becomes smaller (chromatin pattern more compact than expelled out of the cells)
5 stages of erythropoiesis
- Proerythroblast
- Basophilic erythroblast
- Polychromatic erythroblasts
- Orthochromatic erythroblasts
- Nuclear expulsion
Erythroid island
Macrophages store iron to give to the RBC precursors They also phagocytose the extruded nuclei
So they have to be in the islands
Erythropoietin
Erythropoietin made in the kidney
If there is less O2 flowing into the kidney it will activate cells and they will produce it
Find its way to marrow and stimulates precursors to enhance production of red cells
The reticulocytes will get pushed out to try to compensate for sudden anemia
Will take 5 days, so wont see results of increasing production until then
Thrombopoiesis
Key factors: thrombopoietin, GM-CSF, IL-3/6, EPO
Maturation characteristics: increase size and DNA content, nuclear division without cell division, increase nuclear lobulations, development of demarcation membranes and cytoplasmic granules, platelet release
Platelets survive 10 days