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ESA 2 - MEH > 5. Haemopoiesis > Flashcards

5. Haemopoiesis Flashcards

1
Q

What is haemopoiesis?

A

Process by which blood cells (RBCs, WBCs and platelets) are formed from haemopoietic stem cells. Involves:

  • specification of blood cell lineages
  • proliferation to maintain an adequate no. of cells in circulation
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2
Q

Where does haemopoiesis occur in the embryo and after birth? What is the distribution of this tissue?

A
  • In early embryo process begins in vasculature of yolk sac before shifting to embryonic liver by week ~5-8 gestation.
  • Shortly after birth, sole site of haematopoiesis = bone marrow.
  • BM extensive through skeleton in infant, more limited distribution in adulthood: pelvis, sternum, skull, ribs and vertebrae (axial skeleton).
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3
Q

How is haematopoiesis examined clinically?

A
  1. Bone marrow trephine biopsy from upper iliac crest of pelvis
  2. Spread of cells from bone marrow aspirate
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4
Q

What are the 5 major lineage pathways to arise from HSCs?

A
  1. thrombopoiesis (platelets)
  2. granulopoiesis (basophils, neutrophils and eosinophils)
  3. erythropoiesis (erythrocytes)
  4. monocytopoiesis (monocytes)
  5. lymphopoiesis (B and T lymphocytes)
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5
Q

Which 2 cell types do MHCs give rise to?

A

Common lymphoid progenitor and common myeloid progenitor.

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6
Q

Which cell types does the common myeloid progenitor give rise to?

A
  1. megakaryocytes
  2. erythrocytes
  3. myeloblasts
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7
Q

What are platelets and how are they formed?

A

Thrombocytes = membrane bound fragments of cytoplasm that but off from megakaryocytes - have no nuclei.
Involved in clot formation.

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8
Q

What are megakaryocytes?

A

very large mononucleated cells with several copies of each pair of chromosomes (i.e. polyploid cells)

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9
Q

Which hormones stimulate thrombopoiesis?

A
  • thrombopoietin (TPO)

- (GM-CSF)

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10
Q

What is granulopoiesis?

A

Production of granulocytes (neutrophils, basophils and eosinophils) from myeloblast cells.

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11
Q

Which hormones stimulate granulopoiesis?

A
  • granulocyte colony-stimulating factor (G-CSF)

- granulocyte-macrophage colony-stimulating factor (GM-CSF)

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12
Q

What is the function of basophils and eosinophils? What is their inappropriate activation associated with?

A

Phagocytosis, associated will immune response to multicellular parasites.
Basophils are least common of granulocytes.

Asthma and allergy

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13
Q

Which hormones stimulate monocytopoiesis?

A

GM-CSF

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14
Q

Which cell types does the common lymphoid progenitor give rise to?

A
  • B lymphocytes
  • T lymphocytes
  • NK cells
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15
Q

Which hormones stimulate lymphopoiesis?

A

ILs and TNFs

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16
Q

Describe the production of B and T cells.

A
  • B cell dev starts in foetal liver and BM - during dev, Ig genes rearrange to allow production of antibodies with a wide array of specificities.
  • Final B cell maturation requires exposure to antigen in lymph nodes. Results in mature B cells with capacity to recognise non-self antigen and produce large quantities of specific antibodies,
  • T cell progenitors however arise from foetal liver and migrate to thymus early in gestation.
  • Immature T cells undergo rearrangement of the TCR genes - ability to produce vast array of different TCRs which can recognise wide range of antigens presented to them by APCs.
17
Q

Why does erythropoiesis need to be a continual process?

A

RBCs lack ability to divide and have finite lifespan of ~120 days

18
Q

Which factors promote erythropoiesis? How does this work?

A
  • Expression of transcription factors GATA1, FOG1 and PU.1 commits progenitor cells in the BM to the erythroid lineage.
  • Once committed, further expansion of erythroid precursors is largely driven by erythropoietin released from kidneys.
19
Q

What stimulates EPO production by the kidneys?

A

increases in response to a decrease in O2 levels in bloodstream - hypoxia

20
Q

Describe the process of erythropoiesis.

A
  1. EPO = glycoprotein hormone that function to inhibit apoptosis of CFU-E (colony-forming units of erythroid cell line) progenitor cells. Activation of EPO Rs on these cells allows them to develop, proliferate and differentiate.
  2. During process, nucleated erythroblasts extrude their nucleus and most of their organelles to form reticulocytes (immature RBCs) which are released into circulation.
  3. In blood, extrude remnants of organelles such as MT and ribosomes and take ~1-2 days to mature into RBCs.
21
Q

What is a good diagnostic estimate of the amount of erythropoiesis occurring in BM?

A

reticulocyte count from blood sample

22
Q

Why are RBCs particularly susceptible to metabolic diseases?

A
  1. Lack nuclei so are unable to replace damaged proteins by re-synthesis - particularly susceptible to oxidative damage in diseases such as glucose-6-phosphate dehydrogenase deficiency.
  2. Lack of MT and reliance on glycolysis for energy production makes biochemical consequences of pyruvate kinase deficiency particularly relevant to RBCs.
23
Q

By which system are old/damaged RBCs removed?

A

reticuloendothelial system

24
Q

What is the reticuloendothelial system and what is its role?

A
  • Network of phagocytic cells located throughout the body, part of the larger immune system.
  • Cells remove abnormal, old or dead cells, foreign matter and foreign organisms.
25
Q

Give examples of cells in the RES and their location.

A 
1- kupffer cell (liver)
2- tissue histiocyte (CT)
3- microglia (CNS)
4- peritoneal macrophage (peritoneal cavity)
5- red pulp macrophage (spleen)
6- langerhans cell (skin and mucosa)
26
Q

Which organ has a particularly predominant role in the RES? What happens to patients without this organ?

A

Spleen

  • filters all blood to remove deformed and old cells from circulation.
  • holds a small reserve of blood which can be released in haemorrhagic shock and acts as platelet reservoir.

Can survive without spleen (e.g. surgical removal after accidental rupture due to trauma or to treat diseases such as hereditary spherocytosis). Increased risk of sepsis and Ps usually given various vaccinations to compensate for inadequate opsonisation of bacteria.

27
Q

Describe the breakdown and recycling of erythrocytes.

A
  1. Haemoglobin removed from senescent RBCs is recycled by spleen with globin portion degraded to constitutive aa and haem portion metabolised to bilirubin.
  2. Bilirubin removed in liver where it is conjugated and secreted in bile.
  3. Bacteria in colon deconjugate and metabolise bilirubin into colourless urobilinogen which is subsequently oxidised to form urobilin and stercobilin (responsible for brown colour of stool).
  4. Small amount of urobilinogen is reabsorbed and processed by kidneys, giving urine its yellow colour.

ESA 2 - MEH (42 decks)

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