Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

LF266: Blood and Circulation > Lecture 5: Haematopoesis > Flashcards

Lecture 5: Haematopoesis Flashcards

1
Q

What is hematopoiesis?

A
  • Highly organized differentiation process
  • Ordered expression of different sets of genes
  • Controlled by factors in the environment of the developing blood cell — the bone marrow in adults
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How many blood cells do we make daily?

A
  • We make 5x10^11 blood cells daily
  • Mature blood cells in healthy individuals mostly hv short life times (exception: lymphocytes) n are constantly regenerated in the bone marrow
  • This is accelerated when there is hematological stress, such as
    • Infection, need more leukocytes
    • High altitude, need more RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

When does haematopoiesis begin?

A

3w after conception

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How does the location of blood cell production change during embryonic development?

A

First stage of blood cell production happen in the yolk sac then switches to the liver then the bone marrow when you start making bones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the two sets into which the embryo separates during early development, and what role do they play in hematopoiesis?

A

During early development, the embryo separates into two sets:

  1. One set generates the embryo proper and all the tissues of the adult.
  2. The other set forms the yolk sac, where mesoderm is located, serving as the initial site for the formation of blood cells and blood vessels.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

When does the liver start producing blood cells in human development, and what significance does this hold?

A

The liver starts producing blood cells around eight weeks into development. This transition marks an important genetic switch in hematopoiesis, signifying the shift of blood cell production from the yolk sac to the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are hemangioblasts, and what role do they play in embryonic hematopoiesis?

A
  • Hemangioblasts are mesoderm-derived cells that differentiate to form nucleated RBCs and endothelial cells, which generate a capillary system (plexus) within the yolk sac
  • At the same time the heart and aorta start to form - join up with the capillary plexus and the erythrocytes start to circulate
  • Contribute to the formation of the capillary system (plexus) within the yolk sac during embryonic hematopoiesis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the transition of hematopoiesis during embryonic development.

A
  • Initially, hematopoiesis occurs in the yolk sac, where hemangioblasts differentiate to form blood cells and endothelial cells.
  • As embryogenesis progresses, hematopoiesis shifts primarily to the liver, and at birth, it transitions to the bone marrow.
  • This definitive hematopoiesis in the bone marrow allows for the production of the entire range of blood cells found in adults.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is definitive erythropoiesis?

A
  • The later stage of embryogenetic haematopoiesis (before its ‘primitive erythropoiesis’ in the yolk sac)
  • Occurs mainly in the liver and at birth switches to the bone marrow
  • Produces entire range of blood cells you would find in an adult
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the significance of the hematopoietic niche?

A

The hematopoietic niche is where stem cells develop and divide. It consists of cells derived from the bone marrow, including stromal cells, osteoblasts, and osteoclasts.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do osteoblasts and osteoclasts contribute to the hematopoietic niche?

A
  • Osteoblasts: bone formation
  • Osteoclasts: bone resorption or dissolution
  • Continual balance between these two cell types is crucial for maintaining the bone marrow environment and regulating hematopoiesis.
  • This balance can be influenced by hormones and age.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is definitive erythropoiesis?

A
  • The later stage of embryogenetic haematopoiesis (before its ‘primitive erythropoiesis’ in the yolk sac
  • Occurs mainly in the liver and at birth switches to the bone marrow
  • Produces entire range of blood cells you would find in an adult
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Where does hematopoiesis occur in the body?

A

Bones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What additional function do bones serve besides supporting the body’s structure?

A

Reservoir for calcium and phosphate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the range of cells found in the bone marrow highly specialised tissues?

A
  • Haematopoietic cells
  • Stromal cells → provides support functions for haematopoietic cells
  • Osteoblasts n osteoclasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How does the distribution of hematopoiesis change as a person ages?

A

As a person ages, not all bones continue to produce blood, and different bones take on different roles in hematopoiesis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What can happen when the regulation of hematopoiesis goes awry, as seen in myeloma?

A

In myeloma, aberrant hematopoiesis can occur, leading to the production of red blood cells in the wrong cells and the emergence of antibody-producing clones → loss of regulation in blood cell production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the composition of cortical bone?

A

70% hydroxyapatite in a rigid outer layer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the inner core of bone called, and what are its characteristics?

