The Blood and Bone Marrow Flashcards
What is this and what is it from?
A Petechial Haemorrage.
A small bleed from a ruptured capillary vessel
What do blood cells originate as ?
Derived from stem cells, then differentiate into a mature blood cell via influence of cytokines.
What is Haematopoiesis and when doe this occur??
Haematopoiesis: Process by which mature blood cells are generated from stem cells in bone marrow
- As mature blood cells are usually short-lived, this process is reqired constantly
- Neutrophil 12-24 lifespan then → pus
- excuberated during stress (blood loss, infection)
- Nededs to be regulated with precise precision as circulating levels of mature cells are maintained within narrow limits of variation
but cell production can be altered rapidly in response to inc/decr demand!
describe the components of a centrifuged blood sample
- Yellow/clear substance: Plasma Serum containing all the proteins
- White blood cells
- Red Blood cells: go to bottom as they are heavier
** this patients WBC layer is too large as they have leukaemia!
What’s the Clinical Important of Studying Haematopoiesis?
- Blood tests important for patient management
- Diagnosis and monitering
- Understanding the function of Blood cells
- intrprets investigations
- diagnosis/management of blood disorders; anaemia and leukaemia
What are the Haematopoietic Tissues?
Really just the blood cells!
- Peripheral Blood Cells: derived from 8 main lineages
- Erythroid, neutrophil, monocyte/macrophage, eosinophil (release granules in response to inflammatory system; eg asthma), basophil, megakaryocyte (flake off in blood), T lymphoid, B lymphoid (WBCs)
- Also Adult tissues that are generating non-lymphoid cells of the blood!
- bone marrow (95%); sternum, ribs, sacrum, vertebrae, top of long bones
- Spleen (5%) ; has to take over in myofibrosis
Haematopoietic Stem cells is self renewing
- Also can go on to form colony renewing cell of the liver
- Huge proliferative potential earlier; and none at the end!
- Know this diagram!
Describe the Haematopoietic Stem Cell Niches
- Begin as an endothelial niche
- this primitive cell then migrates to it’s endosteal Niche (next to bone marrow)
- Become Haematopoietic Stem Cell that is Self Renewing or Differentiating
Origin of Haematopietic Tissues
Generated from the mesoderm of blood islands of the yolk sac (to produce transient ‘primitive’ blood cells) and then ‘definitive’ cells from endothelium in the AGM (aorta-gonad-mesonephros) region
- Site of haematopoiesis then shifts to the fetal liver → bone marrow
- The Placenta, AGM and Yolk sac contribute these cells to the fetal liver, which only makes its way to the bone marrow in the 3rd trimester
How much Haematopoietic Tissue is in the Bone Marrow at differing stages of life?
- Infancy: all the bone marrow is haematopoietic
- Childhood: progressive fatty replacement of marrow thorughout the long bones
- Adulthood: now the haematopoirtic marrow is confined to the central skeleton
- 50% of marrow is fat in adults
Fatty marrow is capable of reversion to _________
Fatty marrow is capable of reversion to haematopoesis!
In some blood disorders there is also expansion of haematopoisesis into the long bones
The spleen and liver can also resume their fetal haematopoietic roles; ‘Extramedullary haematopoiesis’
Mylofibrosis; Spleenomegaly
Bone Marrow gets ‘scarred up’ with collagen and reticulum.
Normally spleen is not palpable and hidden under you left ribcage
This spleen is way down into the pelvis, past the umbilicus
Causes Early Satiety; low appetite → weight loss
Bone Marrow Constituents
- Adult Bone Marrow: trabecular bone containing fat and haematopoietic tissue in variable quantities
- Cellularity 30-70% and decreases with age
- Major cellular elements; haematopoietic cells and bone marrow stromal cells
Stromal Cells Include?..
What are their roles?
Fibroblasts, macrophages, fat cells and endothelial cells
- Provide physical support and a microenvironment for blood cell production
- this microenvironment produces ECM, adhesion molecules and secretes blood cell growth factor
Describe the Appearance of Bone Marrow
- Trabecular bone
- Fat spaces in adult bone
- Haematopoietic cells: purple little cells (with nucleus), RBC are red as no nucleus
- Stromal cells
HSC (Haematopoietic Stem cells) sustain haematopoiesis but constitute what fraction of total bone marrow blood cell population?
What are their properties?
HSCs: 1/10,000-100,000 of the total bone marrow blood cell population
Stem Cell Properties:
- Self Renewal
- Generation of one or more specialised cell types
Human HSCs express the antigen ______ and what is this used for??
Express antigen CD34 and this is used as a measure of stem cell number , particularly when measuring cells for transplantation
Stem cells can be taken from one arm, centrifuged and everything but stem cells returned to the other arm
**Umbilical cord blood is enriched in HSCs are therefore used increasingly as a source of stem cells for transplantation; especially within paediatrics
How do we make the stem cells come into the blood stream prior to stem cell removal and transportation?
The donater is given special injections of Granulocyte colony stimulating factors for four days. These make the adhesion molecules in the bone marrow ‘let go’ and the stem cells be released into the blood stream and then we can catch them by leukophoresis
Mature Blood Cells can be seen in…..
- They form a heterogeneous collection of cells without the stratification seen; eg; in the skin or gut, lots of different stages of development!
- Despite this, series of maturing blood cells can be recognised for each lineage.
- In general, only the most mature cells in each lineage enter the circulation in significant number, although small numbers of stem cells and progenitors are present
How does the HSC know to differentiate down this pathway??
Because of transcription factors; most notably Runx-1 and GATA-2
Cytokine regulation of Haematopoiesis
platelets driven by : Thrombopoietin (TPO)
Monocytes, Neutrophils, Eosinophils driven by : GM-CSF
For neutrophil recovery and to drive stem cells into the blood
Red cells/eurythropoietin is driven by: EPO
How do you Assess Blood and Bone Marrow?
- Peripheral Blood Cells: full/complete blood count (FBC, CBC)
- Usually automated; gives absolute # of each cell type
- If abnormal; examination of blood film to look carefully at morphology is important if abnormal parameters are noted!
- Bone Marrow Examination (ouch)
- BM aspirate allows cytological examination of haematopoietic cells
- BM trephine produces a core biopsy which is good for histological examination of marrow architecture and cellularity
- Stem Cells: can be assesed indirectly (colony assays) or measurement of CD34 + cells
- Bone Marrow aspirate shows: hyercellular marrow with homogenous population of blast cells and little differentiature to mature myeloid forms
Diagnosis: Acute Myeloid Leukemia
Treatment: Chemotherapy, transfusion support and ABs for infection
