Haemopoiesis Flashcards
What is haemopoiesis?
Formation of BLOOD cells
What is the name for mature red cells?
Erythrocytes
Do mature red cells (erythrocytes) have a nucleus?
NO
What is the function of erythrocytes?
O2/CO2 transport
Do platelets have a nucleus?
NO
What is the role of platelets?
They are involved in primary haemostasis
Formation of the platelet plug
Name the 3 groups of white cells.
- Granulocytes
- Monocytes - macrophages
- Lymphocytes
Name the 3 granulocytes.
- Neutrophils
- Eosinophils
- Basophils
What do neutrophils have a role in?
Phagocytosis and acute inflammation
What do eosinophils do?
- Destroy parasites.
* Modulate hypersensitivity reactions.
What do basophils do?
Modulate hypersensitivity reactions
What is the main type of monocyte?
Macrophage
What do macrophages do?
Modulate immune reactions, involved in phagocytic clearance, regulatory functions
Name the 3 types of lymphocyte.
- B cells
- T cells
- NK cells
What are the 3 types of lymphocyte? And what are they involved in?
B cells – humoral immunity (antibodies). T cells – cell-mediated immunity, regulatory functions. Natural killer (NK) cells – anti-viral/tumour.
What is erythropoiesis?
Production of red cells
What is thrombopoiesis?
Production of platelets
What is myelopoiesis/granulopoiesis?
Production of bone marrow and all the cells that arise with it
What is lymphopoeisis?
Production of lymphocytes
In a steady state ….
Cell loss is balanced by cell production
What is the lifespan of red cells?
120 days
What is the lifespan of neutrophils?
7-8 hours
What is the life span of platelets?
7-10 days
How many red cells are lost and produced per minute?
~2.5million
How many neutrophils are lost and produced per minute?
~1-2million
How many platelets are lost and produced per minute?
~1million
What do mature cells come from?
Precursor cells
What cell is formed just before the reticulocyte? What is the difference between these?
The late normoblast – contains a nucleus which is lost to form the reticulocyte
The late normoblast has a nucleus but when it becomes a reticulocyte it loses the nucleus but keeps some RNA
T
‘Cytoplasmic fragments of megakaryocytes’ refers to what cell type?
Platelets
Describe a megakaryocytic.
Has a polypoid nucleus, nucleus can divide many times without the cytoplasm having to also divide
What does the term ‘blast’ mean?
A NUCLEATED precursor cell
What are megakaryocytes?
Platelet precursor cells
What are the characteristic features of megakaryocytes/
They are polypoid
What is a reticulocyte?
An immediate red cell precursors
What is the characteristic appearance of reticulocytes?
‘Polychromasia’
What are myelocytes?
Nucleated precursors, arising between neutrophils and blasts
Where do all precursor cels come from?
The haemopoietic progenitor cell.
Where do progenitors and ultimately all haemopoietic cells come from?
Haemopoietic stem cells
What cells can self-renew?
HSC - stem cells
What happens as a haematopoietic stem cell as it divides?
It divides asymmetrically, producing 2 cells – one which has the exact same properties as the parent cell (self-renewal).
What happens to self-renewal as you go down the haemopoietic tree?
It is lost
What happens in the proliferation stage?
There is an increase of cell numbers
What happens with regard to differentiation in haemopoiesis?
Descendents commit to one or more lineages
What happens when descendents reach maturation?
They acquire self-renewal: a property of stem cells, lost in descendents
What happens in apoptosis?
Descendents undergo cell death
Outline the main developmental events in haemopoiesis.
- Proliferation: increase in numbers
- Differentiation: descendents commit to one or more lineages
- Maturation: descendents acquire functional properties and may stop proliferating
- Apoptosis: descendents undergo cell death
Stem cell/progenitor/precursor cell concepts and terminology NOT rigid
T
Overlap between developmental events (e.g proliferation and maturation can occur simultaneously)
T
What are more primitive progenitors (e.g stem cells) like during steady-state haemopoiesis?
They are quiescent/dormant
What cells are dormant during steady-state haemopoiesis?
HSC
What 3 things can the term ‘myeloid’ refer to?
- Marrow – e.g. ‘myeloid’ or marrow malignancy.
- Lineage – e.g. non-lymphoid.
- Granulocytes and precursors – myeloid:erythroid.
What are haemopoietic stem cells derived from?
Mesoderm
As early as when are circulating committed progenitors detectable?
Week 5
What is the first site of erythroid activity? When does this stop?
