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Vertebral Column > Bone Marrow and Haematopoiesis > Flashcards

Bone Marrow and Haematopoiesis Flashcards

1
Q

What is haematopoiesis?

A

The process of production of mature blood cells from pluripotent stem cells and haematopoietic stem cells.

A restricted number of blood stem cells give rise to a differentiated progeny of at least 10 distinct lineages, while maintaining a population of haematopoietic stem cells capable of sustaining blood formation throughout the lifespan of the organism.

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2
Q

When and where do the first traces of blood formation occur in the embryo?

A

Occur around day 17 in the extraembryonic splanchnic mesoderm surrounding the yolk sac.

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3
Q

What induces the formation of haemangioblastic aggregates?

A

Mesoderm association with the yolk sac

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4
Q

Haemangioblastic aggregates differentiate into 2 cell lineages. What are they?

A
  • Endothelial precursor cells
  • Primitive haematopoietic stem cells (develop in 2 waves)
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5
Q

What do endothelial precursor cells (angioblasts) differentiate into?

A
  • Endothelial cells
    • Through vasculogenesis, these form capillaries
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6
Q

Describe primitive haematopoiesis

A
  • First wave
  • Emerge at mid to late primitive streak stage
  • Gives rise to:
    • Primitive erythropoietic cells
    • Primitive macrophages
    • Primitive megakaryocytes
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7
Q

Describe difinitive haematopoiesis

A
  • Second wave
  • Definitive haematopoietic stem cells and multipotent
  • Arise in the placenta and aorta-gonad-mesonephros region.
  • From there, cells migrate into the fetal livel, spleen and eventually (just before birth) bone marrow.
  • Finished by day 40.
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8
Q

Draw a rough diagram to illustrate the pathway of definitive haematopoietic stem cells

A
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9
Q

From which type of cell do erythroblast progenitors develop?

A

Common myeloid precursors

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10
Q

Where to primitive erythrocytes mature?

A

In the blood stream

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11
Q

How many generations are there between the erythroid stem cell and the erythrocyte?

A

At least 5 generations

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12
Q

Where do difinitive erythrocytes mature?

A

In the fetal liver

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13
Q

What are erythropoietic stem cells formed of?

A

Nucleated erythrocytes containing embryonic haemoglobin

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14
Q

What is the difference between embryonic, fetal and adult haemoglobins?

A

The stability of the subunit interference

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15
Q

Describe the primitive red cells

A
  • 6 times larger than the adult red blood cell
  • Express genes for embryonic and adult haemoglobin
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16
Q

What is the principal site of blood production of all mature circulating blood?

What is the one exception to this?

A
  • The bone marrow = principal site
  • Exception = T cells. These require the specialised microenvoronment of the thymus to complete their development.
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17
Q

Samokhvalov et al. (2007) on haematopoietic stem cells

A
  • Some adult haematopoietic stem cells have extraembryonic origin.
  • Samokhvalov et al. (2007) demostrated the migration of haematopoietic stem cell progenitors from the yolk sac to the fetal liver and thymus.
    • ​In turn, showed that yolk sac blood island contains precursors to adult haematopoietic stem cells.
  • Conclusion: yolk sac normally contributes to the adult haematopoietic system, but the extent of its contribution is yet to be determined.
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18
Q

What happens to haematopoietic stem cells in the fetal liver and why?

A

HSCs expand in the fetal liver so as to make up the number of stem cells necessary to sustain haematopoiesis in the adult.

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19
Q

What is the mark of a true haematopoietic stem cell?

A

Capacity to long-term reconstitute the haematopoietic system of the adult.

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20
Q

What happens to haematopoietic stem cells after their expansion in the fetal liver?

A

They eventually migrate to the bone marrow cavities of the axial skeleton perinatally, where adult haematopoiesis becomes definitively established.

