Hematopoiesis Flashcards
Neutropenia
Not enough neutrophils (happens after chemo, bone marrow transplant)
2 options: use G-CSF or GM-CSF
Better: G-CSF (b/c better outcome)
3 types of granulocytes
BEN
Basophil, eosinophil, neutrophils
Eosinophil
Treat parasites
Reduce severity of allergic rxns
Basophils (least common)
Big, dark stained granules
Heparin (prevent clots) and Histamine(promotes blood flow to tissues), kallikrein (attracts eosinophils)
Role in hypersensitivity reactions
Neutrophils
Most common granulocyte
Antimicrobial
Inflammation (pus)
Role in phagocytosis of bacteria/dead cells
Thrombopoesis
Making platelets
endomitosis–>megakaryocyte–>chopped up into platelets
Regulated by thrombopoietin
Thrombopoietin
Made in liver, stim. development of megakaryocyte
Deficiency in thrombopoietin leads to what?
Thrombocytopenia (low platelet count)
This leads–>idiopathic thrombocytopenic purpura(ITP)
Signs of “Idiopathic Thrombocytopenic Purpura(ITP)
Bruising
not enough platelets
Excess thrombopoietin=
Thrombocytosis
Stem cell facto (SCF) i.e. “c-kit ligand”
Made by fetal tissues
Increases responsiveness of stem cells to cytokines
Potential uses: for hematopoiesis and bone marrow transplants
HGF’s: hematipoietic growth factor (3)
- Colony stimulating factor (CSF)
- Erythropoietin and thrombopoietin (stim platelet production)
- Cytokines (interleukins)
Erythroid lineage (aka RBC)
“CFUs Produce Blood Precursors Of Reticulocytes & Erythrocytes
Pluripotent stem cell–>myeloid progenitor–>erythroid CFU–>mature progenitor–>
Proerythroblast–>basophilic erythroblast–>polychromatophilic erythroblast–>orthochromatic erythroblast–>reticulocyte–>erythrocyte
*=where EPO can stimulate
What leads to upregulating production of RBC’s and what can do this?
- Hypoxia
- Loss of blood
Using Erythropoietin (EPO)
Erythropoietin (EPO)
Made in kidneys (90%)
Stimulates progenitor cells–>turns off inhibitors & increases cyclins and antiapoptotic proteins (Lance Armstrong)
Leukopoiesis
Making of WBC
CSF
(CSF=colony stimulating factor)–>stimulates CFUs (colony forming units)
-speeds up neutrophil development
Hematopoietic progenitor cells (HPCs)
Can be moved to blood by chemotherapeutic drugs and hematopoietic growth factors
Hematopoiesis is regulated by what 2 factors?
Hematopoietic stem cells (HSCs) and Hematopoietic progenitor cells (HPCs)
Islands in bone marrow
Make blood cells and when done go into vein channels–>circulation
Vascular niche
Where most of bone marrow is (center of long bone)
Marrow, stromal compartment
holds everything together
Endosteal niche
Inner layer of bone (osteoblastic niche)
Area between bone and marrow
Have osteoblasts (make) and osteoclasts (Break)
Where is the long-term storage of quiescent HSC’s?
Endosteal niche
Niches
Differentiation occurs here. Will call in quiescent (parked) cell and make needed cells
Give physical support, allow signals inside
Endothelial cells
Gatekeeper
Make growth factors and cytokines
Allows mature cells out
Macrophages
Vacuum cleaners
Osteoblasts
Make angiopoietin 1-upregulate differentiation
Thrombopoietin: neg regulator
Osteopontin
Helps osteoblasts but negative effects on # of hematopoietic stem cells
Types of Cells
Hematopoietic stem cells: can self-renewal (need to look at cell surface markers to identify)
Committed precursor cells: make myeloid or lymphoid
Maturing cells: come from committed precursor cells
Erythroid CFU (colony forming unit)–>
RBC
Megakaryote CFU (colony forming unit)–>
Platelet
Granulocyte-macrophage CFU (colony forming unit)–>
Monocytes and neutrophils
Basophil CFU (colony forming unit)–>
basophil
Eosinophil CFU (colony forming unit)–>
eosinophil
Lymphoid stem cell–>
T and B cells
Why use CFU’s? (colony forming unit)
Allows body more specificity
You can have specific things that act on these units
