Haemopoiesis Flashcards
Where does haemopoiesis occur in adult life?
In the bone marrow, the soft tissue within the centre of bones where blood cells develop
In certain pathological conditions Haemopoiesis may also develop in other tissue including liver, lymph nodes and spleen
In the foetus where does haemopoiesis occur?
In the bone marrow and in the liver, spleen and lymph nodes during foetal development
Where does Haemopoiesis occur in the embryo?
In the yolk sac
What is it called when haemopoiesis is taking plac within vs outside the bone marrow?
Intramedullary - H occuring within the bone marrow
Extramedullary - H occuring outside the bone marrow (spleen and liver)
Where is the initial site of formation of blood cells and developmental circulatory system?
The yolk sac that is part of the embryonic tissue
-Specialised zone called Area Vasculosa develops in part of the yolk sac and this is where the blood vessels are found
When does the blood formation period known as the mesoblastic phase or embryonic phase commence?
As early as week 2 to 3 of gestation
What are the 3 phases in Haemopoiesis?
- The Mesoblastic or Embryonic phase
- The Hepatosplenic phase
- The Myeloid or Bone Marrow phase
What happens in the mesoblastic or embryonic phase?
-In the first few weeks of gestation and up until abt 2 months the yolk sac is the area of Haemopoiesis
-Areas known as blood islands form in the area vasculosa by migration of cells from mesoderm of the yolk sac
-The first precursor blood cells are found in the dorsal aorta region
-Primitive blood vessels are formed and the cells lining these vessels secrete primitive plasma
-Primitive Haemopoiesis at this stage is primarily erythropoieitic and blood cells are produced
-Primitive Haemoglobin (Gower and Portland) also begin to form
What are Primitive Haemoglobin?
Gower and Portland
What is the Hepatosplenic phase and when does this occur?
-The hepatosplenic phase primarily involves the liver and is maximal at 4 months (2-7 months declining towards birth)
-To a lesser extent, cell production also occurs in the spleen
What happens in the Hepatosplenic phase i.e what is formed?
-In the foetus the major organs are being formed and developed : in relation to haemopoeisis the liver, spleen and thymus are capable of producing blood cells
-Haemoglobin F (foetal Hb) is produced in the red cells
-Because there is rapid development, the need for blood increases
When does Myeloid (Bone Marrow) Phase occur?
-Between months 5-9 in the foetus and continues throughout life
What happens in Myeloid (Bone Marrow) Phase?
-Halfway into foetal life, the bone marrow takes over from the liver and spleen and beings to produce HbA
-The bone marrow is the production site for blood cells for the rest of life
What happens if the bone marrow collapses or is in a diseased state?
Haemopoiesis can revert to the liver and spleen can resume Haemopoiesis (extramedullary haemopoiesis)
What is the main Hb in adults?
HbA (Hba with a little Hb A2 and HbF)
What are the sites of haemopoiesis in the foetus?
0-2 months - yolk sac
2-7 months - liver, spleen
5-9 months - bone marrow
What are the sites of haemopoiesis in infants vs adults?
Infants - bone marrow (practically all bones)
Adults - vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal ends of femur
Where shoulf immature cells be found?
Only in the soft tissue in the bone marrow
What is the major haemopoietic organ in adult life?
Bone marrow - red marrow is where haemopoiesis takes place
-Yellow marrow is essentially a fat store - 1:1 ratio of fat cells to haemopoeitic cells in normal healthy 20 year old
What happens bone marrow as you age?
Gradual replacement of the active red marrow with fatty (yellow) marrow
-Cellarity decreases as people age - cells replaced by fat cells
How many blood cells does the bone marrow produce each day?
5 - 10 x 10*11
What does Haemopoiesis rely upon?
-Growth factors
-Cytokines
-Environmental factors
-Amount of oxygen in the body
How long do granulocytes vs erythrocytes last in the bloodstream?
Granulocytes - hours
Erythrocytes - weeks -months 120 days
What does an increased blood cell production mean?
-Occurs when an increased number of cells is required in response to increased demands e.g blood loss and infection
What are all precursor cells derived from?