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21
Q

Describe the haematopoietic capacity of the adult liver

A
  • Haematopoietic potential of the liver is retained in the adult
  • Demonstrated by the extramedullaet erythropoiesis that occurs in the liver or spleen at times of severe bone marrow dysfunction.
    • Extramedullary erythropoiesis in the adult is rare.
  • Schlitt et al. (1995) - extramedullary erythropoiesis in the liver and reconstitution of multilineage haematopoiesis by donor-derived cells has been reported following liver transplantation in adult humans with normal bone marrow function.
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22
Q

Desribe the bone marrow

A
  • Primary site of haematopoiesis in adults
  • Primary lymphoid tissue
  • One of the biggest organs in the human body
  • Interstices of trabecular bone form the medullary cavity, which contains the bone marrow.
  • Found in the central parts of long bones and some bones of the axial skeleton.
  • Accounts for ~5% of body weight
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23
Q

What are the 3 components of bone marrow?

A
  • Red marrow (haematopoietically active)
  • Yellow marrow (inactive)
  • Osseous
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24
Q

Describe the bone marrow in the fetus

A
  • In the neonate, virtually the entire bone marrow cavity is occupied by proliferating haematopoietic cells.
  • Haematopoiesis at this stage even occurs in the phalanges!
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25
Q

What happens to the bone marrow as a child ages?

A

Haematopoietic marrow contracts centripitally, being replaced by fatty marrow.

26
Q

In which parts of the adult skeleton is haematopoiesis confined to?

A
  • Skull
  • Vertebrae
  • Ribs
  • Clavicles
  • Sternum
  • Pelvis
  • Proximal half of humeri
  • Proximal half of femora
  • Large amount of variation between indviduals
  • The volume of the marrow cavity occupied by haematopoietic tissue expands in response to demand.
27
Q

Describe the structure of bone marrow

A
  • Haematopoietic tissue islands and adipose cells surrounded by vascular sinuses, interspersed within a meshwork of trabecular bone.
  • Extensive blood supply.
  • 2 compartments:
    • Stroma - framework of mesenchymal stem-cell-originated adipose cells, stromal cells, fibroblasts, macrophages and blood vessels interspersed with trabeculae.
    • Parenchyma - spongy network of haematopoietic cells.
28
Q

Describe pathology of the bone marrow of the intervertebral disc

A
  • Vertebral bone marrow is involved in IV disc nutrition
  • Fat conversion is suspect to participate in disc degeneration
29
Q

Describe the vascular supply to the bone marrow

A
30
Q

Describe red marrow

A
  • Abundant in neonates
  • Contains haematopoietic cells
  • Mainly localised in metaphysis of long bones
  • Conversion from red → yellow marrow occurs throughout childhood
  • Conversion starts in the limbs and continues proximally, then proceeds into the axial skeleton.
  • 40% water
  • 40% fat
  • 20% protein
31
Q

Describe yellow marrow

A
  • Largely adipose tissue
  • Found in appendicular skeleton of adults
  • Mainly localised in diaphysis and epiphyses of long bones
  • Accounts for ~7% of all body fat
  • 80% fat
  • 15% water
  • 5% protein
32
Q

Describe the function of bone marrow adipocytes

A
  • Like other adipocytes, bone marrow adipocytes are secretory cells.
  • They have not only a simple function of storage, but are involved in secreting numerous adipokines in the bone marrow environment (particularly leptin and adiponectin).
  • Bone marrow adipocytes and osteoblasts have a common origin (mesenchymal stem cell).
    • Common origin results in competition between alternative differentiation towards adipogenesis or osteogenesis
33
Q

What do common lymphoid progenitor cells give rise to?

A
  • T cells
  • B cells
  • Natural killer cells
34
Q

What do common myeloid progenitor cells give rise to?

A
  • Red blood cells
  • Basophils
  • Neutrophils
  • Eosinophils
  • Maacrophage
  • Mast cells
  • Platelets
35
Q

Draw a flow chart to illustrate the production of mature blood cells from pluripotent stem cells and haematopoietic stem cells.

