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Year One: Pesky Things > Haematopoiesis > Flashcards

Haematopoiesis Flashcards

1
Q

Define haematopoiesis(3)

A

 Production of red blood cells, white blood cells and platelets from HSC.
 Highly regulated to maintain circulating cell numbers within relatively constant level
 Decisions are made (determination) which tell the cell into which lineage they’re going to.

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2
Q

What is the site of haematopoiesis in the foetus?

A

The yolk sac, the liver then the spleen are important for foetal life but after birth it is restricted to the bone marrow

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3
Q

Where are the sites of haematopoiesis during pregnancy?

A

 First trimester: Yolk Sac
 Second trimester: Liver & Spleen
 Third trimester: Central, Peripheral skeleton

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4
Q

Where does haematopoiesis take place in adults?

A 
Axial Skeleton
	Vertebral bones
	Sternum
	Ribs
	Pelvics
	Haematopoiesis may re-expand to foetal sites in times of severe demand; e.g. thal, MF(Myelofibrosis cancer)
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5
Q

What happens to the marrow cavities as we age?

A

As we age, the quantity of this haematopoietic tissue(red marrow) decreases and is replaced by fat (yellow marrow).

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6
Q

What is the difference between bone marrow trephine and marrow aspirate?

A

BONE MARROW TREPHINE – Trephine biopsy used to examine bone marrow architecture

BONE MARROW ASPIRATE – Used to examine cellular morphology

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7
Q

describe pluripotent stem cells(4)

A

 Unlimited self-renewal-

  1. Pluripotent stem cells can give rise to all cell types of the body (but not the placenta).
  2. Present in marrow in small numbers and they have a
  3. High resistance to chemotherapy- they are not affected through the therapy
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8
Q

What can dysfunction of pluripotent cells lead to?(2)

A

Aplastic Anaemia or certain leukaemia- cells cannot perforate.

  1. Chronic myeloid leukaemia (CML) is caused by a chromosome translocation in a stem cell
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9
Q

Describe multipotent stem cells (4)

A

 Derived from Pluripotential Stem Cells
 Capable of extended Self Renewal
 Capable of extended Differentiation.

  1. Lymphoid and Myeloid stem cells
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10
Q

Compare lymphoid and myeloid stem cells

A

 Lymphoid stem cells give rise to mature lymphocytes- T and B lymphocytes.
 Myeloid stem cells give rise to red cell, granulocytes(neutrophils) and platelets.
 Lymphoid stem cells can also give rise to lymphoproliferative malignancies;
 Myeloid stem cells can also give rise to myeloproliferative leukaemia

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11
Q

What are progenitors?

A

Progenitors are unipotent, and in some cases oligopotent, differentiating into only one or a few cell types.

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12
Q

Describe progenitors(5)

A

 Derived from multipotent stem cells
 Capable of limited self-renewal
 Capable of limited differentiation. Different forms, granulocytes, erythrocytes, etc.
 Responsive to heamatopoietic GFs; e.g. EPO stimulates CFU-E
 Express differentiation surface antigens; e.g. CD71 on erythroid PC.

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13
Q

How can progenitors be detected?

A

by special in vitro assays where colonies are formed, (e.g. CFU)

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14
Q

What are precursor cells?

A

Blasts and their progeny

  1. First morphologically identifiable cells
  2.  Little if any self-renewal
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15
Q

What is erythropoiesis?

