Haematopoeisis Flashcards
What is haematopoeisis?
The generation of blood cells in the BM.
Why does haematopoeisis need to be continuous throughout life?
For continuous replenishment to maintain the concentrations and for increased production during stress e.g. infection or blood loss
What are the two lineages of blood cells that can arise from a haematopoeitic SC/progenitor?
Myeloid and Lymphoid
What cells develop from the lymphoid lineage?
T lymphocyte
B lymphocyte
NK cell
Which two types of progenitors arise from the myeloid lineage?
Granulocyte macrophage progenitor (gmp)
Megakaryoctye erythroid progenitor (mep)
What cells arise from an MEP?
Erythrocyte / RBC
Megakaryocyte —> Platelet
What cells arise from GMP?
Eosinophil
Neutrophil
Basophil
Monocyte —> Macrophage
Describe the function and structure of an erythrocyte.
Carry O2 and CO2.
Biconcave with no nucleus for maxiumum transport efficiency
How many erythrocytes are in the body and how long do the survive?
120 days. Only 1 month with transfusions
5x10^12.L
Describe the function of a platelet.
Secrete substances to control the formation and breakdown of clots by forming part of the clot itself.
How long do platelets survive and how are they removed?
7-10 days
Removed by macrophages in the liver and spleen
150-450x10^9/L
What is a Leucocyte / WBC?
A group of cells that arises from a haematopoeitic SC whose function is within the immune system. Refers to lymphocyte, neutrophil, eosinophil, basophil and monocyte.
How long do lymphocytes survive?
Days to years depending on immune memory
What is the function of a T lymphocyte?
Formed in the BM but matures in the thymus. Kills infected cells (CD8) and produces cytokines to activate B cells and macrophages (CD4).
What is the function of a B lymphocyte?
Made in the BM. They are plasma cells that produce antibodies and memory cells.
What is the function of a NK cell?
Kills foreign cells directly of via antibodies
What is the function of a monocyte and how long do they survive?
Monocytes circulate in the blood and enter tissue to become macrophages. They kill infected cells via phagocytosis and present antigens to lymphcytes for an adpated immune response.
Last days to weeks
Which cells form this group of WBCs?
Neutrophils, eosinophils and basophils
What is a neutrophil?
Live in the blood but migrate to tissue for 4-5 days. Phagocytic actions to bacteria and dead cells. Contain lysosymes and myeloperoxidase.
What must a pt with neutrophil deficiency be treated with?
Prophylactic antibiotics - medical emergency
What is the function of eosinophils and basophils?
Basophils release histamine and heparin in allergy response.
Eosinophils are involved in allergy and parasite immunity.
What are dendritic cells?
Antigen presenting cells for T lymphocytes.
Where are mast cells matured and what do they do?
Produced in BM but mature in tissues. Release histamine and heparin for allergy responses. Similar to basophils but they do not circulate in the blood.
When does haematopoeisis begin?
At day 17 of gestation.
Where does haematopoesis take place and how does this change with development?
Begins in the fetal yolk sac —> AGM (aorta-gonad-mesonephros region) —> Liver and spleen —> Bone marrow at 6 months old
Where is BM extracted from in adults?
Axial skeleton
How can BM be tested?
Functional assay - SC and progenitors
Marrow staining - Precursor and mature cells
Immunophenotyping - specific proteins and cell markers
What marker shows that the BM is recovering from damage?
CD34 levels rise on HSC.
What can be used to mobilise BM for harvesting?
G-CSF
What is red marrow?
Marrow where there is active haematopoiesis and has a rich blood supply, forms 30-70% from the cells
What is yellow marrow?
Purely fat cells where no haematopoiesis occurs.
If BM capacity is compromised or exceeded, where else can haematopoiesis occur?
Liver and spleen in extracellular haematopoiesis.
In what conditions may the BM be compromised?
Myelofibrosis and thalassaemia
What is required for a HSC to differentiate into progenitor cells?