A
36
Q

Describe erythrocytes

A
  • Life span - ~120 days
  • Anucleated
  • Biconcave disc
  • Main function is gas exchange
  • Have heme-containing protein: haemoglobin, which binds the O2 and CO2
  • The shape of erythrocytes provides a high level of flexibility required for passage through the small diameter capillaries.
37
Q

What aspect of the structure of an erythrocyte withstands shear during circulation?

A
  • In addition to the lipids, proteins and carbohydrates, erythrocyte plasma membrane has a cytoskeleton.
  • Cytoskeleton formed of cross-linked proteins which withstand shear during circulation.
38
Q

Describe leukocytes

A
  • White blood cells
  • Responsible for immunity:
    • Defend against pathogens
    • Remove damaged cells
    • Remove toxins
  • Contain nucleus and other organelles
  • All leukocytes (except lymphocytes) are non-specific
  • Classified into granulocytes and agranulocytes
    • Both types contain secretory vesicles and lysosomes
39
Q

List the types of granulocytes

A
  • Eosinophils
  • Neurtophils
  • Basophils
40
Q

List the types of agranulocytes

A
  • Monocytes
  • Lymphocytes
41
Q

Describe eosinophils

A
  • Bi-lobed nucleus
  • Granules stain bright red
  • Attack foreign bodies by releasing toxins - nitric oxide, cytotoxic enzymes, or by phagocytosing foreign bodies.
  • These cells are also able to resist the inflammatory actions of neutrophils and mast cells.
42
Q

Describe basophils

A
  • Contain heparin and histamines
  • Functionally related to the mast cell
  • The main function of basophils is to release heparin and histamines at the site of injury.
    • Released agents cause vasodilation and prevent blood clotting, ensuring blood supply to the site of injury.
  • The least numberous white blood cells.
43
Q

Describe neutrophils

A
  • Most abundant white blood cells
  • Polymorphous nucleus
  • Life span of ~10 hours
  • Induce inflammation by releasing prostaglandins.
  • Engulf foreign material
    • Vesicle of engulfed bacterium fuses with enzyme lysosomes destroying the foreign body.
  • Cytoplasm contains many small, specific granules and larger azurophilic granules, which contain enzymes.
44
Q

Describe monocytes

A
  • Kidney-shaped nuclei
  • Largest leukocyte
  • Life span in the blood of ~3 days
  • Develop into macrophages after activation
  • Macrophages can phagocytose large cells and debris
  • Release signals to attract other leukocytes to the site of injury.
45
Q

Describe lymphocytes

A
  • Most abundant agranulocyte
  • Responsible for specific immune system response to infection
  • Regulates inflammation
  • Types of lymphocytes:
    • T cells
    • B cells
    • Natural killer cells
46
Q

Describe the different types of T cells

A
  • T lymphocyte subgroups differ in the antigenic markers they have and their function.
  • Cytotoxic T cells - attack foreign cells
  • Helper T cells - activate B cells
  • Suppressor T cells - inhibit T and B cell activity
47
Q

What do active B cells do?

A

Differentiate into plasma cells to produce and release antibodies.

48
Q

Describe natural killer cells

A
  • Recognise foreign cells and attack by attaching onto the target cell.
  • NK cells release vesicles that cover the cell membrane.
  • The release of the perforin from the vesicles completely destroys the membrane of a foreign cell as well as breaking the cell apart.
49
Q

Describe platelets

A
  • Fragments of megakaryocytes
  • Life span is ~10 days
  • Change shape after activation from round discs to a sphere with dendritic extensions.
  • Contain secretory granules which secrete various proteins, reinforce platelet aggregation and platelet-surface coagulation reactions.
50
Q

Describe reconversion

A
  • Replacing of yellow marrow with haematopoietic cells.
    • The reverse of the natural conversion process
  • In response to the haematopoietic needs of the body:
    • Non-medical conditions:
      • Smoking cigarettes
      • Doing sports with a high oxygen debt
    • Medical conditions:
      • Obesity and related respiratory disorders
      • Diabetes
      • Chronic conditions related to anaemia
      • Patients treated with haemtopoietic growth factors
  • Occurs when the haematopoietic capacity of existing red marrow stores is exceeded.
51
Q

