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Fundamentals of Pathology > W10 Origin of blood cells > Flashcards

W10 Origin of blood cells Flashcards

1
Q

Steps to mature blood cells

A

Stem cells > progenitors > precursors > mature blood cells

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2
Q

Each day the adult bone marrow produces

A

~2x1011 red blood cells

~5x1010 neutrophils

Plus smaller numbers of other cell types

Requires enormous levels of cell replication

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3
Q

Sites of haematopoiesis in infant

A

Throughout bone marrow

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4
Q

Sites of haematopoiesis in adult

A 
Central skeleton
vertebrae
ribs and sternum
skull
sacrum
pelvis
proximal ends of humerus and femur
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5
Q

Bone marrow

A

Spongy jelly like tissue
Inside the bone
Many blood vessels
- bring nutrients and take away new blood cells

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6
Q

Red marrow

A

Active haematopoiesis

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7
Q

Yellow marrow

A

Filled with fat cells

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8
Q

Bone marrow trephine

A

Trephine biopsy used to examine bone marrow architecture

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9
Q

Bone marrow aspirate

A

Used to examine cellular morphology

See mature cells plus many immature precursor cells

Commonest cells are neutrophil precursors, called myelocytes and myeloblasts

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10
Q

Blast cell

A

Blast- “seed” or “germ” cell

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11
Q

Basophil precursor

A

Basophilic myeloblast

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12
Q

Eosinophil precursor

A

Eosinophilic myeloblast

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13
Q

Erythropoiesis

A

Process which produces RBC

Proerythroblast > basophilic eryhtroblast > polychromatic erythroblast > pyknotic eryhtroblast > reticulocyte > mature RBC

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14
Q

Platelet formation

A

Megakaryoblast undergoes DNA replication but no cell division
Megakaryocyte formed which is a large polyploid cell
Cytoplasmic fragments then forming blood platelets

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15
Q

Lymphopoiesis

A

Stem cell converted into Common lymphoid progenitor

Then into T + B lymhocytes

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16
Q

T-cell formation in thymus

A

Early progenitor migrates to thymus
T-cell receptor gene rearrangement
Positive & negative selection

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17
Q

B-cell formation in bone marrow

A

Immunoglobulin gene rearrangement
expression of surface IgM
Immature B-cell migrates to 2prime lymphoid organs for maturation and antigen selection

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18
Q

Undifferentiated progenitors

A

You cannot tell the difference between them morphologically because they do not show the characteristics of mature cells

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19
Q

Committed progenitors

A

They are already committed as to what they will become when they generate mature cells

20
Q

Colony assays process

A

Singe cell suspension of bone marrow which is then incubated for 7-14 days in semi-solid medium (agar, methylcellulose) w/growth factors

21
Q

Colony assays

A

Progenitors grow to form colonies of mature cells
From 32 to hundreds or thousands of cells in a colony
Thus progenitors are called “Colony Forming Units” -CFU

Used to study the proliferation and differentiation pattern of hematopoietic progenitors

22
Q

Colony assays types

A 
CFU-G (neutrophilic) granulocyte progenitor
CFU-GM granulocyte/monocyte progenitor
CFU-E  erythroid progenitor 
CFU-Mk
CFU-bas
CFU-eo
23
Q

Burst forming unit - erythroid

A

Early erythroid progenitors grow to make large colonies that look like they have burst apart
Thus the name BFU-E (burst forming unit- erythroid)

24
Q

CSF

A

Factors which were discovered to stimulate colony growth were named colony stimulating factors (CSF) e.g.
G-CSF granulocyte-CSF
M-CSF monocyte-CSF
GM-CSF

25
Q

Bone marrow transplantation

A

completely ablate haemopoiesis with radiation and drugs
infuse compatible donor bone marrow cells
haemopoiesis can be completely restored

26
Q

BMT donor

A

Donor must be HLA matched
sibling or unrelated donor

Or autologous BMT (cells or tissues obtained from the same individual)
reinfuse patients own bone marrow

27
Q

BMT engraftment

A

Only haematopoietic stem cells can give long term engraftment
NOT progenitors
NOT precursors

28
Q

BMT applications

A

Leukaemia, lymphoma, myeloma
Intensified chemotherapy for solid tumours
Genetic diseases e.g. thalassaemia, SCID etc

29
Q

BMT risks

A

significant mortality while waiting for engraftment

infection due to neutropenia (low neutrophil count)

bleeding due to thrombocytopenia (low platelets)

Graft versus Host Disease (GVHD)

30
Q

BMT benefits

A

For many diseases, this is the only curative treatment

31
Q

Pluripotent

A

Can give rise to cells of every blood lineage

32
Q

Self maintaining

A

A stem cell can divide to produce more stem cells

33
Q

Mice (stem cells)

A

mark stem cells by retrovirus insertion

transplant irradiated mice with small number of stem cells

same marked stem cell gives rise to neutrophils, lymphocytes etc

34
Q

CML

A

Human
Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in a stem cell

disease mostly affects neutrophil lineage
but Philadelphia chromosome also found in T-lymphocytes and other lineages.

35
Q

CD34

A

Stem cells and early progenitors carry the cell surface antigen CD34

Later progenitors = CD34 +ve

Immature precursors = CD34 -ve

Use to purify stem and progenitor cells

36
Q

HAEMATOPOIETIC GROWTH FACTORS

A

Polypeptide growth factors (cytokines)

Bind to cell surface transmembrane receptors

Stimulate growth and survival of progenitors

37
Q

HAEMATOPOIETIC GROWTH FACTORS - specific/stim

A

some stimulate early progenitors,
e.g. Il-3, stem cell factor (SCF)

others stimulate late progenitors
e.g. M-CSF (monocyte-CSF)

some are specific to one lineage
e.g. erythropoietin
others stimulate several different lineages

38
Q

Erythropoietin

A

Produced in the kidney
In response to hypoxia
Increases red blood cell production by increasing survival of erythroid progenitors (CFU-E)

Specific to one lineage (erythroid)

Acts on late progenitors

39
Q

Clinical applications of recombinant erythropoietin

A

Treating anaemia of kidney failure

Alternative to blood transfusion in Jehovah’s Witnesses

40
Q

G-CSF

A

Produced by many cell types

In response to inflammation

Granulocyte colony stimulating factor

41
Q

G-CSF - acts on mature neutrophils in the periphery

A

chemoattractant
promotes neutrophil maturation
promotes neutrophil activation

42
Q

G-CSF - Stimulates neutrophil production in the bone marrow

A

Stimulates neutrophil progenitors (CFU-G)

Helps stimulate progenitors of other lineages, but only in combination with other growth factors

43
Q

G-CSF - clinical applications

A

stimulate neutrophil recovery after bone marrow transplantation

stimulate neutrophil recovery after chemotherapy

treatment of hereditary neutropenia and other causes of neutropenia

because G-CSF also helps to stimulate other lineages, it will also (for example) stimulate platelet recovery after bone marrow transplantation

44
Q

Peripheral blood stem cell transplantation

A

G-CSF treatment causes stem cells to be released from the bone marrow into the circulation
Seen by appearance of CD34 + cells in the circulation
Collect by leukapheresis

45
Q

Peripheral blood stem cell transplantation - advantages

A

Used an alternative to bone marrow for transplantation

Less traumatic for donor, no general anaesthetic

Fundamentals of Pathology (23 decks)

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