Hematopoiesis Flashcards
(38 cards)
Where does hematopoiesis occur and what are they derived from?
Skull, sternum, ribs, vertebrae, pelvis and proximal femur, derived from hemopoietic stem cells
What two lineages come from hemopoietic stem cells?
Common lymphoid progentior CLP and common myeloid progenitor CMP
Where does hematopoiesis start during 1st trimester of development?
In yolk sac/umbilical vesicle, developed from hemangioblasts
Where does hematopoiesis continue during 2nd trimester and 7th month?
2nd trimester occurs in liver and then spleen, 7th month occurs in bone marrow
What are the main constituents of bone marrow?
Blood vessels, hematopoeitic cells, and sinusoids
Bone marrow has endothelial lining, discontinuous basement membrane and adventitial cells, what are these and what do they produce?
They are cells that provide support for developing blood cells and produce reticular fibers and cytokines
What lies in between sinusoids and what do sinusoids do in bone marrow?
They separate hematopoietic compartment and peripheral circulation, with cords in between
What are the first two steps for the bone marrow-sinusoidal system (new blood cells penetrating endothelium to enter blood circulation)? (2)
- Maturing blood cell/megakaryocyte process pushes against endothelial cell
- Fuses and pierce luminal plasma membrane (endothelial cell) forming a transitory opening
What occurs once a blood cell forms a transitory opening in an endothelial cell to enter the blood stream from a sinusoid in bone marrow? (2)
- Each blood cell/process squeezes through and enters sinusoidal lumen
- Endothelia cell repairs itselft and the opening closes (WHOLE PROCESS CALLED A TRANSCELLULAR EVENT)
What is special about red bone marrow (4)?
located in medullary cavity of young long bones/spongy
Hematopoietic cords are developing blood cells/megakaryocytes
Contains macrophages, mast cells and adipose cells
specific blood cells develp in their own nests/clusters
What is special about yellow bone marrow (4)?
Mainly adipose tissue
located in medullary cavity of adult bones (not active bone marrow)
In active bone marrow, you will see 50% adipose/50% hematopoietic tissue
Can always return to being red bone marrow
how do you calculate normal cellularity of bone marrow (ratio of hematopoietic cells to adipocytes)?
subtract individuals age from 100 and add -/+10%
What is the difference between hypo and hypercellular marrow?
Hypo: few blood forming cells found (like chemo)
Hyper: BM affected by hematopoietic cell tumors (leukemia)
What is the difference between a bone marrow aspirate and core biopsy?
Aspirate is not always accurate, mainly cells where core biposy scrapes bone and able to analyze bone architecture **better analyzation
How are hematopoietic stem cells regulated (3) and what produces the regulation (5)?
Regulated by
colony-stimulating factors (CSF)
Erythropoeitin (EPO) and Thrombopoietin (TPO)
Interleukins (cytokines) IL-3 IL-2 IL-6 etc
Endothelial, stromal, fibroblasts, lymphocytes, and macrophages produce these 3 groups
What do CMP and CLP express on their surface receptors and lineage restricted progenitors are derived from CMPs (common myeloid progenitor cells)?
Their receptors influence proliferation and maturation, as well as contain cytokines and colonystimulating factors CSFs
CMPs become granulocyte/monocyte progenitors (GMP) and megakaryocyte/erythrocyte progenitor (MEP/ErP)
What cells are derived from GMPs (granulocyte/monocyte progenitor)?
Neutrophil progenitors
Eosinophil progenitors
Basophil progentiors
Monocyte progenitors
What regulates erythropoiesis and what ‘influences’ or directs MEP->ErP?
Regulated by erythropoietin (EPO) acts on surface receptors ErP
EPO, IL-3, and IL-4 direct MEP to become ErP/CFU colony forming unit, then GATA-1 is needed
What are the first two steps of erythropoeisis?
- ErPs become proerythroblasts, large spherical nucleus & cell, dark purple cytoplasm
- Proerythroblast becomes basophilic erythroblast, small nucleus, dark purple staining d/t lots of Hg
What are the last 3 steps of erythropoiesis after proerythroblast is formed?
- Polychromatophilic erythroblast: acidophilic+basophilic/purple+pink stain cytoplasm, smaller nucleus
- Orthochromatophilic erythroblast (normoblast), acidophilic cytoplasm and dense nucleus, large than mature erythroblasts, **start to lose nucleus
- Polychromatophilic erythrocyte = reticulocyte, increased when high loss of blood, light purple stain no nucleus
What regulates thrombopoiesis and what does the process make?
It makes platelets/ megakaryocytes for clotting, regulated by GM-CSF and IL-3 TPO growth factors to become MKP (progenitor) forms megakaryocyte (large nucleus and size)
What are the steps for megakaryocyte to get into the blood in order to start platelet formation?
Thrombopoietin (TPO) produce in liver and kidney
- MKC too large cannot get to blood
- extends protoplatelets through opening in endothelia cells
- Platelet peirces through, breaking off when colliding with other things in circulation; go to site needed
What is granulopoiesis, what growth factors make GMPs into NoP, EoP, and BaPs?
Granulopoiesis is the formation of neutrophils, basophils, monocytes, and eosinophils. Granulocyte/monocyte progenitor (GMP) use GM-CSF (colony stimulating factor) to make N/E/B progenitors
What is special about eosinophil and basophil progenitors compared to neutrophil progentiros?
E and B have 6 steps, but only four are identifiable. E requres GM-CSF, IL3, and IL5m while B requires GM-CSF and IL3
