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Year 3 Clinical > Haemopoiesis > Flashcards

Haemopoiesis Flashcards

1
Q

Define haemopoiesis?

A

Formation of blood cells

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2
Q

Function of red cells?

A

Erythrocytes (no nucleus) - O2 / CO2 transport

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3
Q

Function of platelets?

A

No nucleus

Primary haemostasis

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4
Q

Functions of white cells?

A

Granulocytes:
• Neutrophils - phagocytosis and mediate acute inflammation
• Eosinophils - destroy parasites and modulate hypersensitivity reactions
• Basophils - modulate hypersensitivity reactions

Monocytes (differentiate into macrophages):
• Modulate immune reactions
• Phagocytic clearance
• Regulatory functions

Lymphocytes:
• B cells - humoral immunity (antibodies)
• T cells - cell-mediated immunity and regulatory functions
• Natural Killer (NK) cells - anti-viral / tumour

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5
Q

Various processes by which the blood cells are formed?

A

Haemopoiesis - production of blood cells; umbrella term for the rest

Erythropoiesis

Thrombopoiesis

Myelopoiesis or granulopoiesis

Lymphopoiesis

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6
Q

Level of productivity of red cells?

A

x 10(12) /L - red cells are the most abundant blood cell

Lifespan is ~120 days

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7
Q

Level of productivity of neutrophils?

A

x 10(9) /L

Lifespan is ~7-8 hours

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8
Q

Level of productivity of platelets?

A

x 10(9) /L

Lifespan if ~7-10 days

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9
Q

Ancestry of rbcs?

A
  1. Pronormoblast
  2. Early normoblast
  3. Intermediate normoblast
  4. Late normoblast
  5. Reticulocyte - immediate red cell precursors that cause polychromasia; they lose their RNA over 1-7 days
  6. Mature rbc
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10
Q

How do platelets form?

A

Cytoplasmic fragments of megakaryocytes

NOTE - megakaryocytes are polypoid cells that are platelet precursors

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11
Q

What are ‘blast’ cells?

A

Nucleated precursor cell:
• Erythroblast - rbc precursor
• Myeloblast - neutrophil lineage

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12
Q

What are myelocytes?

A

Nucleated precursor between neutrophils and blasts

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13
Q

Ancestry of blood cells, i.e: precursors of the precursors?

A

Haemopoietic progenitor cell; progenitors and, ultimately, all haemopoietic cells come from haemopoietic stem cells

All of the haemopoietic stem progenitor cells look the same and, on microscopy, cannot differentiate those that will give rise to one type of cell from another

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14
Q

Properties of the pluripotent stem cells?

A

Self-renewal - a property of stem cells that is lost in its descendants

Proliferation - increase in numbers

Differentiation - the descendants go through lineage-commitment, where they choose a certain lineage:
• Myeloid (granulocytes, monocytes, megakaryocytes, and dendritic cells)
• Lymphoid (T cells, B cells, NK cells)

Maturation - descendants acquire functional properties and may stop proliferation; e.g: reticulocytes, mature rbcs, neutrophils cannot proliferate

Apoptosis - descendants undergo cell death

NOTE - there is an overlap between developmental event, e.g: proliferation and maturation can occur simultaneously

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15
Q

Define myeloid?

A

May refer to bone marrow, e.g: myeloid/marrow malignancy

May refer to lineage, e.g: non-lymphoid

Granulocytes and precursors - myeloid : erythroid ratio

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16
Q

Sites from which haemopoietic stem cells are derived?

A

From the mesoderm

Circulating committed progenitors are detectable as early as week 5

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17
Q

Sites of haemopoiesis throughout life?

A

Yolk sac - 1st site of erythroid activity; stops by week 10

Liver - starts by week 6

Spleen - starts by week 12; it likely only contributes a small amount in humans

Bone marrow - starts by week 16 and continues throughout life

18
Q

Location of bone marrow in adults?

A

Mainly the axial skeleton but also the proximal ends of long bones, e.g: humerus and femur

19
Q

Where are bone marrow biopsies taken from?

A

In adults, from the posterior iliac crest

In children,

NOTE - specific injections are administered in order to mobilise stem cells from the bone marrow into the blood, for collection and transplantation

20
Q

Structure of bone marrow?

