What results from the increase in cytoplasmic granulation in megakaryocytes?
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More granulation results in more platelets produced per megakaryocyte.
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What results from the increase in cytoplasmic granulation in megakaryocytes?
More granulation results in more platelets produced per megakaryocyte.
How many neutrophils are produced per day?
2 x 10^10.
What causes Agammaglobulinemia?
A block in B cell development.
What is done in an aspirate assay?
Semi-liquid bone marrow is aspirated and smeared onto a slide for cell count and type analysis using a light microscope and stains.
What are the two types of growth factors in lymphocyte haematopoiesis?
Early acting growth factors and late acting growth factors.
Where do circulating red cells pick up oxygen?
In the alveoli.
Which growth factor is used for platelet production?
TPO (Thrombopoietin).
How does poor kidney function affect the bone marrow's production of red cells?
It reduces the ability to upregulate bone marrow production of red cells.
How do haematopoietic tissues respond to increased cell production needs?
They can respond rapidly, e.g., in cases of blood loss or infection.
Where does haematopoiesis occur in adults?
In the bone marrow of the axial skeleton.
What can monocytes become when they migrate from blood into tissues?
Macrophages.
Which protein is defective in Agammaglobulinemia?
BTK (Bruton's tyrosine kinase).
What do the earliest progenitors of megakaryocytes look like?
The earliest progenitors of megakaryocytes look like myeloid blasts.
What role do oxygen sensors in the kidney play in erythropoiesis?
They act on the peritubular interstitial cells in the outer cortex of the kidney to produce EPO.
What is the primary function of white blood cells (leucocytes)?
Immunity.
What are the types of granulocytes?
Eosinophils, basophils, and neutrophils.
What are the key roles of monocytes?
Phagocytosis and cytokine production.
What are the two main reasons for low cell counts?
Cells are not being produced by the bone marrow (aplastic anaemia) or cells are destroyed too quickly in peripheral circulation (immune thrombocytopenia).
Where do early progenitors of T cells come from?
Bone marrow.
Where are mast cells produced and where do they mature?
Produced in the bone marrow but mature in tissues.
What is the purpose of evaluating haematopoiesis?
To get access to cells of the bone marrow.
What is the consequence of a defect in the BTK protein in Agammaglobulinemia?
Inability to progress from Pre B cell to immature B cell.
What controls erythropoiesis?
The kidney controls erythropoiesis.
Which growth factor is used for red cell production?
EPO (Erythropoietin).
Where does erythropoiesis start?
Erythropoiesis starts in the bone marrow with stem cells.
When does haematopoiesis start and where does it continue throughout life?
Starts 17 days after fertilisation and continues throughout life in our bone marrow.
What do myeloid progenitors differentiate into?
They either go down the granulocytic pathway to GMP cells and then into eosinophils, neutrophils, monocytes, or basophils, or they differentiate into MEP cells which then become erythrocytes, megakaryocytes, or platelets.
What causes acute leukaemia?
Maturation arrest, where a block in haematopoiesis results in lots of blasts but not the later cells in the hierarchy.
What is an example of leukaemia caused by over-production of mature cells?
Chronic myeloid leukaemia (CML).
What part of the immune response are granulocytes involved in?
The innate immune response.
Where do B cells develop?
In the bone marrow.
What is the sequence of B cell development in the bone marrow?
Stem cells differentiate into Pro B, Pre B, Immature B, and then mature B (antigen naïve).
What role do transcription factors play in haematopoiesis?
They control which genes are turned on or off by binding to DNA and promoting or blocking gene transcription.
How many red blood cells are produced per day?
4 x 10^11.
How do high oxygen levels in the blood affect EPO production?
High oxygen levels result in low EPO production and vice versa.
What do Haematopoietic Stem Cells (HSC) commit to becoming?
Multipotent progenitor cells, either myeloid or lymphoid.
What are the two classes of myeloid cells?
Monocytes and granulocytes.
What are the two types of thrombopoietin (TPO) receptor agonists?
AMG 531 (subcutaneous injection) and Eltrombopag (oral).
