hematopoiesis

Question 1

Hematopoiesis defintion/functions

Answer 1

• Define = formation of blood cells
• Functions
  
  • provides the cellular elements (RBC’s and leukocytes) of the peripheral blood; takes place in the bone marrow
  • delivery of oxygen to the tissues + providing host cell defense

Question 2

Cell lifespans of differeing cells

Answer 2

• Granulocytes = 6-8 hours
  
  • neutrophils, eosinophils, basophils etc
  • most precursor cells (greater abundance than even red blood cell precursors)
• platelets = 7 to 10 days
• RBC = 120 days
• macrophages = months to years
• Lymphocytes = years
  
  • especially memory T cells

Question 3

Hematopoietic stem cells

Answer 3

• .1-.01% of bone marrow cells
• Give rise to progenitor cells of al llineages
• highest proliferative potential of any hematopoietic cell type
• capable of self-renewal and differentiation
• multipotential
• needs STROMAL CELLS AND CYTOKINES

Question 4

Bone marrow stromal Cells

Answer 4

• Important role in maintenance + differentiation of hematopoietic cells
  
  • examples = adipocytes, fibroblastoic cells and reticuloendothelials
• provide a microenviornment for differentiation
• stem cells/primative precurors bind FIRMLY to stromal cells (the younger the stronger the binding)
• Maturing precursor cells nonadherent (the older the cells, binding is less important)
• Differential expression of cell adhesion molecules regulates the binding activity

Question 5

Role of cytokines

Answer 5

• Induce lineage-specific differentiation
  
  • tell the cell what it needs to differentiate into
• DOWNREGULATION of stem cell growth/differentiation by TGF-Beta by DECREASE cell surface receptors for growth/differentiation cytokines
  
  • transforming growth factor beta = INHIBITS PRODUCTION OF CELLS (downregulates)

Question 6

G-CSF

Answer 6

1. G-CSF (granulocyte colony stimulating factor) released by macrophages at inflammatory sites
2. circulates to bone marrow
3. Production/release of NEUTROPHILS

Question 7

EPO

Answer 7

1. EPO produced/released by Peritubular interstitial cells (kidney) in response to hypoxia
2. EPO circulates to bone marrow
3. Production and release of RBC’s
4. Increase oxygen pressure inhibits production of EPO

Question 8

describe the clinical utility of cytokines

Answer 8

• G-CSF
  
  • stimulates granulopoiesis following chemotherapy-induced marrow suppression –> decrease change of infection + more frequent chemo
  • BMT - mobilizes stem cells to blood. harvesting less invasive than bone marrow and decrease change of contaminating tumor cells
• GM-CSF
  
  • Increase myeloid cell recovery in bone marrow transplantation patients
  • more toxic than G-CSF –> thombosis and capillary leak syndrome
• EPO
  
  • anemia as a result of renal insufficiency –> icnreases RBC mass

Question 9

Types of bone marrow

Answer 9

• Yellow marrow = normally INACTIVE and mainly adipose tissue
• Red Marrow = active in hematopoiesis
  
  • first few years of life = all marrow is red
  • by 18, red marrow is found in ribs sternum and pelvis

Question 10

extramedullary hematopoiesis

Answer 10

• takes place in spleen and liver when bone marrow dysfunctional or unable to meet the demands on it

Question 11

Maturational characteristics of erythropoiesis****

Answer 11

• As a cell matures
  
  • Cell size DECREASE
  • Nuclear: cytoplasmic ratio DECREASES (higher N:C ratio –> Lower N:C ratio)
  • Nucleoli DECREASE in number and eventually disappear
  • Cytoplasmic straining –> Darker blue to light blue (basophilic cytoplasm –> lighter cytoplasm)

Question 12

Define erythropoiesis

Answer 12

• Definition = foration or production of RBC
• Starts: primitive RBC in the embryonic yolk sac
• continues in extramedullary organs (liver, spleen)
• Predominates in the red marrow during late fetal development

Maturation sequence: Stem cell –> rubriblast –> prorubricyte –> rubricyte –> metarubricyte –> reticulocyte –> mature erythrocyte

Question 13

Granulopoiesis

Answer 13

* define: production of cell in the granulocytic lineage, including neutrophils, eosinophils and basophils

Sequence: stem cell –> myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> BAND –> granulocyte

• BAND CELL = almost, but not quite granulocyte…
• In circualtionm neutrophils evenly distributed between circulating and marginating pools (dynamic equilibrium maintained betwen two pools

Question 14

Shift to a left

Answer 14

• The further to the right you go… the more mature you get
• Shift to the left means that you have MORE IMMATURE cells (band cells)
  
  • seeing less mature neutrophils in the blood; signifiying the bone marrow can’t keep up with an infection or something
• Increase % of band forms in the blood termed “Shift to the left”

Question 15

Monocytes - macrophages

Answer 15

• Macrophages develoop from monocytes and are distributed throughout the body with name being dependent upon location of the cells
  
  • kupffer cells in liver, osteoclasts in bone etc
• Monocytes circulate for approximately 8 hours, then enter the tissues to differentiate into macrophages

Development stages: stem cell –> monoblast –> promonocyte –> monocyte –> macrophage

Question 16

lymphopoiesis

Answer 16

• production of cells in lymphocytic lineage, including T lymphocytes, B lymphocytes or natural killer cells (NK cells)
  
  • B lymphocytes and NK cells –> develop ENTIRELY in the bone marrow and released into the peripehral blood
  • T lymphocyte maturation sequence
    
    • In bone marrow untell prothymocytes are released into peripheral blood to migrate to the thymus
    • once in thymus, termed thymocytes
    • within thymus –> mature/differentiate into T lymphocyte subsets
    • Most thymocytes DIE in the thymus (positive and negative selection

Question 17

Thrombopoiesis

Answer 17

• Define: production of platelets (aka thombocytes)
  
  • anuclear cytoplasmic remnants of megakaryocytes
  • Role in hemostasis –> limit bleeding, repair endothelium
• Megakaryocytes undergo endomitosis (nuclear mitosis without cytoplasmic division) –> large polyploid (32N) cell
• THROMBOPOIESIS STIMULATED BY THROMBOPOIETIN
  
  • promotes megakaryocyte precursor production
  • stimulates endomitosis

Question 18

formation of platelets

Answer 18

• project these long cytoplasmic extension which constrict at various points and divide into fragments –> forms platelets
• platelet is phagocytized in liver or spleen
• emergency reserve of platelets in the spleen

Question 19

absolute cell count vs differential count

Answer 19

• absolute cell count = provides quantitiy of each cell type per unit of volume
• Differential count = relative count; gives the % of each cell type

LOOK AT BOTH VALUES