Haematopoeisis Flashcards
What is haematopoiesis
The production of blood cells throughout life
How long do neutrophils last
1 day
How long do platelets last
7-10 days
How long do rbcs live
120 days
How long do lymphocytes and monocytes live
Months or years
All blood cells arise from what type of cell
Haematopoietic Stem Cells
What is a stem cell
A cell that has the ability to continuously divide and differentiate into various other kinds of cells/tissues
Who demonstrated the existence of stem cells
Dr James Till
Dr Ernest McCulloch
Where do stem cells come from
In research they come from IVF embryos that have been donated
Stem cells are taken from these blastocysts
Inner cell mast of blastocyst is taken
What are the sites of haematopoiesis
Bone marrow
Yolk sac
Liver
Spleen
Bone marrow
How many days does it take for an egg to become a blastocyst
6 days
List the sites of haematopoiesis, from most cells produced to least from month one of development into adulthood
Yolk sac
Liver + spleen
Liver
Bone marrow
Comment on the bone marrow during childhood
Childhood marrow volume increases as child grows
Average 3 year old has 1500 ml active marrow
As child grows fat cells accumulate in marrow to form yellow marrow
Adults have approx 30% active (red) marrow
What happens to haematopoeisis if blood cell levels are low
Bone marrow can increase from 30% active to 100% active
Extramedullary haematopoeisis in liver and spleen may also re-occur (in disease)
What does totipotent mean
Can develop into any cell type
What does pluripotent mean
Can develop into some cell types
List some characteristics of stem cells
(6)
Unspecialised
Capable of dividing and renewing themselves for long periods of time
Can differentiate into specialised cell types
Many different functions
Function altered in disease states
Mature cells have short half life
How many Haematopoietic stem cells do we have
Limited number
1 per 20 million nucleated cells
How many cells can a HSC make after 20 divisions
1 million cells
What CD molecule do HSCs express
CD34
What are the two pathways of haematopoiesis
Common myeloid pathway
Common lymphoid pathway
What two cells can the HSC differentiate into
Common lymphoid precursor
Common myeloid progenitor
What cell types result from the myeloid pathway
(7)
Thrombocyte
Erythrocyte
Mast cell
Basophil
Neutrophil
Eosinophil
Macrophage
What cell types result from the lymphoid pathway
(3)
Natural killer cell
T lymphocyte
B lymphocyte (-> plasma cell)
What is the common myeloid progenitor often called
CFU-GEMM
What does CFU-GEMM stand for
Colony forming unit
Granulocytes, erythrocytes, monocyte, megakaryocyte
What is the common lymphoid precursor often called
CFU-L
Colony forming unit - Lymphocytes
How does a stem cell know what it is going to become
It depends what acts on it e.g. hormones such as erythropoietin stimulating the formation of rbc
What is SCF
Stem cell factor
What does stem cell factor do
Stimulates the self renewal of pluripotent stem cells -> makes more
Acts on unipotent stem cells to make rbcs, platelets or wbcs
What is needed for stimulation of erythropoiesis
Granulocyte-macrophage colony stimulating factor
EPO
What is needed for stimulation of thrombopoiesis
Granulocyte-macrophage colony stimulating factor
Thrombopoietin
What is needed for the stimulation of wbcs
Granulocyte-macrophage colony stimulating factor
Lymphocytes -> need no more stimulation
Monocytes need macrocytic colony stimulating factor
Granulocytes need granulocyte colony stimulating factor
How can growth factors for certain cell types be important in donations
These factors can be given to mobilise certain cell types out into peripheral blood so they can be donated easily
What stages of erythropoietin happen in blood
Last two stages -> in rare occasions steps before are seen especially in blood loss
Why does high reticulocytes mean
Loosing blood somehow
What does the presence of nucleated rbcs mean in peripheral blood
Bone marrow is under a lot of pressure to recover rbc count
List the steps involved in erythropoiesis
(6)
Pronormoblast
Early normoblasts
Intermediate (polychromatic) normoblasts
Late (pyknotic) normoblasts
Reticulocytes
Red cells
List the cells in simplified erythropoiesis
(5)
Megakaryocyte-erythrocyte progenitor
Pro-erythroblast
Erythroblast
Reticulocyte
Erythrocyte
List the cells in thrombopoiesis
Megakaryocyte-Erythrocyte Progenitor
Megakaryocyte broken into platelets after TPO stimulation
What happens when granulocyte-monocyte progenitor is stimulated by G-CSF
Neutrophil is formed
What happens when granulocyte-monocyte progenitor is stimulated by stem cell factor
Basophil is formed -> can be converted to a mast cell in tissues
What happens when granulocyte-monocyte progenitor is stimulated by IL-5
Eosinophil is formed
What happens when granulocyte-monocyte progenitor is stimulated by M-CSF
Monocyte is formed
Converted into macrophage in tissues
What does Growth factor (G-CSF) do
Matures cells e.g. neutrophils
Helps cells differentiate
Stops cell becoming other cell types
Suppresses apoptosis
Activates cells e.g. phagocytes
Helps cells proliferate
List the cells in the development pathway of a granulocyte
(9)
HSC (Haemopoietic stem cells)
CFU-GEMM (common myeloid progenitor)
CFU- GM (granulocyte + monocyte precursor)
CFU-Neut
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Mature neutrophil
What five stages come after GM-CFU in the development of a neutrophil
CFU-Neut
Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Mature neutrophil
What are we looking for in bone marrow samples
Myeloid : Erythroid ratio
Done by counting 200 to 300 cells
Why do you need to know the age of the patient before assessing cellularity of bone marrow
Young child has 80% of the intertrabecular space occupied by haematopoietic cells
75 year old has only about 30%
What does a really dark stain of bone marrow mean?
Leukaemia usually -> very little fat presence -> hypercellular
What does a light stain of bone marrow mean
Aplastic anaemia -> hypocellular -> haematopoietic cells replaced by fat cells
What stain do we use on bone marrow
Wrights Stain
What stain do we use on bone marrow to test for iron
Perls Prussian Blue
What happens to iron in bone marrow
10 to 20% of absorbed iron goes into a storage pool in cells of the mononuclear phagocyte system particularly fixed macrophages
Its also recycled into erythropoiesis so theres a balance of storage and use