With what type of disease are basophils associated?
Allergic disease.
From which part of the body is bone marrow usually taken for evaluation?
The iliac crest.
What types of cells are found in the bone marrow of someone with Agammaglobulinemia?
Lots of Stem cells, Pro B, and Pre B cells, but no immature or mature B cells in circulation.
What is the lifespan of red blood cells?
120 days.
What does it mean that haematopoietic stem cells (HSC) are multipotent?
It means they can give rise to multiple types of blood cells.
What is a side effect of liver dysfunction related to platelet production?
A side effect of liver dysfunction is thrombocytopenia (low blood platelet count) due to lack of TPO production.
What happens if red cells are being destroyed in the periphery?
Erythropoiesis will be stimulated, leading to an increase in precursors such as reticulocytes.
What are the two categories of white cells?
Lymphoid cells and myeloid cells.
Where are monocytes made?
In the bone marrow.
What is erythropoietin (EPO) mainly used for?
To improve anaemia in end-stage renal disease.
How long do neutrophils live in the blood before migrating into tissues?
A few hours.
What happens to B cells once they recognize antigens?
They further differentiate in the lymph nodes.
What type of genetic disorder is Agammaglobulinemia?
X-linked genetic disorder.
What is absent in the circulation of someone with Agammaglobulinemia?
Immature or mature B cells and immunoglobulins (Ig).
What is haematopoiesis?
Haematopoiesis is the process of blood cell formation starting with a stem cell.
Where is the TPO receptor (c-Mpl) found?
The TPO receptor (c-Mpl) is found on megakaryoblasts, megakaryocytes, and platelets.
At what stage are cells committed to the erythrocyte lineage?
Cells are committed to the erythrocyte lineage once they reach the Pronomoblast stage.
How many cells arise daily from bone marrow?
10^12 cells.
How are early cells in the haematopoiesis pathways identified?
By functional assay.
What are some other uses of erythropoietin (EPO)?
Myelodysplasia, pre-autologous blood donation, Jehovah’s witness blood loss, and sporting abuse.
What happens when there are low levels of platelets?
It leads to easy bruising and hemorrhage.
What is a trephine biopsy and what is it used for?
A core of bone marrow is taken to examine cellularity, histology, and architecture of the bone marrow.
What is the role of early acting growth factors in haematopoiesis?
They act early on in the hierarchy of haematopoiesis.
What are the capabilities of haematopoietic stem cells (HSC)?
HSCs can divide indefinitely to replenish themselves and give rise to specialized, differentiated cells.
Where is thrombopoietin (TPO) mainly produced?
TPO is mainly produced by the liver.
What happens to the nucleus in cells further down the erythrocyte lineage?
The nucleus gets much smaller until it is extruded in reticulocytes.
Why can reticulocytes make hemoglobin (Hb) but erythrocytes cannot?
Reticulocytes still have RNA, which allows them to make hemoglobin.
Where does haematopoiesis occur in a foetus?
Initially in the yolk sac, then moving to the foetal liver.
How are later cells in the haematopoiesis pathways identified?
Via routine marrow staining.
What are the two types of haematopoietic stem cell transplants?
Autologous (from the individual) and allogeneic (from a donor).
What conditions are TPO receptor agonists used for?
Thrombocytopenia in myelodysplasia and post-chemotherapy to maintain/increase platelet count.
What part of the immune response are lymphocytes involved in?
The adaptive immune response.
What is the role of dendritic cells in the immune response?
To detect antigens in the tissue and present them to the innate and adaptive immune system.
What additional analysis can be performed on cells obtained from an aspirate assay?
Chromosome analysis.
How many platelets are produced per megakaryocyte?
Around 2000 - 3000 platelets are produced per megakaryocyte.
Which growth factors are important for neutrophil production?
G-CSF and GM-CSF.
What is erythropoiesis?
Erythropoiesis is the haematopoietic pathway for erythrocytes (red blood cells).
What is the lifespan of lymphocytes?
Days to years, possibly for life.