Poulton et al. (1993) on bone marrow reconversion in heavy smokers

A
  • Study found significant differences between marrow reconversion in smokers and non-smokers.
  • Hyperplasia of erythroid cells is found in smoking patients with polycythemia.
    • Hypothesis: this accounts for reconversion phenomenon in heavy smokers.
    • Explanation: process occurs as a result of tissue hypoxia from increased carboxyhaemoglobin and resultant stimulation of erythrocyte production.
    • Limitation of study: any red marrow in atypical locations was considered reconversion. Did not take into account the possibility that not all conversion had occurred by age 25.
52
Q

Describe neoplastic marrow infiltrate disorders

A
  • Fatty marrow is replaced with neoplastic tissue
  • Marrow can be infiltrated as a result of neoplastic diseases:
    • Lymphoma
    • Leukaemia
    • Multiple myeloma
    • Metastases
  • Metastases localise in the red marrow becasue it has a richer blood supply than fatty marrow.
  • Most common site of metastatic diseases is the vertebral column (69%).
53
Q

Describe fibrotic marrow infiltrate disorders

A
  • Fatty marrow is replaces with fibrotic tissue
  • Infiltration occurs as a result of fibrosis:
    • Osteomyelitis: infiltration of the marrow by inflammatory cells
    • Marrow infarction: obstruction of the medulla
      • Results from either malignant infiltration of the marrow with consequent elevation of intraosseous pressure or it can be secondary to chemotherapy or steroid administration.
      • Can also be seen in patients with sickle cell disease.
54
Q

Describe myeloid depletion

A
  • Loss of normal red marrow
    • Pathologically, the marrow is acellular or hypocellular.
    • Yellow marrow fills the marrow space.
  • Initial pathological changes as a result of myeloid depletion are:
    • Edema
    • Vascular congestion
    • Diminished haematopoiesis
  • Caused by:
    • Viral infections
    • Some medications
    • Chemotherapy / radiation therapy
    • In many cases, cause is unknown
55
Q

Describe myelofibrosis

A
  • Replacement of normal marrow cells with fibrotic tissue
  • Usually caused by chemotherapy or radiation therapy
  • Occasionally occurs as a primary disorder
56
Q

What is hyperplasia?

A
  • Abnormal increase in number of cells in an organ or tissue.
  • In the bone, it is a process of repopulation of yellow marrow by red marrow.
  • Mechanism of reconversion, caused by an increased demand for haematopoiesis.
  • Hyperplasia may involve cell lineages or just an individual cell line.
57
Q

What effect can hyperplasia have on the vertebral column?

A

Can cause increased numbers of all haematopoietic cell lineages (erythrocytes, myeloid and megakaryocitic cells) by 50-95%, which can disrupt the trabeculae of the bone and result in osteoporosis.

58
Q

What is hypoplasia?

A
  • The underdevelopment of a tissue or organ.
  • In the bone, hypoplasia is a replacement of haematopoietic marrow with yellow marrow.
  • Mechanism of myeloid depletion
  • Caused mainly by chemotherapy and radiotherapy
59
Q

Describe thalassaemia

A
  • Results from diminished or absent production of one or more globin chains.
    • Causes imbalanced globin chain production.
  • Excess globin chains form tetramers and precipitate within erythrocytes.
    • Leads to chronic haemolysis in bone marrow and peripheral blood.
  • Severity varies based on type of mutation or deletion.
  • α or β subgroups of thalassaemia.
  • Extramedullary haematopoiesis occurs in diseases with chronic overproduction of erythrocytes.
60
Q

Describe the possible effect of thalassaemia on the vertebral column

A

Spinal cord compression by epidural extramedullary haematopoietic tissue.

61
Q
A

Vertebral Column (13 decks)

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