Yolk sac - stops at week 10
In utero, what are the other sites of haemopoiesis (aside from the yolk sac)? When does haemopoiesis start in each of these sites by?
- Liver – starts by week 6.
- Spleen – starts by week 12; probably only a small contribution in humans.
- Bone marrow – starts by week 16.
In adults, where does haemopoiesis usually occur?
Only in the axial skeleton and proximal parts of the long bones (i.e. humerus and femur).
Describe what bone marrow is.
A complex organ, surrounded by a shell of bone with a neurovascular supply
- Outer cortical bone – dense.
- Inner trabecular bone – spongy.
Projections of trabecular bone into the bone marrow increases SA
T
What are the 3 main compartments of bone marrow which can be seen under a microscope?
- Cellular
- CT matrix
- Vascular elements
Name the 2 main cellular components of bone marrow.
- Haemopoietic cells.
* Non-haemopoietic cells e.g. adipocytes, fibroblasts, osteoclasts, osteoblasts.
What does the blood supply to the bone marrow come from?
- Nutrient artery.
+ - Periosteal network.
Instead of arterioles forming capillaries as usual, what happens in bone marrow?
Arterioles drain into ‘sinuses’.
What are sinuses?
Wide venous vessels which open into larger central sinuses
What is the difference between sinuses and capillaries?
Sinuses are larger and have a discontinuous basement membrane (allows blood cells to get out of bone marrow and into blood).
What surrounds sinuses?
Endothelial cells, with gaps between them to allow escape of blood cells
What is the importance of the adventitia cell that lines sinuses?
It has muscle filaments in it, so can contract to regulate the size of the sinus/gaps
How do fully formed blood cells enter the circulation?
By passing through fenestrations in endothelial cells.
What is the release of RED CELLS into the circulation associated with?
Sinusoidal dilatation and increased blood flow.
What do neutrophils do when they require release into the circulation?
They actively migrate towards the sinusoid.
What do megakaryocytes do in relation to sinusoidal blood vessels?
They extend long branching processes called proplatelets into the sinusoidal blood vessels
Red marrow is haemopoietically active
T
Yellow marrow is haempoietically inactive and fatty
T
What is the relationship between yellow marrow and age?
Yellow marrow increases with age
What does the decreased red marrow with increasing age result in?
Reduced marrow cellularity in older individuals
How can marrow cellularity be estimated?
100-age = cellularity (%)
What is the myeloid:erythroid ratio?
The relationship of neutrophils and precursors to proportion of nucleated red cell precursors
What does the myeloid:erythroid ratio range from?
1.5:1 to 3.3:1 - more myeloid cells because the lifespan of neutrophils is less than that of red cells.
Name a situation in which the myeloid:erythroid ratio might change?
Reversal in haemolysis as a compensatory response.
What are the 2 main categories of things which regulate haemopoiesis?
- Intrinsic properties of cells (e.g. stem cells vs progenitor cells vs mature cells).
- Signals from immediate surroundings and periphery (microenvironmental factors).
What does erythroid maturation occur around?
‘Nurse’ macrophages, in the form of islands - these provide nutrients
What is neutrophil and its precursor maturation regulated by?
G-CSF (granulocyte-colony stimulating factor)
What regulates the growth and development of megakaryocytes from their precursors?
Thrombopoietin.
What do haematopoietic stem cells occupy?
Occupy a ‘niche’ (anatomical site) – this provides signals for expansion, differentiation or dormancy
Where is the niche of haematopoietic stem cells found?
Around vasculature (arteriole or sinusoid) – provides access to different signals (cytokines)
When is a HSC’s niche altered?
In disease states or with therapy
What Ix’s are done for haemopoiesis?
- blood count.
- cell indices.
- morphology (blood film).
What is a less common test which Ix haemopoiesis?
- bone marrow examination
What test is sufficient when assessing mature cells?
Blood count/morphological assessment
What can be studied in mature cells, but is not generally required?
The expression of antigens indicating lineage or stage of development
What is immunophenotyping?
The study of antigen expression using specific antibodies
What is the challenge with assessing haemopoietic progenitor/stem cells?
They are morphologically indistinguishable cells
What tests can be used in the assessment of these rare populations of cells?
- Immunophenotyping
* Cytochemistry
What does immunophenotyping identify?
Patterns of protein (antigen) expression unique to a cell lineage.
What does immunophenotyping use to identify patterns of proteins?
Antibodies (in combination) specific to different antigens