What is haematopoiesis?
The process of blood cell production.
What is the primary function of platelets?
Clotting.
How long does an erythrocyte transfusion last?
1 month.
What is G-CSF used for?
Prevention of infections in neutropenic patients and mobilizing stem cells for harvests prior to transplants.
What are dendritic cells and where are they found?
Professional antigen-presenting cells found in tissues.
How is a bone marrow biopsy typically performed?
Via a needle.
What are the two types of assays used to evaluate bone marrow?
Aspirate and Trephine Biopsy.
What does a hypocellular bone marrow indicate?
Low cell bone marrow, e.g., aplastic anaemia.
What does a normal bone marrow look like in a trephine biopsy?
It has lots of little cells.
From which cells do platelets arise?
Platelets arise from the cytoplasm of megakaryocytes in the bone marrow.
Can you name some examples of early acting growth factors?
Stem cell factor, Flt 3 ligand, IL-3, TPO.
Why do megakaryocytes enlarge?
Megakaryocytes enlarge due to nuclear divisions (endomitosis).
What is the role of late acting growth factors in haematopoiesis?
They act late in the hierarchy of haematopoiesis.
What regulates platelet production?
Platelet production is regulated by thrombopoietin (TPO).
What is the lifespan of neutrophils?
<48 hours.
What does EPO stimulate in the bone marrow?
EPO stimulates the later stages of erythropoiesis in the bone marrow.
What is the lifespan of platelets?
8-12 days.
What might poor kidney function mean for EPO production?
Poor kidney function may mean an individual cannot produce EPO.
How many platelets are produced per day?
1 x 10^12.
Why is EPO usually given in cases of renal failure?
Because individuals with renal failure may not be able to produce EPO.
What do reticulocytes differentiate into?
Reticulocytes differentiate into red blood cells, which then pass into circulation.
What regulates haematopoiesis?
Growth factors and cytokines.
What are the three types of blood cells?
Red cells (erythrocytes), platelets, and white cells (leucocytes).
Where does haematopoiesis occur in infants?
In the bone marrow of virtually all bones.
What do lymphoid progenitors differentiate into?
T lymphocytes, B lymphocytes, or NK cells.
What are the three methods to increase cell counts when they are low?
Replace them, use growth factors, and use thrombopoietin receptor agonists.
How long does a platelet transfusion last?
A few days.
What is an example of acute leukaemia caused by maturation arrest?
Acute myeloblastic leukaemia (AML).
What is the purpose of haematopoietic stem cell transplants?
To repopulate the bone marrow in patients with immune deficiency or blood cancer.
What do monocytes engulf and destroy?
Dead host cells and pathogens.
What is the consequence of no negative feedback on haematopoiesis in the system?
It can lead to over-production of mature cells and potentially leukaemia.
What is the primary function of neutrophils?
To engulf and destroy bacteria (phagocytes).
What do the granules of neutrophils contain?
Lysosomes and myeloperoxidase.
Where do T cells differentiate and get selected?
In the thymus.
Where do NK cells develop?
In the bone marrow.
What is used in patients with low platelets to stimulate platelet production?
Thrombopoietic growth factors (GF) are used in patients with low platelets to stimulate platelet production.
What is the primary function of red blood cells (erythrocytes)?
Oxygen transport.
What are the three types of lymphoid cells?
T cells, B cells, and NK cells.
What happens when there is no maturation arrest in haematopoiesis?
It leads to over-production of mature cells, which can also lead to leukaemia.
What cytokines do monocytes produce that are important for intracellular immunity?
IL-12 and IFN gamma.
Are eosinophils phagocytic?
No, they are not phagocytic.
What is the lifespan of platelets?
8-12 days.
What are the risks associated with regular blood transfusions?
Patients can be given too much iron, leading to iron overload, which is toxic to the liver.
What type of infections are eosinophils used in response to?
Parasite infections.
What is the function of the granules in platelets?
To secrete substances that control clotting and the breakdown of a blood clot.
Do platelets have a nucleus?
No, platelets have no nucleus.
