Lecture 1: Blood and Bone Marrow Flashcards
What does “Pancytopenia” mean?
Deficiency of all three cellular components of the blood (red cells, white cells, and platelets).
What is the word for “deficiency of all three cellular components of the blood (red cells, white cells, and platelets).”
Pancytopenia
What is Haematopoiesis?
Haematopoiesis is process by which mature blood cells are generated (produced and mature) from stem cells in the bone marrow.
- Because mature blood cells of most types are relatively short-lived (unlike stem cells), haematopoiesis is required constantly even in unstressed adult life to maintain adequate numbers of blood cells.
- During stress, such as with blood loss or infection, additional cell growth is required.
The process of haematopoiesis needs to be regulated with precision since circulating levels of mature cells are maintained within narrow limits of variation, yet cell production can be altered rapidly (huge redundancy) in response to increased or decreased demands.
Why do we need to study haematopoesis?
Why do we need to study haematopoiesis?
- 1) Blood tests i_mportant part of management of patients_ (diagnosis and monitoring)
- 2) Understanding function of blood cells
- Assists in interpretation of investigations
- Important for diagnosis and management of blood disorders, e.g. anaemia, leukaemia (high level of white blood cells)
What are haematopoietic tissues?
In adults, tissues generating non-lymphoid cells of peripheral blood are called haematopoietic tissues and are restricted to:
- Bone marrow (95%): mainly sternum, ribs, sacrum, vertebrae long bones
- Spleen which plays a minor role (5%).
Note that megakaryocyte sheds off platelets, and it only presents in bone marrow.
Note that megakaryocyte ____________, and it only presents in ___________
Note that megakaryocyte sheds off platelets, and it only presents in bone marrow.
Describe the changes of origin of haematopoietic tissue across embryonic development
1) Cells of haematopoietic tissue are generated from mesoderm in blood islands of yolk sac (to produce transient ‘primitive’ blood cells),
2) and then they become ‘definitive’ cells from endothelium in aorta-gonad-mesonephros (AGM) region.
3) The site of haematopoiesis then shifts to fetal liver (+ spleen) and subsequently bone marrow.
What is the origin of haematopoiesis after birth? (infancy-> adult)
- In infancy, all bone marrow is haematopoietic.
- During childhood, there is progressive fatty replacement of marrow throughout l_ong bones_.
- In adult life, haematopoietic marrow is confined to central skeleton (axial skeleton). In adult haematopoietic areas, ~50% marrow consists of fat.
- Fatty marrow is capable of reversion to haematopoiesis.
- In some blood disorders, there is expansion of haematopoiesis into long bones.
- Spleen and liver can also resume their fetal haematopoietic roles, so-called ‘extramedullary haematopoiesis’.
- In myelofibrosis of splenomegaly, there is fibrosis and extramedullary haematopoiesis.
- Fatty marrow is capable of reversion to haematopoiesis.
- Clinical: So if an adult-patient needs a bone biopsy, we need to biopsy a site that has active haematopoesis
*
What is Myelofibrosis
Scarring of the marrow
What are the 2 abnormalities of haematopoiesis sites?
Fatty marrow is capable of r_eversion to haematopoiesis._
- In some blood disorders, there is expansion of haematopoiesis into long bones.
Spleen and liver can also resume their fetal haematopoietic roles, so-called ‘extramedullary haematopoiesis’.
- In myelofibrosis of splenomegaly, there is fibrosis and extramedullary haematopoiesis.
- Myeloflibrosis = fibrosis of the marrow
- Normal bone for haematopoiesis gets squeezed out and the patients develop enlargement of the liver and the spleen.
- The spleen would have extramedullary haematopoesis
- Normal bone for haematopoiesis gets squeezed out and the patients develop enlargement of the liver and the spleen.
- Myeloflibrosis = fibrosis of the marrow
- Similar things happen for children with severe thalassaemia
Label
1) Fat cells
2) Trabeculae
3) Haematopoietic cells
Describe the Bone Marrow appearances under the microscope
Bone marrow includes
- Trabecular bone
- Fat cells
- Haematopoietic tissue in variable quantities
Cellularity varies from 30-70% and decreases with age
- mild hypocellular = less haematopoetic cells
Major cellular elements are the haematopoietic cells and bone marrow stromal cells.
Describe Haematopoietic Stem Cells
Haematopoieitc stem cells (HSCs) sustain haematopoiesis but constitute a very _small fractio_n (1 in 10,000-100,000) of the total bone marrow blood cell population.
Stem cell properties include:
- 1) Self-renewal
- 2) Generation of one or more specialised cell types
Human HSCs express antigen CD34 and this is used as a measure of stem cell number, particularly when preparing cells for transplantation.
Umbilical cord blood is enriched in HSCs and is therefore used increasingly as a source of stem cells for transplantation, especially in paediatric population. The other more common way in adult population is peripheral blood stem cell collection.
What are the Haematopoietic Stem cell properties?
Stem cell properties include:
- Self-renewal
- Generation of one or more specialised cell types
What are Haematopoietic Stem Cell Niches?
2 Niches in the bone marrow microenvironment that support haematopoietic stem cells
1) Endothelial Niche
2) Endosteal niche
* The hematopoietic stem cell (HSC) niche is the anatomical location in which HSCs reside and self-renew. The HSCs outside the niche do not self-renew and commence the process of differentiation to ultimately produce mature blood cells.*
What is the hierachy of haematopoiesis?
1) Stem cells generate progenitor cells
2) Progenitor cells generate morphologically identifiable progeny that progressively mature (can’t proliferate)
- Lymphoid progenitor
- Myeloid progenitor
3) As cells mature they lose their capcity to proliferate
What kind of mature cells are found in the bone marrow?
The marrow represents a heterogeneous collection of cells without the stratification seen, for example, in the skin or gut.
Despite this, a series of maturing haematopoietic cells can be recognised for each lineage.
- E.g. In neutrophilic granulocyte development, there are a series of distinct cells that differentiate into mature granulocyte.
- Recognisable cells in this lineage (from less to more mature) are termed promyelocytes, myelocytes, metamyelocytes, band neutrophils and segmented neutrophils.
It is only last cell population that is observed in blood. Earlier development of this lineage normally occurs in bone marrow.
In general, only the most mature cells in each lineage enter the circulation in significant numbers, although small numbers of stem cells and progenitors are present in the circulating blood.
Describe the regulation of haematopoiesis
Haematopoiesis, both s_teady-state and emergency_, requires precise regulation.
This regulation is quite complex, with two key elements involved achieving precise control, i.e. 1) transcription factors (Don’t need to know details) and 2) cytokines. ( e.g. gorwth factors- need to know some detail)
The main regulator are the growth factors that control the production of haematopoetic cells. (purple= growth factors that are produced in the micro environemnt that regulate the development and maturation of the blod cells)
The stem cells and the progenitors have receptors to these growth factors (glycoproteins)
- EPO erythropoietin (stimulate RBC production )
- G-SCF stem cell factor (stimulate neutorphil production)
- TPO thrombopoietin (stimualte platelet production)
- IL interleukin