A

the process of erythrocyte generation, which occurs in the bone marrow and is dependent on EPO release from the kidneys as described above

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16
Q

Describe the steps of erythropoeisis

A

→ PROERYTHROBLAST-
a large nucleus-containing cell with no hemoglobin and prominent organelles.
→ • As this cell differentiates, its size becomes progressively smaller, organelles are lost, and its color changes from blue- BASOPHILIC ERYTHROBLAST
→ POLYCHROMATIC ERYTHROBLAST
→ PYKNOTIC ERYTHROBLAST- are slightly larger than mature red blood cells. They have small, round nuclei and dense, pyknotic chromatin
→• The cells which exit the bone marrow and into the circulation are not fully mature and still contain a small amount of nucleotide content that renders them slightly basophilic- RETICULOCYTE
→MATURE RED BLOOD CELL
As we go along, the nucleus shrinks and the cytoplasm gets pinker

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17
Q

How is erythropoiesis regulated? (2)

A

by erythropoietin, a soluble protein synthesized by the kidneys in response to low arterial oxygen tension within the blood.
2. when the blood’s oxygen tension is low, increased eyrthropoietin levels stimulate enhanced erythropoiesis which boosts the levels of erythrocytes in the blood

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18
Q

What is granulopoiesis?(2)

A

refers to the process by which mature granulocytes differentiate within the bone marrow.
2. The earliest stage cell which appears to be committed to the granulocyte lineage is the large rapidly dividing “Myeloblast”

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19
Q

What are the precursors for granulopoeisis?

A

Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band

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20
Q

Describe platelet formation

A

→ MEGAKARYOBLAST (to the next step, there is only DNA replication, no cell division)
→MEGAKARYOCYTE- long-lived cells that continuously produce platelets
→ BLOOD PLATELETS

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21
Q

What diseases are related to low platelet levels?

A

idiopathic thrombocytopaenic purpura

2. and predispose to bleeding

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22
Q

Describe the steps of myelpoiesis

A 
→myeloblast
→ promyelocyte
→ myelocite
→metamyelocyte
→ band
→ segmented neutrophil (Caps ones are more important)
23
Q

What happens to granules as neutrophils mature?(3)

A
  1. Primary (azurophilic) granules develop as neutrophils are differentiating from myeloblasts to promyelocytes.
  2. Secondary (specific) granules form in myelocytes and metamyelocytes.
  3. Tertiary (gelatinase) granules first appear in band cells.
24
Q

Describe lymphopoiesis

A

Antigen independent phase:
 Initial lymphopoiesis in bone marrow
 Maturation occurring in lymph nodes & thymus
 Antigen dependent phase
2nd cycle of differentiation & proliferation in response to antigen exposure
 Memory phase
 Follows antigen exposure

25
Q

Describe T-cell formation (3)

A

 Early progenitor migrates to thymus
 T-cell receptor gene rearrangement
 positive to check that they work & negative selection

26
Q

Describe B- cell formation(4)

A

→B-Cell formation occurs in the bone marrow.

→Immunoglobin gene arrangement occurs.

→expression of surface IgM (immunoglobulin)

→The immature B-Cell migrates to the secondary lymphoid organs (lymph nodes) for maturation and antigen selection.

27
Q

What regulates haematopoiesis?

A

dependent on glycoprotein growth factors, which drive the proliferation and differentiation of progenitor cells. Examples include: EPO, CSF

28
Q

How do CSFs stimulate growth?(4)

A

 HSC are brought in contact with stromal cells
 There is cell-cell communication by binding via cell surface transmembrane receptors to secreted cytokines or GF.
 Stimulate growth and survival of progenitors.
 Binding triggers signal transduction, followed by gene transcription, proliferation, differentiation and apoptosis

29
Q

Recall some growth factors

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

30
Q

What is erythropoietin?(2)

A

Its release is triggered by low haemoglobin concentration.

The gene for EPO is located on chromosome 7 and the product is a 165 amino acid polypeptide hormone

31
Q

How does erthropoeitin increase red blood cell?

A

by increasing survival of erythroid progenitors (CFU-E)

32
Q

Describe erythropoietin(3)

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) and Acts on late progenitors

33
Q

What are some clinical applications of erythropoietin?

