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Fundamentals of pathology > Origin of blood cells > Flashcards

Origin of blood cells Flashcards

1
Q

What is haematopoiesis?

A

Formation of red blood cells

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2
Q

How many red blood cells and neutrophils does each bone marrow produce?

A

○ 2x10^11 red blood cells

○ 5x10^10 neutrophils

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3
Q

What is required in haematopoiesis?

A

• Enormous levels of cell replication required

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4
Q

What is the pathway of haematopoiesis?

A

○ Stem cells–>Progenitors–>Precursors–>Mature red blood cells

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5
Q

Where are the sites where haematopoiesis occurs?

A 
• Sites:
        ○ Early embryo 
	○ Foetus
	○ Infant:
		§ Throughout bone marrow
	○ Adult:
		§ Central skeleton
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6
Q

What is the bone marrow and where is it located?

A
  • Spongy jelly like tissue

* Inside the bone

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7
Q

What does bone marrow have many of?

A

Many blood vessels to bring nutrients

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8
Q

What are the two types of bone marrow and what are there roles?

A

• Red marrow:
○ Active haematopoiesis
• Yellow marrow:
○ Filled with fat cells

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9
Q

What can be used to examine bone marrow architecture?

A

• Trephine biopsy used to examine bone marrow architecture

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10
Q

What can aspirate be used for?

A

○ Used to examine cellular morphology

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11
Q

What can you see in aspirate?

A

○ Can See mature cells plus many immature precursor cells

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12
Q

What are the commenest cells in aspirate?

A

○ Commonest cells are neutrophil precursors

§ Called myelocytes and myeloblasts

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13
Q

What is erythropoiesis?

A

• Formation of red blood cells when low levels of O2 detected

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14
Q

Platelet formation mechanism

A
  • Megakaryoblast undergo DNA replication however no cell division forming megakaryocyte
  • Megakaryocyte are large polypoid cells which remodel to form platelets
  • Platelets are formed and they’re cytoplasmic fragments
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15
Q

What is the pathway of lymphopoiesis?

A

○ Stem cell–>Common lymphoid progenitor–>T or B lymphocytes

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16
Q

Where does T cell formation occur?

A

Occurs in Thymus

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17
Q

Formation of T cell

A

○ Early progenitor migrates to thymus
○ T-cell receptor gene arrangement
○ Positive and negative selection

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18
Q

How are B cells formed?

A

○ Immunoglobulin rearrangement
○ Expression of surface IgM
○ Immature B-cell migrates to 2 degree lymphoid organs for maturation and antigen selection

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19
Q

Undifferentiated progenitors?

A

○ Cannot tell difference morphologically as they do not show characteristics of mature cells

20
Q

Committed progenitors

A

○ Already committed as to what they’ll become when they generate mature cells

21
Q

What do progenitors do in colony assays and thus what are they called?

A

○ Progenitors grow to form colonies of mature cells
○ From 32 to hundreds or thousands of cells in a colony
○ Thus progenitors called colony forming units(CFU)

22
Q

What do early progenitors do?

A

• Early erythroid progenitors grow to make large colonies that look like they have burst apart

23
Q

What do colony stimulating factors do?

A

• Colony stimulating factors stimulate colony growth

24
Q

Bone marrow transplantation steps

A
  • Completely ablate haemopoiesis with radiation and drugs
  • Infuse compatible donor marrow cells
  • Haemopoiesis can be completely restored
25
Q

What must the donor be in BMT?

A

• Donor must be HLA matched

Sibling or unrelated donor

26
Q

What is autologous BMT?

A

Where the patients own bone marrow is reinfused

27
Q

What can only give long term engraftment?

A

• Only Haematopoietic stem cells can give long term engraftment, not progenitors and precursors

28
Q

Risks of BMT

A

○ Significant mortality while waiting for engraftment
○ Infection due to neutropenia
○ Bleeding due to thrombocytopenia
○ Graft versus host disease

29
Q

Benefits of BMT

A

○ Only curative treatment for many diseases

30
Q

Pluripotent haematopoietic stem cells

A

Can give rise to cells of every blood lineage

31
Q

what are haematopoietic stem cells able to do?

A

• Self-maintaining:

○ Stem cell can divide to produce more stem cells

32
Q

Haematopoietic stem cells in mice

A

○ Mark stem cells by retrovirus insertion
○ Transplant irradiated mice with small number of stem cells

Same marked stem cells give rise to neutrophils, lymphocytes etc

33
Q

What is Chronic myeloid leukemia caused by and what does it affect?

A

○ Chronic myeloid leukaemia caused by a chromosome translocation in a stem cell
§ Mostly affects neutrophil lineage
§ Philadelphia chromosome also found in T-lymphocytes and other lineages

34
Q

What do stem cells and early progenitors carry?

A

• Stem cells and early progenitors carry cell surface antigen, CD34

35
Q

What do haematopoietic growth factors do?

A

• Polypeptide growth factors bind to cell surface transmembrane receptors

Stimulate growth and survival of progenitors

36
Q

Where are erythropoietin produced?

A

• Produced in kidney in response to hypoxia

37
Q

What do erythropoietin do?

A

• This increases red blood cell production by increasing survival of erythroid progenitors

38
Q

What are eryhtropoietin specific to?

A

• Specific to one lineage(erythroid)

39
Q

What do erythropoietin act on?

A

Acts on late progenitors

40
Q

What are the clinical applications of recombinant erythropoietin?

A

• Clinical applications of recombinant erythropoietin:
○ Treating anaemia of kidney failure
○ Alternative to blood transfusion for religious purposes

41
Q

What is G-CSF produced by?

A

G-CSF Produced by many cell types in response to inflammation

42
Q

What does G-CSF act on and promote?

A

• Acts on mature neutrophils in the periphery:
○ Chemoattractant
○ Promotes neutrophil maturation

Promotes neutrophil activation

43
Q

What does G-CSF stimulate?

A

• Stimulates neutrophil production in bone marrow
○ Stimulates neutrophil progenitors
○ Helps stimulate progenitors of other lineages, but only in combination with other growth factors

44
Q

Clinical applications of G-CSF

A

• Clinical applications:
○ Stimulate neutrophil recovery after bone marrow transplantation
○ Stimulate neutrophil recovery after chemotherapy
○ Treatment of hereditary neutropenia and other causes of neutropenia

45
Q

What other lineages does G-CSF stimulate?

A

• Stimulates other lineages like platelet recovery

46
Q

Peripheral blood stem cell transplantation?

A
  • G-CSF treatment causes stem cells to be released from the bone marrow into circulation
  • Seen by appearance of CD34+ cells in the circulation
  • Collected by leukapherisis
  • Used as an alternative to bone marrow for transplantation
  • Less traumatic for donor as anaesthetic not required.

Fundamentals of pathology (8 decks)

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