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Y4S1 - Haematology > W4L7 - Haematopoiesis & Bone Marrow > Flashcards

W4L7 - Haematopoiesis & Bone Marrow Flashcards

1
Q

Haematopoiesis

A

The production of the cellular elements of the blood
Haematopoietic cells are derived from haematopoietic stem cells (HSC)
HSC must be able to:
- reproduce themselves in a process of self-renewal
- others differentiate to formed mature blood cells
Haematopoiesis can only occur in specialised sites

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2
Q

Haematopoietic Niche

A

Haematopoiesis can only occur in a protected environment known as the ‘haematopoietic niche’
The haematopoietic niche provides:
- soluble cytokines
- cell-cell contacts
- insoluble extra-cellular matrix
A lack of any of these components will impair the development of haematopoietic stem cells (HSC)
In the adult bone marrow there is a low frequency of HSCs, with two to five HSCs per 105 total bone marrow cells

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3
Q

Soluble Factors

A 
The proliferation & differentiation of mature blood cells is controlled by many soluble haematopoietic growth factors
- stem cell factor
- colony stimulating factors (CSFs)
- interleukins (IL-1 to 11)
WBC
- granulocyte (macrophage CSF)
- granulocyte CSF
- macrophage CSF
RBC
- erythropoietin
Megakaryocytes/platelets
- IL-6
- thrombopoietin
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4
Q

Cells Present in the Haematopoietic Niche

A 
Mesenchymal stem/stromal cells
Osteoblast, osteoclast
Schwann-like cells
Endothelial cells
Nestin+ mesenchymal cells
Adipocytes
Macrophages
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5
Q

Haematopoietic Niche Role

A

Important role of niche cells to regulate
- survival, self renewal, migration and differentiation of HSC
Mechanisms
- cell contact interactions
- production of growth factors (cytokines, chemokines)
- production of extracellular matrix molecules (ECM)

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6
Q

Haematopoietic Stem Cells

A

LSK (Lin– SCA1+ KIT+) HSC
Three ‘sub-populations’:
1. Long-term repopulating (LTHSC)
2. Short-term repopulating (STHSC)
3. Multi-potential progenitor (MPP) => differentiate
All show different gene expression patterns
100 LSK HSC can provide protection from lethal irradiation
Can also circulate in peripheral blood at low concentration

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7
Q

Haematopoietic Stem Cells - How to Increase Circulating Numbers

A

Administration of exogenous growth factors

For example, granulocyte colony stimulating factor (G-CSF) can be used clinically as a mobiliser of HSC

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8
Q

Automated Haematology Analysers

A

E.g. Sysmex analysers
HPC: haematopoietic precursor cells = CD34+ HSC
Used to determine numbers of HPC in peripheral blood

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9
Q

Why is Apoptosis Required in Haematopoiesis?

A

Counter-balance cell proliferation, i.e. remove cells excess to requirement
Remove imperfect/damaged cells - potentially dangerous if clonal expansion

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10
Q

Active Haematopoiesis

A 
Foetus
- 0-2 months - yolk sac
- 2-7 months - liver, spleen
- 5-9 months - bone marrow, thymus
Infants
- widespread bone marrow
- thymus
Adults
- vertebrae
- ribs
- sternum
- skull
- pelvis
- femur
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11
Q

Extra-Medullary Haematopoiesis

A 
Haematopoiesis that occurs ‘outside’ the bone marrow
May occur in a range of tissues
Typical sites include:
- spleen
- liver
- lung
- lymph node
Atypical sites:
- may occur in any location
Detected by imaging and biopsy
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12
Q

Bone Marrow Components

A 
Haematopoietic cells
- erythroid
- myeloid
- lymphoid
- megakaryocytic
Fat cells (adipocytes)
Stromal cells
- mesenchymal population
Endothelial cells
- capillaries
- venules
- sinusoids
Bone cells
- osteoblasts
- osteoclasts
Macrophages
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13
Q

Bone Marrow - Normal Characteristics

A 
Mixed adipose & haematopoietic tissue
All cell lines represented
- erythroid, myeloid, megakaryocytic
Myeloid:Erythroid ratio 1.5 - 4.0 : 1
Orderly maturation sequence
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14
Q

Erythropoiesis in Bone Marrow

A

Occurs in within erythroblastic islands (E.I.) within the bone marrow
Range of stages of erythroid development present within E.I.
Central iron-containing macrophage (‘nurse’ cell) provides iron for haeme formation

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15
Q

Enucleation of RBC Precursors

A 
Orthochromic normoblasts
Occurs within bone marrow
Mediated by microtubules & actin-myosin
Rapid process (~10 minutes)
Produces:
- reticulocyte
- pyrenocyte
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16
Q