Haemopoietic Pluripotent stem cell
What are the 2 characteristic features of stem cells?
-Ability to proliferate to produce more cells and ability for self renewa
-Has potential to undergo proliferation and develop into separate lineages (differentiation) and eventually produce highly specialisedcells which through a process of maturation will develop into mature blood cells
What are the 5 stages in Haemopoeitic Cell Development?
- Stem cell - capacity for self renewal and proliferation
- Differentiation and lineage selection (specialisation)
- Maturation - non-dividing cells will develop into mature cells
- Functional mature cells
- Cell death - apoptosis
What does the pluripotential stem cell produce?
Progenitor cells
-the progenitor cells can be multipotent (mixed) or unipotent
What are Multipotent Colony Forming Cells?
(CFU-GEMM)
-These progenitor cells can proliferate and differentiate into mature cells of m´various myeloid lineages
What are Uni potent progenitor cells?
(CFU-E)
-These can produce cells that mature into erythrocytes
What does a Bone Marrow Trephine Biopsy show?
Takes a snapshot of what bone marrow actually looks like
Tree diagram slide 20
What are the most important cells in the haemopoetic system?
-Stem cells
-Responsible for regenerating haemopoiesis following bone marro/ stem cell transplantation or severe cytotoxic damage to haemopoietic system e.g after chemo or radiotherapy
Are stem cells found in normal peripheral blood?
Stenm cells and immature progenitor are found in very low numbers, lower than in the marrow - can be increased w drug trewatment
What is a rich source of stem and progenitor cells?
Umbilical cord blood
What doe stem cells have to possess?
Generally agreed that stem cells are found among cells that possess the CD34 cell markers - must test for antigen before transplant
What are haemopoietic growth factors?
-glycoproteins hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and the function of mature red cells
-regulate the balance between haemopoiesis and apoptosis
-the growth factors react to external stresses such as infection or blood loss
How do growth factors work?
-They are produced in different organs in the body
-They bind to surface receptors on target cells (cfus) and can trigger replication, differentiation and functional activation of their target
What are examples of Haemopoietic Growth Factors or Coloy Stimulating Factors?
-EPO - erythropoietin - production of RBCs
-G (Granulocytes ) CSF
-M (Macrophage) CSF
-GM-CSF - granulocytes and macrophages
-IL (Interleukin) 3
-Thrombopoietin - regulates iron in blood system
-Stem Cell Factor
-VE (vascular endothelial growth factor)
What makes haemopoietic growth factors and other regulatory cytokines different to classical hormones?
-Haemopoeitic growth factors are produced by several cell types
EPO - where is it produced, what does it target and what cells are produced?
Production - kidney
Target - CFU-E
Cells produced - red cells
GM-CSF - sites of production, target, cells produced?
Production : fibroblast, macrophage, bone marrow, sromal cells, endothelial cells
Target : CFU-GM
Cells produced : Granulocyte, macrophages, monocytes
G-CSF : Sites of production, target, cells produced
Sites of production - Fibroblast, macrophages, bone marrow, sromal cells, endothelial cells
Target - CFU-GM
Cells produced - Granulocytes (neutrophils)
Thromopoietin - sites of production, target, cells produced?
Production- liver cells
Target - CFU-Meg
Cells produced : Megakaryocytes, platelets
Thrombocytopenia?
Low platelets - could be liver disease as dont produce growth factor for platelets
What is the period between the formation of a cell and the completion of mitosis in the newly formed cells known as?
Interphase
What are the stages of interphase?
G0 - cells rest and are not involved in proliferation
G1 - the cell begins to commit to replication
S - DNA content doubles
G2 - cell organelles are copied and cytoplasmic volume increases
(dysregulation of cell proliferation is also the key to the development of malignant disease)
What are adjustments thta can be made to the rates of cell proliferation?
-Cells in G0 may be stimulated to commence DNA synthesis
-The period in G1 may be shortened or prolonged (as may S or G2) and duration of mitosis may vary
What are clinical application of stem cells?
Stem cells can be harvested from blooD and are transplanted to treat patients with Haematological malignancies
