Haematology (Haemopoiesis and the bone marrow) Flashcards

1
Q

How many blood cells are produced in the bone marrow each day in healthy individuals?

A

5-10 x 10^11

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2
Q

Where does haemopoiesis commonly occur? What other places can it occur in?

A

In the bone marrow

  • In certain pathological conditions it can occur in tissue (liver, lymph nodes, spleen)
  • In neonates can occur in the embryonic yolk sac
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3
Q

How long after gestation does the bone marrow take over haemopoiesis?

A

5-9 months

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4
Q

In infacts, what bones does haemopoiesis occur in?

A
  • Axial skeleton

- Proximal ends of long bones e.g femur

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5
Q

In adults, what bones are the locations for haemopoiesis?

A
  • Sternum and iliac crests

- Skull, vertebrae and ribs may be involved

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6
Q

What are the 3 main structures of the bone marrow? Briefly describe each

A

1) Haemopoietic cells
- sometimes known as cords

2) Sinuses
- consist of vascular spaces that are lined with endothelial cells to regulate the release of mature blood cells

3) Non-haemopoietic cells
- Tissues that:
> support the bone marrow structure e.g stromal cells such as fibroblasts
> Produce growth factors e.g macrophages
> Store fat e.g adipocytes

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7
Q

What are pluripotent stem cells and what do they become?

A

A common primitive stem cell in the bone marrow

- can differentiate into lineage-specific stem cells e.g the common myeloid and common lymphoid progenitors

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8
Q

How easy is it to differentiate pluripotent stem cells from mature cells?

A

Almost impossible

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9
Q

How can linage-specific stem cells be differentiated from mature cells?

A

Presence of surface markers such as CD34

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10
Q

What are stem cells sometimes known as?

A

Colony forming units

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11
Q

Regulation of haemopoiesis is controlled by what?

A

Colony-stimulating factors (CSFs)

- function like cytokines

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12
Q

How does granulocyte-macrophage CSF (GM-CSF) work?

A

Can non-specifically stimulate the differentiation of all blood cells

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13
Q

Give some examples of growth factors that are lineage specific

A
  • Erythropoietin (EPO) - red blood cell lineage

- Thrombopoietin (TPO) - platelet lineage

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14
Q

Describe the process of erythropoiesis

A

1) Pathway starts with common myeloid precursor CFU-GEMM
2) CFU-GEMM gives rise to the megakaryocytic precursor (CFU-Emk)
3) CFU-Emk produces the red cell lineage-specific stem cell CFU-E
4) CFU-E develops into the proerythroblast and divisions reduce its size to a nucleated RBC
5) Loss of nucleus results in generation of a juvenile RBC known as a reticulocyte
6) Maturation occurs over 3-4 days to mature RBC

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15
Q

What immune cells are the granulocytes?

A

Neutrophils, eosinophils and basophils

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16
Q

Describe the process of granulopoiesis

A

CFU-GEMM develops into 4 CFUs:

  • CFU-baso
  • CFU-neut
  • CFU-eos
  • CFU-M (monocyte precursor)
17
Q

At what stage can lineage-specific precursors of mature granulocytes be recognised?

A

The myelocyte stage

18
Q

How can these myelocyte stage granulocyte precursors be recognised?

A

Staining of their granules

19
Q

What enzymes and molecules can be found within the granules?

A
  • myeloperoxidase
  • collagenase
  • heparin
  • lactoferrin
  • histamine
20
Q

Describe the process of thrombopoiesis

A
  • Lineage-specific progenitor cell CFU-MK develops into the megakaryoblast and then onto the megakaryocyte
  • Megakaryocytes produce pseudopodial projections of the cytoplasm called proplatelets across the endothelial layer of blood vessels
  • The force of the blood cause proplatelets to break off into circulation
  • Proplatelets differentiate into platelets by twisting and pinching as midline
21
Q

What are the typical serum levels of platelets? What can affect this number?

A

100 pg/L

- can increase in throbocytopenia, aplastic anemia and in acute inflammation

22
Q

How many platelets are produced each day?

A

10^11

23
Q

What occurs are production of 1,500-4,000 platelets from one megakarocyte?

A

Nothing remains but the nucleus

- phagocytosed by bone marrow macrophages

24
Q

Describe the production of monocytes

A
  • Common precursor with granulocytes (CFU-Gmo)
  • Becomes 2 species of immature monocyte:
  • monoblast
  • promonocyte
  • Promonocytes develop into mature monocytes that enter blood
25
Q

What happens to monocytes after a few days in circulation?

A

Become macrophages

26
Q

What are some specialized APCs that some macrophages develop into

A

1) Langerhans cells (spleen)
2) Kupffer cells (liver)
3) Interdigitating dendritic cells (all tissues)

27
Q

Describe the production of lymphocytes

A
  • Common lymphoid progenitor (CFU-L) gives rise to immature lymphoblasts which deifferentiate into mature lymphocytes; B cells, T cells and NK cells
28
Q

What is the M/E ratio? What should it be in healthy adults?

A

Ratio of myeloid (M) precursors to erythroid (E) precursors

approx 3-4:1 in healthy adults

29
Q

Name some diseases associated with an increased or reduced M/E ratio

A

Increased

  • Myeloid leukaemia
  • Most infections

Reduced:

  • Suppressed myelopoiesis e.g chemo, viral infection
  • Enhanced erythopoiesis
    e. g blood loss, iron deficiency
30
Q

What is cytochemistry and what is it primarily used for?

A
  • Exploits the way that components of the cytoplasm react with dyes (e.g granules)
  • Used to detemine identity and number of WBCs and their precursors
31
Q

What is flow cytometry primarily used for?

A

Used to assess cell populations based on molecules on the cell surface
- Uses monoclonal antibodies conjugated to a fluorochrome to defined cell surface antigens e.g CD34

32
Q

Name some CDs that can be found on B cells, T cells, myeloid cells, monocytes, haemopoietic precursors and WBCs

A
T: CD2, CD3
B: CD10, CD20
Myeloid: CD13, CD33
Monocytes: CD14
Stem cells: CD34
WBCs: CD45