A
  • Cancellous or trabecular bone
  • Less dense and spongy in nature.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the significance of the epiphysis in bone structure?

A

The epiphysis serves as a niche where stem cells are typically found, and its soft and spongy nature allows for the presence of holes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the medullary cavity, and why is it important?

A

Cavity in the epiphysis where red blood cell production occurs and is subsequently halted, as it is a site where new bone cells cannot be generated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the role of the endosteum in bone structure?

A
  • The endosteum is the inner layer of spongy bone
  • Serves as sites for bone marrow niches.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are osteons, and what is their structure?

A
  • Circular structures observed when cutting through bones.
  • Consist of Haversian canals that run longitudinally and Volkmann canals that traverse across the bone.
    • These canals provide passages for blood vessels.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the function of the canals within bones?

A

Pathways for blood vessels, allowing for the transportation of nutrients, oxygen, and newly produced blood cells within the bone tissue.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What occurs within the porous bones in terms of blood cell production?

A
  • Within the porous bones, islets are formed where processes like the sloughing of megakaryocytes and pooling of red blood cells take place
  • Facilitates the release and circulation of newly formed blood cells.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are the two types of bone marrow, and where are they primarily found?

A
  • Red bone marrow is primarily found in flat bones and the epiphyses of long bones, such as in the pelvis, sternum, and ribs, where it is involved in the production of RBCs
  • Yellow bone marrow is found in the shafts of long bones.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How does the composition of red bone marrow differ from yellow bone marrow?

A
  • Red bone marrow is intensely cellular and contains a high proportion of hematopoietic (blood-forming) cells, particularly involved in RBC production.
  • Yellow bone marrow contains a significant amount of adipose (fat) tissue, especially in older individuals, and has a reduced capacity for blood cell production.
28
Q

What is a hematopoietic stem cell (HSC), and how was its role in blood production understood?

A
  • The understanding of the hematopoietic role of bone marrow (BM) began developing in the 1960s with research on the effects of radiation in animals. I
  • t was observed that the main cause of death after exposure to ionizing radiation is hematological failure.
    • While blood transfusion or most lymphoid tissues did not save the animals, BM transfusion did.
29
Q

What are some characteristics of hematopoietic stem cells (HSCs) regarding self-renewal and limitations?

A
  • HSCs are capable of self-renewal, although not indefinitely
  • Repeated serial transplants have been performed, indicating their ability to sustain blood cell production over multiple transfers.
  • However, these cells are not immortal, as evidenced by the eventual failure of transplants.
  • This limitation is linked to the Hayflick limit, associated with the end replication problem and telomere shortening.
  • Chromosomes in stem cells experience telomere shortening
30
Q

What is the role of HSCs in blood cell production?

A

Multipotent parental cell type for all blood cells, including red blood cells, white blood cells, and likely endothelial cells.

31
Q

What theory proposes the function of HSCs in blood cell production?

A

There is a single HSC responsible for producing all types of blood cells, implying that each HSC generates only one type of cell.

32
Q

How were the experiments demonstrating multipotency of hematopoietic stem cells conducted?

A

The experiments relied on irradiating bone marrow cells with small doses of radiation, which caused minor chromosome alterations in rare cells without killing them.

33
Q

What happens when cells are exposed to ionizing radiation?

A
  • Ionizing radiation causes double-strand breaks in DNA, prompting repair processes in the cells to mend the breaks.
  • The resolution of this repair involves mixing and matching genetic material, leading to distinctive cells with unique markers.
34
Q

How do clonal cells behave in relation to chromosomal rearrangements?

A

Clonal cells, derived from a single cell with unique markers, exhibit the same pattern of chromosomal rearrangement as they divide, resulting in a lineage of cells that are both unique and clonal.

35
Q

What did the experiments reveal about the distribution of unique rearrangements in hematopoietic stem cells?

A

Unique rearrangements made in the hematopoietic stem cells were found to be present in every cell in the bone marrow, indicating that a single cell carried a marker for these rearrangements.

36
Q

How did the experiments demonstrate the presence of a stem cell driving different lineages?

A

Some cells showed rearrangements specific to lymphoid tissues, such as B or T cells, suggesting the presence of a stem cell driving these lineages exclusively.

37
Q

What were the observations regarding the distribution of markers in different leukocyte types?

