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