Hematopoiesis Flashcards
hematopoiesis
formation and development of blood cells
The hematopoietic system
lymph nodes
- thymus
- liver
- spleen
- bone marrow
three phases of hematopoiesis
- mesoblastic phase (2-12 wks): blood islands from primitive erythroblasts
- hepatic phase (5 wks to birth):
- liver is major site of hematopoiesis during 2nd trimester
- spleen, kidney, thymus and lymph nodes also
- granulocytes, monocytes, lymphocytes, and megakaryocytes appear - medullary phase (5 mos to remainder of life):
- bone marrow takes over production
- major site by wk 24
T or F. Active bone marrow decreases as we age
T!
Estimated BM cellularity: 100 - age (+/- 10%)
requirements for hematopoiesis
- adequate micro-environment (stroma)
- hematopoietic stem cells
- nutrients (iron, vitamin B12, folate)
- hematopoietic growth factors and cytokines
- feedback inhibition mechanisms
Stromal cells include (7)
- endothelial cells: control flow of particles entering/leaving
- macrophages: phagocytosis, secrete cytokines/growth factors
- osteoblasts: bone-forming cells
- osteoclasts: bone-resorbing cells
- fibroblasts: form supporting lattice, secrete extracellular matrix
- adipocytes: fat cells, secrete cytokines/growth factors
- lymphocytes: cytokines/growth factors
- critical role in the regulation of hematopoietic stem cells
Hematopoietic Stem Cells (HSCs)
- capable of self renewal
- pluripotent
- can give rise to differentiated progeny
- are able to reconstitute the hematopoietic system of lethally irradiated host
- 3 fates: self-renewal, differentiation, apoptosis
hematopoietic growth factors and cytokines
- regulate proliferation, differentiation, and maturation of hematopoietic precursor cells (method of INTERcellular communication
- may exert a positive or negative effect on proliferation
- prevent apoptosis of precursor cells
- includes CSF (colony stimulating factors), IL, and chemokines + interferons
glycoprotein hormone produced in the renal peritubular interstitial cells
EPO (erythropoietin)
EPO
- stimulates proliferation of committed erythroid cells
- regulates rate of erythropoiesis: early release of reticulocytes from bone marrow, prevents apoptosis for RBC precursors, reduces time needed for RBC precursors to mature
- induces hemoglobin synthesis
nutritional requirements for erythropoiesis
- protein and amino acids: building blocks of Hb
- vitamin B12 and folic acid: DNA synthesis
- vitamin B6 (pyridoxine): heme synthesis
- vitamin C: iron absorption
- iron: hemoglobin synthesis & cell proliferation
- copper: intracellular iron utilization
- cobalt: component of vitamin B12
Erythropoiesis summary
occurs with maturation:
- decrease in cell size
- condensation of nuclear chromatin
- loss of nucleoli
- decrease in N:C ratio
- decrease in RNA and mitochondria
- increase in Hb
Granulopoiesis summary
with maturation:
- decrease in size
- condensation of nuclear chromatin
- change in nuclear shape
- change in cytoplasm colour
- appearance and disappearance of primary granules
- appearance of secondary granules
platelets are derived from megakaryocytes in a process called
endomitosis
- nucleus is duplicated but no cell division occurs
- polyploid cell
- cytoplasm of megakaryocytes becomes platelets
Granulopoiesis pools (3) of developing cells in bone marrow
- stem cell pool: HSCs (self-renewing)
- proliferation pool: CMP, GMP, myeloblasts, promyelocytes, myelocytes
- maturation pool: metamyelocytes, bands, segmented granulocytes
Granulopoiesis pools (2) of developing cells outside bone marrow
- circulating pool (blood)
- marginating pool (tissues or on capillary walls)
after cells have matured, can migrate between these pools
in late stage of this stage of erythropoiesis, nucleus is ejected and engulfed by macrophages
orthochromic normoblast
- chromatin is completely condensed = pyknotic