Intrinsic factors - Lineage determining TF
Extrinisic factors - soluble GF
The factors form a marrow microenvironment / stroma
What is the function of a reticular fibrocyte?
Line the surfaces of sinuses and have extended cytoplasmic processes to create a lattice in which blood cells are found.
Where are BM samples taken from?
Posterior Iliac crest
What will a BM sample show?
Trephine is the core of the BM that shows cellularity, structure and ECM. An aspirate will show the number of cells in each stage and abnormal infiltrates.
What is a blast cell?
A cell that is transitioning from HSC to multipotent progenitor cells.
What regulates the growth of a platelet from a megakaryoblast?
TPO produced by the liver
How many platelets arise from one megakaryocyte?
2000-3000
What regulates the growth of a granulocytes from promyelocytes?
G-CSF (colony stimulating factor)
What regulates the growth of monocytes from promononcytes?
GM-CSF
When do granulocytes gain their enzymes and granuoles?
As the mature
Why do granulocytes not have the ability to proliferate?
Lose chromatin as they mature
What regulates the process of erythropoiesis?
EPO produced by the kidney and partially by the liver when there is a need for increased O2 carrying capacity.
What stimulates the production of EPO and why might this occur?
Hypoxia increases mRNA transcription. Hypoxia may be caused by bleeding or haemolysis
What are the stages of development of a RBC?
Pronormoblast/Proerythroblast —> Normoblast —> Reticulocyte —> Erythrocyte
What changes occur in a RBC as it matures?
The nucleus condenses and Hb concentration increases changing the colour to pink.
Loss of the nucleus forms a reticulocyte, which now only contains ribosomal RNA to synthesis Hb.
Reticulocytes stay in BM for 1-2days before moving to blood to mature.
What does an increase in reticulocytes in the blood indicate? When may this occur?
Shows an increase in erythropoiesis due to stress of more RBCs being required. Haemolytic anaemia
What does the production of erythrocytes require?
Iron, B12, Folate
Vit B6, Vit C and E, Cobalt, AA, manganese
What is administered to correct cell line failures? Give examples.
Haematopoietic GFs. EPO for anaemia TPO for thrombocytopenia G-CSF for neutropenia IL-7 in HIV for the lymphocytes
How does low blood cell production present in BM samples?
Trephine is hypocellular with mainly fat cells
Aspirate present with blasts which are unable to mature
What can EPO be used to treat?
Improve anaemia and reduce need for transfusion.
Treat endstage RF.
Myelodysplasia, Pre-autologous blood donation, Jehovah’s witnesses blood loss.
Treat anaemia in pts receiving chemo or radiotherapy.
Given subcut
What needs to be administered along side EPO?
Iron and folate supplements
What are the S.E. of giving EPO?
Hypertension and thrombosis due to increased haematocrit and viscosity.
Which condition causes a reduction in erythrocyte production?
Hypothyroidism
Why is G-CSF given?
To treat neutropenic patients to prevent infections by stimulating SC mobilisation. Can be used to mobilise SC for harvesting
Given subcut
When is TPO given?
TPO receptor agonist given subcut as Romiplastin or orally as eltrombopag for immune thrombocytopenia in myelodysplasia and chemotherapy.
What is the definition of leukaemia?
Cancer of haematopoeitic cells arising in BM and spreading to blood, lymph and spleen
What is the definition of lymphoma?
Cancer of the cells in the lymph and spleen that spreads to the BM and blood
What is a myeloma?
Cancer of the plasma cells in BM
Which two conditions are preleukaemic?
Myeloproliferative disease
Myelodysplasia
= Abnormal myeloid proliferation
What is the cause of acute leukaemia?
Maturation arrest
What is the cause of chronic leukaemia?
Over production of mature cells and no arrest
How are cancers of the BM classified?
Based on their lineage.
Acute myeloblastic Leukaemia (No maturation = progenitor) or Chronic myeloid leukaemia
Acute lymphoblastic leukaemia (No maturation = progenitor) or Chronic lymphocytic leukaemia