Morphological Changes with Maturation - Granulocytopoiesis

A

Myeloid cells become smaller
N:C ratio decreases
Nucleus
- nucleus becomes smaller & segments form
- nucleolus disappears
- chromatin pattern becomes denser
Cytoplasm
- becomes lighter (less basophilic) in colour
- (specific/secondary) granules form & increase density

17
Q

Haematopoiesis - Monocytopoiesis

A

Monocytes develop from the pluripotent stem cell, via the myeloid stem cell
Monocytic precursors not typically found in the peripheral blood
Developmental stages:
- monoblast
- promonocyte
- monocyte

18
Q

Megakaryocytopoiesis / Thrombopoiesis

A

Stages of development
- megakaryoblast
- promegakaryocyte
- megakaryocyte (largest cell in bone marrow and have many nuclei)
- mature platelet (cytoplasmic fragments from megakaryocyte)
Megakaryocytes are resident in the bone marrow
From megakaryoblast to megakaryocyte, these are present in bone marrow, whereas mature platelets found in circulation
Thrombopoietin primarily influences the production & maturation
Megakaryoblast to platelets take ~5 days

19
Q

Platelets Information

A

Average lifespan ~ 9.5 days
~2/3 circulate in the blood
~1/3 sequestered in the spleen
Early release platelets are larger than more mature platelets, often contain RNA

20
Q

Haematopoiesis - Lymphopoiesis

A 
Stages of lymphocyte development
- lymphoblast
- prolymphocyte
- lymphocyte (small lymphocyte, large lymphocyte)
B lymphocyte => plasma cell
21
Q

Clinical Assessment of Bone Marrow

A

Must be interpreted with a concurrent FBC
Consider:
- cellularity
- cells present
- relative numbers of 3 cell lines; e.g. M:E
- maturation sequence (orderly?)
- cell morphology

22
Q

Bone Marrow - Decreased Production

A 
‘Hypoproliferative disorders’
- erythroid hypoplasia
- myeloid hypoplasia
- megakaryocytic hypoplasia
Combined hypoplasia (2 or 3 lines)
- bilineage hypoplasia
- trilineage hypoplasia
Reflected in the peripheral blood
- anaemia
- leukopenia
- thrombocytopenia
- bicytopenia
- pancytopenia
23
Q

Pancytopenia

A

Typical profile for a patient receiving myelosuppressive therapy
Severe reduction in the neutrophil count
Moderate normocytic anaemia
Thrombocytopenia

24
Q

Bone Marrow - Reasons for Decreased Production

A 
Congenital
- fanconi anaemia 
Autoimmune disease
- pure red cell aplasia
- idiopathic aplastic anaemia
Radiation, chemical, drugs
- cytotoxic chemotherapeutic agents
- lithium
- choramphenicol
25
Q

Bone Marrow - Increased Production

A 
‘Hyperproliferative disorders’
- erythroid hyperplasia
- myeloid hyperplasia
- megakaryocytic hyperplasia
Combined hyperplasia (2 or 3 lines)
- bilineage hyperplasia
- trilineage hyperplasia
Reflected in the peripheral blood
- erythrocytosis
- leukocytosis
- thrombocytosis
26
Q

Bone Marrow - Increased Production due to Reactive Changes

A

Appropriate production i.e. in response to stimulus
E.g. myeloid hyperplasia in response to inflammation
- IL-1, IL-6 => increased myelopoiesis, increased M:E
E.g. erythroid hyperplasia in response to anaemia
- Epo => increased erythropoiesis, decreased M:E

27
Q

Bone Marrow - Increased Production due to Neoplastic Changes

A 
Inappropriate production
Spectrum of malignancy
Myelodysplasia
Myeloproliferation
Leukaemia
28
Q

What do the Niche cells do with HSCs?

A

Niche cells act to control HSC
Effects
- cause cells to become quiescent/inactive and act as a storage
- promote self renewal
- promote asymmetrical division => differentiation

29
Q

Stages of Erythropoiesis

A
  1. Pronormoblast
  2. Basophilic normoblast
  3. Polychromatophilic normoblast
  4. Orthochromic normoblast
    - final stage with a nucleus
  5. Reticulocyte (polychromatophilic RBC)
  6. Mature RBC
30
Q

Stages of Granulocytopoiesis

A
  1. Myeloblast
  2. Promyelocyte
    - myeloblast and promyelocyte don’t have distinguishing features that tells us whether it will form a neutrophil, eosinophil or basophil
  3. Myelocyte
  4. Metamyelocyte
  5. Band nucleus
  6. Mature granulocytes
    - neutrophils, eosinophils, basophils

Y4S1 - Haematology (22 decks)

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