A

 Treating anaemia of kidney failure

 Alternative to blood transfusion in Jehovah’s Witnesses

34
Q

Describe Granulocyte Colony Stimulating Factor

A

 Produced by many cell types, In response to inflammation

 Acts on mature neutrophils in the periphery

35
Q

What is the role of Granulocyte Colony Stimulating Factor?(5)

A

 Chemoattractant

 promotes neutrophil maturation

 promotes neutrophil activation

 Stimulates neutrophil production in the bone marrow
stimulates neutrophil progenitors (CFU-G)

  1. helps stimulate progenitors of other lineages, but only in combination with other growth factors.
36
Q

What are some clinical applications of G-CSF?(3)

A

 treatment of hereditary neutropenia and other causes of neutropenia
 stimulate neutrophil recovery after chemotherapy and bone marrow transplantation; as well as other lineages
 G-CSF treatment causes stem cells to be released from the bone marrow into the circulation

37
Q

What type of cells can be used in bone marrow transplantation?

A

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

38
Q

What are some clinical applications of bone marrow transplantations?

A

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

39
Q

What are some risks to bone marrow transplantations?

A

Significant mortality while waiting for engraftment
o Infection due to neutropenia (low neutrophil count)
o Bleeding due to thrombocytopenia (low platelets)
o Graft versus Host Disease (GVHD)

40
Q

what do high level of reticulocytes in the blood mean?

A

→ that the bone marrow is working overtime to produce new red cells

41
Q

why are progenitors considered undifferentiated?

A

→undifferentiated because you cannot tell the difference between them morphologically
since they don’t show the characteristics of mature cells.

42
Q

why are progenitors considered committed?

A

→they are committed to what they will become when they produce mature cells

43
Q

Why are progenitors called Colony Forming Units (CFUs) and how many cells can be in a colony?

A

→Progenitors grow to form colonies of mature cells.

→ from 32 to hundreds or thousands of cells in a colony.

44
Q

what are some examples of some colony forming units?

A 
CFU- G granulocyte progenitor
→ CFU- GM granulocyte/monocyte progenitor
→ CFU - E erythroid progenitor
→ CFU- bas
→ CFU-eo
→ CFU - MK megakaryocyte progenitor
45
Q

why do some erythroid colonies look like they have burst and what are they called?

A

→ because they are mobile

→ BFU - E (burst forming unit)

46
Q

what is G-CSF used for?

A

→ used for patients that are not making neutrophils due to chemotherapy

47
Q

what are the steps for bone marrow transplantation?

A

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

48
Q

How did we prove that haematopoietic stem cells are pluripotent?

A

→ proved via mice.
→Stem cells were marked by retrovirus insertion.
→then transplanted into irradiated mice with a small number of stem cells.
→The same marked stem cells gave rise to neutrophils, lymphocytes, etc.

49
Q

Describe chronic myeloid leukaemia (CML)

A

→Chronic Myeloid Leukaemia (CML) is caused by a chromosome translocation in a stem cell. 9 and 22

→excess production of neutrophils and neutrophil precursors

→CML mostly affects neutrophil lineage, but the Philadelphia chromosome is also found in T-lymphocytes and other lineages.

50
Q

What cells present the CD34 antigen, and why?

A

→Stem cells and early progenitors carry the cell surface antigen CD34.

→ used to purify stem and progenitor cells.

51
Q

How does G-CSF treatment contribute to Peripheral Blood Stem Cell Transplantation (PBSCT) and how is PBSCT used?

A

→G-CSF treatment causes stem cells to be released from the bone marrow into the circulation.

→This is seen by the appearance of CD34 on cells in the circulation.

→We can collect the stem cells by leukapheresis.

52
Q

What is reticulocyte?

A

→Immature RBC that just left the bone marrow.

→Still has some RNA, ribosomes.

→Quickly loses these to make a mature RBC.

53
Q

why can PBSCT be used as an alternative to bone marrow for transplantation?

A

It’s less traumatic for the donor, as it is so painless that it does not require a general anaesthetic.

Year One: Pesky Things (20 decks)

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