A

In some transplanted mice, all leukocyte types bore the same marker, indicating a myeloid lineage origin, while in others, only myeloid or lymphoid cells showed the same marker, suggesting lineage-specific markers for these cell types.

38
Q

What is the implication of the experiments regarding the potency of stem cells?

A
  • Presence of stem cells with more restricted potency, capable of producing either myeloid or lymphoid cells.
  • These cells are now known as common lymphoid progenitor (CLP) and common myeloid progenitor (CMP) cells.
39
Q

How are CLP and CMP cells characterized?

A
  • CLP cells → lymphocytes
  • CMP cells → granulocytes, erythrocytes, and thrombocytes.
40
Q

Why are CLP and CMP cells referred to as transit amplifying cells?

A

They produce differentiated cells (e.g., RBCs, WBCs) and can control each lineage independently through genetic and environmental factors mediated by hormones and signaling molecules.

41
Q

What is CD34 and its significance in hematopoietic stem cells?

A
  • CD34 is a cell surface antigen expressed by rare cells, constituting less than 0.1% of the cells present in bone marrow.
  • CD34+ cells are crucial for bone marrow transplantation, although other cell types like endothelial cells also express CD34, making it non-unique as a marker for HSCs.
42
Q

How is CD34 detected and utilized in experiments?

A
  • CD34 expression is detected using antibodies that bind to the antigen.
  • These antibodies often carry enzymes that can turn substrates brown upon binding to CD34, allowing for the identification and isolation of CD34+ cells from cultures.
  • Experiments involving the removal of CD34 from bone marrow have demonstrated its necessity for bone marrow function.
43
Q

Where are hematopoietic stem cells (HSCs) typically found within the bone marrow?

A
  • Endosteum: marks the boundary between solid bone and marrow and is associated with osteoblasts, endothelial cells, and stromal cells
  • Perivascular region around vascular sinusoids: large blood vessels with thin walls comprised of fenestrated endothelium.
44
Q

What are the characteristics of the stem cell niche?

A
  • Cellular and structural components that support and regulate the function of hematopoietic stem cells.
  • In the bone marrow, this niche consists of osteoblasts, endothelial cells lining the endosteum, stromal cells composing the matrix, and vascular sinusoids.
  • HSCs can be found both lining the endosteum and in the perivascular regions adjacent to blood vessels.
45
Q

What are the proposed roles of the endosteal and vascular niches in hematopoiesis?

A

It has been suggested that the endosteal niche primarily harbors long-term, slowly dividing hematopoietic stem cells (HSCs) responsible for maintaining the vascular niche HSCs. Conversely, the vascular niche is associated with more actively dividing HSCs and the production of progenitor cells.

46
Q

How is the division of HSCs regulated within their niche?

A
  • HSC division within the niche is regulated by numerous proteins and environmental cues.
  • When an HSC divides, it gives rise to two daughter cells: one that remains within the niche and another that moves away into a different cellular environment.
  • This movement triggers changes in the daughter cell’s surroundings, influencing its behavior and division rates. Thus, the stem cell’s position within the niche is crucial for receiving signals that regulate its activity.
47
Q

What is the stem cell niche?

A

Microenvironment surrounding stem cells, providing crucial support and signals that regulate their self-renewal and differentiation.

48
Q

How are signals within the stem cell niche regulated?

A
  • Direct contact: Stem cells interact physically with neighboring cells, influencing their behavior and function.
  • Soluble factors: Growth factors and molecules like fibroblast growth factors (FGFs) are released into the niche, affecting stem cell activity.
  • Intermediate cells: Stromal cells within the niche serve as intermediaries, receiving signals from various sources and transmitting them to stem cells, indirectly influencing their behavior.
49
Q

How does asymmetric division contribute to stem cell regulation?

A
  • As the HSC divides, one cell remains within the niche, maintaining its stem cell characteristics, while the other cell moves away and differentiates into a progenitor cell.
  • This asymmetric division occurs not only in terms of cell fate but also in spatial distribution.
  • Stem cells divide asymmetrically, with one daughter cell remaining in the niche and the other moving away.
  • By moving away from the stem cell niche, the signaling inputs experienced by the daughter cell have changed, influencing its differentiation and fate.
50
Q

Why is the environment of a progenitor cell different from that of a HSC?

