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Pathology 1 > Haematopoiesis > Flashcards

Haematopoiesis Flashcards

1
Q

What are growth factors?

A

Polypeptides that control replication and survival vs. death throughout the various stages of blood cell formation

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2
Q

Name the neutrophil precursors

A 
Myeloblasts 
Promyelocyte 
Myelocyte 
Metamyelocyte 
Band
Segmented neutrophil
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3
Q

What is myelopoiesis?

A

Formation of bone marrow

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4
Q

What are myeloblasts?

A

Bone marrow progenitor cells

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5
Q

Outline the stages of platelet formation

A
  1. DNA replication occurs in megakaryoblasts
    • but no cell division
  2. Megakaryocytes formed
    • large polypoid cells
  3. Cytoplasmic fragments bud off to form platelets
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6
Q

What is lymphopoiesis?

A

Generation of lymphocytes

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7
Q

Describe the cells needed for initiating blood cell formation

A

Blood cell formation starts from a small no. of stem cells in bone marrow
–> pluripotent stem cells
–> specific to blood cells and can give rise to early
progenitors

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8
Q

What are the requirements of a bone marrow transplant donor?

A 
Must be (human lymhocyte antigen) HLA matched 
Can be un/related or autologous (reinfuse patients own bone marrow)
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9
Q

Daily, how many blood cells are produced?

A

RBCs ~ 2x10¹¹
Neutrophils ~ 5x10¹⁰
Smaller no. of other cell types

There’s a constant high level of blood cells production requiring a lot of cell replication

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10
Q

Describe how a bone marrow transplant works

A
  • Completely ablate haemopoiesis with radiation and
    drugs
  • Infuse compatible donor bone marrow
  • Haemopoiesis completely restored

Only haematopoietic stem cells give permanent engraftment - not progenitors or precursors

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11
Q

What are the different types of myeloblasts?

A

Basophilic myeloblasts

Eosinophilic myeloblasts

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12
Q

What are CSFs?

A

Colony stimulating factors that stimulate colony growth

e.g. G-CSF (granulocyte-CSF)

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13
Q

Outline the stages of haematopoiesis

A

early progenitors –> late progenitors –> immature precursors –> mature blood cells

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14
Q

How are lymphocytes formed from stem cells?

A

Stem cells decide whether to differentiate into lymphocytes or myeloid cells
Once committed to becoming a lymphocyte, stem cells form either:
T- Lymphocytes (in Thymus)
B- Lymphocytes (in Bone marrow)
involving positive feedback loops with the correct transcription factors present

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15
Q

What is erythropoiesis?

A

Eryhtrocyte formation

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16
Q

Name the different types of CFUs

A
  • CFU-G (neutrophilic granulocyte progenitor)
  • CFU-GM (granulocyte/monoprogenitor)
  • CFU-E (erythroid progenitor)
  • CFU-MK
  • CFU-bas
  • CFU-eo
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17
Q

How is Haematopoiesis regulated?

A

Haematopoiesis is regulated by growth factors

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18
Q

Name the precursors of platelet formation

A

megakaryoblasts –> megakaryocyte –> blood platelets

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19
Q

What are BFU-Es?

A

Early erythroid progenitors produce colonies that look as though they’ve been burst apart
AKA BFU-E (burst forming unit - erythroid)

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20
Q

How can we examine bone marrow structure?

A

Using Trephine Biopsy
Aspirate for more detail
- used to examine cellular morphology
- can see both precursors and mature cells

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21
Q

Describe the devlopment of erythrocyte precursors in the bone marrow

A

As erythrocytes develop, cytoplasm becomes pinker in colour as Hb produced and nucleus becomes smaller
Erythroblasts leave bone marrow, leaving nucleus behind forming RBC

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22
Q

How are T cells formed?

A
  1. Early progenitor migrates to thymus once committed to
    T cell lineage
  2. T cell receptor gene arrangement
  3. Positive and negative selection occurs
23
Q

Where does haematopoiesis occur in the early embryonic state?

A

Haematopoiesis takes place in the yolk sac

(yolk sac - embryonic structure outside the main embryo) in placenta

24
Q

What type of process is haematpoiesis?

A

Irreversible, one way process

25
Q

What are the risks of Bone marrow transplants?

A

Mortality while waiting for engraftment
Infection due to neutropenia
Bleeding due to thrombocytopenia
Graft vs Host Disease

26
Q

Why is it important to measure reticulocyte production in bone marrow?

A

Increased amount of reticulocytes in marrow means cells are working overtime to produce
RBCs - diagnostic of haemolytic anaemia

27
Q

What are the applications of Bone Marrow Transplant?

A
  • leukaemia, lymphoma, myeloma
  • intensified chemotherapy for solid tmours
  • genetic diseases (thalassemia, SCIID etc.)
28
Q

What is the benefit of stem cells’ individual ability to initiate their own replication?

