L1: Blood and bone marrow Flashcards
What is haematopoiesis?
- Mature blood cells generated from stem cell in bone marrow
- During stress (blood loss, infection) additional cell growth needed
- Regulated with precision but also responds to increased or decreased demands
Peripheral blood cell lineages (8)
Erythroid, neutrophil, monocyte/macrophage, eosinophil, basophil, megakaryocyte, T lymphoid, B lymphoid
Haematopoietic tissues
Tissue generating non-lymphoid tissue = haematopoietic tissue
- Bone marrow (95%): sternum, ribs, sacrum, vertebrae, long bones
- Spleen (5%)
Draw the 8 main lineages of blood cells
drawing
Origin of haematopoietic tissues
- Generated from mesoderm in blood islands of yolk sack (produce transient primitive blood cells)
- Definitive cells from endothelium in aorta-gonad-mesonephros (AGM) region
- Site of haematopoiesis then shifts to fetal liver, then to bone marrow
Haematopoietic tissue through life
Infancy: all bone marrow haematopoietic
Childhood: progressive fatty replacement of marrow throughout bones
Adult: haematopoetic marrow only in central skeleton (50% of marrow is fat)
- Fatty marrow can revert to haematopoiesis (in some blood disorders expansion into long bones)
- Spleen and liver can resume fetal haematopoietic roles (extramedullary, gives splenomegaly in myelofibrosis)
Bone marrow components
- Adult bone marrow: trabecular bone, fat cells and haematopoietic tissue
- Cellular component varies 30-70% (decreases with age)
- Main cells = haematopoietic cells, bone marrow stromal cells
Bone marrow stromal cells
- Fibroblasts, macrophages, fat cells, endothelial cells
- Physical support + impt for microenvironment suitable of blood cell production
- ECM, adhesion molecules, secretes blood cell growth factors
Haematopoietic stem cells
- Constitute v small fraction of total bone marrow/blood cel, production
- Stem cell properties: self-renewal, generation of one or more specialised cell types
- Human HSCs express antigen CD34 (used as measure of stem cell number)
Sources of HSCs
BM: under GA, BM harvest via needle aspirate from marrow space and retrieve 0.5-1L
Umbilical cord: rich source for transplantation (does not need to be as closely matched)
Peripheral blood: given haematopoietic GF, stimulates HSCs to move into peripheral blood
Mature haematopoietic cells
- Marrow represents a heterogeneous collection of cells without the stratification seen elsewhere (e.g. skin, gut)
- Series of maturing blood cell can be recognised for each lineage
- 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 circulating blood
Regulation of haematopoiesis
Requires precise regulation in steady-state and emergency: transcription factors and cytokines
Transcription factors: switched on and off, involved in stem cell development and erythropoiesis (Runx1, GATA-2)
Cytokine: growth factors control production of blood cells
- Stem cells and progenitors have receptors for GFs
- GFs produced by BM microenvironment
Dynamics of blood cell production
RBC - lifespan 120 days
Platelet - lifespan 5-6 days
Neutrophil - circulate 5-6 hours
Haemtopoietic GFs
Erythropoietin (EPO): stimulates RBC production
Thrombopoietin (TPO): stimulates platelet production
G-CSF: stimulates neutrophil production
Others: GM-CSF, multi-CSF (IL-3), M-CSF
Assessment of blood and marrow
Peripheral blood cells (FBC, CBC):
- Usually automated, absolute numbers of different cell types
- Blood film, morphology impt if abnormal parameters noted
Bone marrow examination:
- Aspirate for cytological examination of HSCs
- Trephine biopsy for histology (architecture, cellularity)
Stem cells:
- Can be assessed indirectly by colony assays and measurement of CD34 positive cells