A

Complex organ surrounded by a shell of bone, with a neurovascular supply

Trabecular bone projects into the bone marrow and this form the endosteum, which is the interface between bone and bone marrow

21
Q

Compartments in the bone marrow?

A

Cellular:
• Haemopoietic cells
• Non-haemopoietic cells, e.g: adipocytes, fibroblasts, osteoclasts, osteoblasts

Connective tissue matrix

Vascular elements

22
Q

Describe bone marrow vasculature

A

Supplied by a nutrient artery and a periosteal network’ arterioles drain into sinuses; these venous sinuses drain into larger central sinuses

NOTE - compared to capillaries, sinuses are larger and have a discontinuous basement membrane, with open pores, increasing the permeability

23
Q

Structure of the bone marrow sinus walls?

A

Endothelial cells have gaps between then called fenestrations

At some regions, the endothelial cells form tight junctions, for tighter control of entry/exit into the sinus

Adventitial cells can contract to change become smaller

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24
Q

How are mature blood cell released from marrow?

A

Can pass through fenestrations in endothelial cells, to enter the circulation

25
Q

Changes that occur due to the release of red cells?

A

Assoc. with sinusoidal dilatation and increased blood flow

26
Q

Where do neutrophils go once released from the marrow?

A

Actively migrate towards the sinusoid

27
Q

What do megakaryocytes do once released?

A

Extend long branching processes, called proplatelets, into the sinusoidal blood vessels

28
Q

Difference between red and yellow marrow?

A

Red marrow - haemopoietically active

Yellow marrow - fatty, inactive marrow; increases with age and this results in reduced marrow cellularity in older individuals

29
Q

Calculating cellularity?

A

100 - age = cellularity (%)

30
Q

What is the myeloid : erythroid ratio?

A

Relationship of neutrophils and precursors to proportion of nucleated red cell precursors

31
Q

Normal myeloid : erythroid ratio?

A

Ranges from 1.5 : 1 to 3.3 : 1

This can change, e.g: reversal in haemolysis as a compensatory response

32
Q

Regulation of haemopoiesis?

A
  1. Intrinsic properties of cells, e.g: stem cells vs progenitor cells vs mature cells; different cells have different transcription factors
  2. Signals from immediate surroundings and the periphery, i.e: microenvironmental factors
33
Q

Examples of regulation of haemopoiesis?

A

Erythroid maturation occurs around ‘nurse’ macrophages in the form of islands

Neutrophil and its precursor maturation is regulated by G-CSF (granulocyte-colony stimulating factor)

Thrombopoietin regulates growth and development of megakaryocytes from their precursors

34
Q

Microenvironmental regulation of haemopoiesis (for stem cells)?

A

Haemopoietic stem cells occupy a niche (anatomical site) that provides signals for expansion, differentiation or dormancy

These niche areas are around vasculature (arteriole or sinusoid) and provide access to cytokines

NOTE - the niche can be altered in disease states or with therapy

35
Q

Investigations used to assess haemopoiesis?

A

Routinely undertaken:
• Blood count
• Cell indices
• Morphology (blood film)

Less common (specialist tests):
• Bone marrow examination
36
Q

Appearance of blood cells on blood film?

A

i.e: ID cells using their morphology

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NOTE - monocytes and lymphocytes are mononucleocytes, i.e: they do not have segmented nucleus

37
Q

Investigating mature cells?

A

Blood count and morphological assessment are often sufficient

Expression of antigens indicating the lineage or stage of development can be studied but not usually required

Study of antigen expression using specific antibodies (immunophenotyping)

38
Q

How do we assess haemopoiesis?

A

Haemopoietic progenitor/stem cells are morphologically indistinguishable from one another

  1. Immunophenotyping
  2. Cytochemistry
  3. Clonogenic assays
  4. Animal models
39
Q

What is immunophenotyping?

A

Identifies pattern of antigen expression unique to a cell lineage; it uses combinations of antibodies that are specific to different antigens

40
Q

Process of immunophenotyping?

A

Antibodies are used to target various antigens on cells; these antibodies have fluorochrome on them, which emits lights of different colours when hit with a laser
Software (flow-cytometry) then detects the colour of light emitted

E.g: when a specific antibody binds to CD3 on T-lymphocytes, green light is emitted
When a specific antibody binds to CD34 on haemopoietic stem cells, red light is emitted

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Year 3 Clinical (100 decks)

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