Haematology (Haemopoiesis and the bone marrow) Flashcards
How many blood cells are produced in the bone marrow each day in healthy individuals?
5-10 x 10^11
Where does haemopoiesis commonly occur? What other places can it occur in?
In the bone marrow
- In certain pathological conditions it can occur in tissue (liver, lymph nodes, spleen)
- In neonates can occur in the embryonic yolk sac
How long after gestation does the bone marrow take over haemopoiesis?
5-9 months
In infacts, what bones does haemopoiesis occur in?
- Axial skeleton
- Proximal ends of long bones e.g femur
In adults, what bones are the locations for haemopoiesis?
- Sternum and iliac crests
- Skull, vertebrae and ribs may be involved
What are the 3 main structures of the bone marrow? Briefly describe each
1) Haemopoietic cells
- sometimes known as cords
2) Sinuses
- consist of vascular spaces that are lined with endothelial cells to regulate the release of mature blood cells
3) Non-haemopoietic cells
- Tissues that:
> support the bone marrow structure e.g stromal cells such as fibroblasts
> Produce growth factors e.g macrophages
> Store fat e.g adipocytes
What are pluripotent stem cells and what do they become?
A common primitive stem cell in the bone marrow
- can differentiate into lineage-specific stem cells e.g the common myeloid and common lymphoid progenitors
How easy is it to differentiate pluripotent stem cells from mature cells?
Almost impossible
How can linage-specific stem cells be differentiated from mature cells?
Presence of surface markers such as CD34
What are stem cells sometimes known as?
Colony forming units
Regulation of haemopoiesis is controlled by what?
Colony-stimulating factors (CSFs)
- function like cytokines
How does granulocyte-macrophage CSF (GM-CSF) work?
Can non-specifically stimulate the differentiation of all blood cells
Give some examples of growth factors that are lineage specific
- Erythropoietin (EPO) - red blood cell lineage
- Thrombopoietin (TPO) - platelet lineage
Describe the process of erythropoiesis
1) Pathway starts with common myeloid precursor CFU-GEMM
2) CFU-GEMM gives rise to the megakaryocytic precursor (CFU-Emk)
3) CFU-Emk produces the red cell lineage-specific stem cell CFU-E
4) CFU-E develops into the proerythroblast and divisions reduce its size to a nucleated RBC
5) Loss of nucleus results in generation of a juvenile RBC known as a reticulocyte
6) Maturation occurs over 3-4 days to mature RBC
What immune cells are the granulocytes?
Neutrophils, eosinophils and basophils
Describe the process of granulopoiesis
CFU-GEMM develops into 4 CFUs:
- CFU-baso
- CFU-neut
- CFU-eos
- CFU-M (monocyte precursor)
At what stage can lineage-specific precursors of mature granulocytes be recognised?
The myelocyte stage
How can these myelocyte stage granulocyte precursors be recognised?
Staining of their granules
What enzymes and molecules can be found within the granules?
- myeloperoxidase
- collagenase
- heparin
- lactoferrin
- histamine
Describe the process of thrombopoiesis
- Lineage-specific progenitor cell CFU-MK develops into the megakaryoblast and then onto the megakaryocyte
- Megakaryocytes produce pseudopodial projections of the cytoplasm called proplatelets across the endothelial layer of blood vessels
- The force of the blood cause proplatelets to break off into circulation
- Proplatelets differentiate into platelets by twisting and pinching as midline
What are the typical serum levels of platelets? What can affect this number?
100 pg/L
- can increase in throbocytopenia, aplastic anemia and in acute inflammation
How many platelets are produced each day?
10^11
What occurs are production of 1,500-4,000 platelets from one megakarocyte?
Nothing remains but the nucleus
- phagocytosed by bone marrow macrophages
Describe the production of monocytes
- Common precursor with granulocytes (CFU-Gmo)
- Becomes 2 species of immature monocyte:
- monoblast
- promonocyte
- Promonocytes develop into mature monocytes that enter blood
What happens to monocytes after a few days in circulation?
Become macrophages
What are some specialized APCs that some macrophages develop into
1) Langerhans cells (spleen)
2) Kupffer cells (liver)
3) Interdigitating dendritic cells (all tissues)
Describe the production of lymphocytes
- Common lymphoid progenitor (CFU-L) gives rise to immature lymphoblasts which deifferentiate into mature lymphocytes; B cells, T cells and NK cells
What is the M/E ratio? What should it be in healthy adults?
Ratio of myeloid (M) precursors to erythroid (E) precursors
approx 3-4:1 in healthy adults
Name some diseases associated with an increased or reduced M/E ratio
Increased
- Myeloid leukaemia
- Most infections
Reduced:
- Suppressed myelopoiesis e.g chemo, viral infection
- Enhanced erythopoiesis
e. g blood loss, iron deficiency
What is cytochemistry and what is it primarily used for?
- Exploits the way that components of the cytoplasm react with dyes (e.g granules)
- Used to detemine identity and number of WBCs and their precursors
What is flow cytometry primarily used for?
Used to assess cell populations based on molecules on the cell surface
- Uses monoclonal antibodies conjugated to a fluorochrome to defined cell surface antigens e.g CD34
Name some CDs that can be found on B cells, T cells, myeloid cells, monocytes, haemopoietic precursors and WBCs
T: CD2, CD3 B: CD10, CD20 Myeloid: CD13, CD33 Monocytes: CD14 Stem cells: CD34 WBCs: CD45