A

Acts as an anticancer mechanism
- prevents cells undergoing genetic damage when
replicating including the activation of oncogenes

Ensures most cells that replicate are committed to terminal differentiation

29
Q

What are the important features of progenitors?

A

Undifferentiated
- unidentifiable morphologically as no mature cell
characteristics present yet

Committed
- Already committed to which mature cells they’ll
generate

30
Q

How does B cell formation occur?

A
  1. Immunoglobulin gene rearrangement occurs
  2. Expression of surface immunoglobulin (IgM) on
    membrane
  3. Immature B cells migrates to secondary lymphoid
    organs for maturation & antigen selection
31
Q

What are immature red blood cells called?

A

Reticulocytes

32
Q

Describe how colony assays can be used to grow a colony of mature cells

A
  1. Growth factors in semi solid medium (agar)
  2. A progenitor cell with correct growth factor will grow
    into a colony of one lineage
  3. Progenitors grow to form mature cell colonies from 32-
    1000’s of cells
- progenitors are therefore also known as Colony 
  Forming Units (CFUs)
33
Q

What is the role of stem cells in mice?

A
  • Mark cells via retrovirus insertion
  • Transplant irradiated mice with small no. of stem cells
  • Same marked stem cells give rise to neutrophils,
    lymphocytes etc.
34
Q

In a foetus, where does haematopoiesis occur?

A

In the foetal liver - very red haematical vital organ

35
Q

How can stem cells cause leukaemia in humans?

A

Can cause chronic myeloid leukaemia (CML) caused by a chromosome translocation on small chromosome 22 and large 23
found in T cell lineages
most produce excess neutrophils
Stimulates myeloid cell production

36
Q

What are the advantages of Bone marrow transplant?

A

Only curative treatment available for many diseases

37
Q

During infancy where does haematopoiesis happen?

A

Occurs throughout the bone marrow

38
Q

What type of stem cells are haematopoietic cells?

A

Pluripotent and self maintaining

39
Q

Outline how blood cells are formed

A

Stem cells -> progenitors -> precursors -> mature blood cells

40
Q

List some G-CSF applications

A
  • neutrophil recovery after BMT/chemo
  • hereditary neutropenia
  • stimulates platelet recovery as stimulates other lineages
    (only in combination with other growth factors)
41
Q

When do blood cells become differentiable?

A

Stem cells & progenitors can’t be distinguished morphologically as there is no real difference between them
Precursors begin looking like mature cells
Mature cells are easily identifiable via their morphology

42
Q

How do haematopoietic growth factors work?

A

Cytokines (polypeptides) bind to cell surface membrane receptors
Stimulating growth and progenitor survival

43
Q

What is erythropoietin?

A

EPO is a hormone produced in the kidney, in response to hypoxia

44
Q

How are stem and progenitor cells purified?

A

Stem cells and early progenitors carry cell surface antigen CD34 used to purify them

45
Q

Where does blood cell formtaion occur in adults?

A

Haematopoiesis is limited to the central skeleton under normal conditions which includes:

  • vertebrae
  • ribs & sternum
  • skull
  • sacrum
  • pelvis
  • proximal ends of humerus & femur
46
Q

What is the advantage of Peripheral blood stem cell transplantation?

A

Less traumatic alternative to bone marrow transplantation , no general anaesthetic needed

47
Q

What is the role of eryhtropoietin?

A

Increases RBC production via increase of progenitor survivor using CFU-E
Speciifc to lineage; acts on late progenitors

48
Q

When are G-CSF produced?

A

Granulocyte colony stiumlating factors are produced by many cell types in response to inflammation

49
Q

What are the different types of blood vessels?

A

Red marrow - Active haematopoiesis - contains lots of eyrhtrocytes

Yellow marrow - filled with fat cells

50
Q

What is haematopoiesis?

A

Formation of blood cells

51
Q

How is G-CSF used in peripheral blood stem cell transplantation?

A

G-CSF causes stem cells to be released from the bone marrow into circulation
Seen by appearnce of CD34 and cells in circulation
Collected by leukapheresis

52
Q

What are the clinical applications of recombinant erythropoietin?

A
  • Treatment of anaemia kidney failure

- Alternative to blood transfusion

53
Q

What is bone marrow?

A

A spongy jelly like tissue inside the bone that is highly metabolically active
Contains many blood vessels to bring nutrients in and take away new blood vessels

54
Q

How do G-CSFs work?

A

Acts on mature neutrophils in periphery as a chemoattractant promoting neutrophil
activation and maturation.
Also stimulates neutrophil production in bone marrow by stimulating neutrophil progenitors CFU-G

Pathology 1 (20 decks)

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