A
  • The progenitor cell, having moved away from the stem cell niche, experiences a different environment.
  • Growth factors present in this new environment drive its growth and subsequent differentiation.
51
Q

What is the potential role of the stem cell niche in regulating cell behavior?

A
  • The stem cell niche may play a role in slowing cell division and blocking differentiation.
  • By maintaining a specialized microenvironment, the niche influences the behavior of stem cells and their progeny.
52
Q

How have the phases of differentiation and the growth factors involved been elucidated?

A
  • Different phases of differentiation and the growth factors required have been largely worked out through cell culture experiments.
  • In vitro culture of bone marrow cells suspended in semi-solid media allows visualization of colonies derived from single cells.
  • Addition of specific growth factors and cytokines is necessary to drive both proliferation and differentiation of cells in culture.
53
Q

What are some examples of growth factors and cytokines involved in hematopoiesis?

A
  • Granulocyte/monocyte colony-stimulating factor (GM-CSF) and erythropoietin (EPO)
  • Additionally, there are others with broader activities, such as interleukin-3 (IL-3), which stimulates the growth of most hematopoietic cell types.
54
Q

What is the significance of the term “CSF” in the context of hematopoiesis?

A

“CSF” stands for colony-stimulating factor, which indicates its role in stimulating the growth and differentiation of specific types of blood cells.

55
Q

How do growth factors and cytokines exert their effects on hematopoietic cells?

A
  • They act both in a paracrine fashion, where they diffuse from the producer cell to the responder cell, and in a juxtacrine fashion.
  • In the juxtacrine mode, the ligand remains on the cell surface of the producer cell, and the responder cell’s receptor must be in direct contact with it for signaling to occur.
56
Q

How are growth and differentiation of hematopoietic cells controlled?

A
  • Control inputs come from both within the bone marrow (BM) and from sources outside the BM.
  • For example, GM-CSF may originate from lymphocytes, while EPO is produced by the kidney.
57
Q

How can infection affect the levels of growth factors in the body?

A
  • Infection can significantly increase the amount of growth factors present due to the activation of a range of leukocytes at the site of infection.
  • This heightened immune response can lead to increased hematopoiesis.
58
Q

How is EPO production regulated in response to changes in atmospheric pressure?

A
  • EPO regulation involves sensors that detect atmospheric pressure and blood flow around the kidney.
  • When pressure changes occur, the kidneys respond by producing EPO. EPO then travels to the bone marrow, where it stimulates the proliferation of RBCs and platelets, particularly if TPO production is also induced.
59
Q

What are the potential consequences of suddenly shifting hematopoietic lineage production, such as towards B cells?

A
  • Rapid changes in lineage production can disrupt the balance and lead to adverse effects.
  • For example, if platelet production decreases, it can result in anemia, highlighting the interconnectedness and importance of maintaining homeostasis in hematopoiesis.
60
Q

What does the suffix “Blast” indicate in hematopoiesis?

A

Large, proliferating cell involved in active cell division.

61
Q

What are the characteristics of reticulocytes?

A
  • Reticulocytes have a condensed and inactive nucleus, distinguishing them from actively dividing blast cells.
  • They are precursors to mature red blood cells (RBCs) and undergo further maturation steps before entering circulation.
62
Q

Describe the phases of red blood cell (RBC) development.

A

RBC development progresses through various stages, including the reticular site in the bone marrow. Before RBCs enter circulation, they must undergo denucleation, a process where the nucleus is removed.

63
Q

What is the function of blast cells in hematopoiesis?

A

Blast cells are continually producing new cells through active proliferation, contributing to the replenishment of blood cell populations.

64
Q

What role do reticular cells play in hematopoiesis?

A

Reticular cells have ceased dividing and are specialized in the process of denucleation, preparing precursor cells like reticulocytes for their final maturation into mature RBCs.

65
Q

How is platelet generation regulated, and what is the role of thrombopoietin (TPO)?

A
  • Platelet production is stimulated by TPO and other growth factors.
  • TPO is primarily produced constitutively by the liver but can double during inflammation due to cytokine interleukin-6 (IL-6).
  • Bone marrow stromal cells also produce TPO in conditions like thrombocytopenia.
  • Platelets express TPO receptors and can remove TPO from circulation, establishing a negative feedback loop to regulate platelet production.

LF266: Blood and Circulation (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions