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Histology > Bone marrow and Hematopoeisis > Flashcards

Bone marrow and Hematopoeisis Flashcards

1
Q

What is the main objective of hematopoiesis?

A

-synthesis of blood cells (erythropoiesis, thrombopoiesis and leukopoiesis)
-Maintenance of a constant level of each cell type in the peripheral blood

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2
Q

How does the location of hematopoiesis change over time?

A

PRENATAL:
1. Yolk sac: begins third week of gestation

  1. Hepatic phase (takes place in liver and slightly in the spleen): months 3-6
  2. Bone marrow: 3rd trimester

POSTNATAL:
4. Solely in red bone marrow

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3
Q

What is the monophyletic theory of hematopoiesis?

A

BLOOD CELLS ALL ARE DERIVED FROM A COMMON HEMATOPOIETIC STEM CELL (HSC)
-capable of self renewal and differentiation potential
-Can be identified by certain receptors in the membrane: Lin+, CD34+, CD38+, CD90+

Gives rise to 2 major colonies of oligopotent progenitor stem cells:

  1. CMP (common myeloid progenitors)
  2. CLP (common lymphoid progenitors)
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4
Q

How was the monophyletic theory of hematopoiesis experimentally derived?

A

EXPERIMENT PROCESS:
-extraction of bone marrow sample from mouse
-irradiation of sample (to create a mutation that would serve as a marker for the cells)
-implantation of irradiated sample into a new mouse that has bene irradiatied (to make space for the entrance of the new BM)

OBSERVATIONS:
1. certain markers were present in ALL leukocyte cells –> shows a common ancestor and hence existence of HSC

  1. all myeloid OR all lymphoid cells posess the same markers –> shows the presence of CLP/CMP progenitors
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5
Q

What are the changes that occur over the course of a stem cell becoming a mature cell (6)

A

General process: Stem cells –> progenitor –> precursors (blasts) –> mature cell

CHANGES:
1. Potency decrease
2. Mitotic activity increase
3. Typical morphology characteristics increase
4. Self renewal decrease
5. Differentiated functional activity increase
6. Influence of GFs on the cell peaks in the middle

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6
Q

What is a stem cell niche and what are the 2 hematopoietic stem cell niches existing?

A

STEM CELL NICHE: area of a tissue providing a certain microenvironment that stem cells are present in

  1. Endosteal: within endosteum (between solid bone wall and bone marrow) where osteoblasts are present.
    !!! HSCs are long term and slowly dividing
  2. Vascular niche: in the perivascular area around sinusoids.
    !!! HSCs are actively dividing and repsonsible for production of progenitor cells
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7
Q

What factors mediate the proliferation and differentiation of HSCs?

A
  1. INTRINSIC: transcirption factors for differentiation
  2. EXTRINSIC: cytokines or GFs (eg. colony stimulating factors)
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8
Q

General changes of characteristics that occur during erythropoiesis (5)

A
  1. decrease in cell size
  2. decrease in nuclear size, clumping of chromatin and dissapearance of nucleoli
  3. Shrinking of cytoplasm
  4. Decrease in basophilia (due to production of Hb, loss of nucleus and loss of ribosomes)
  5. Increase in cell number
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9
Q

Process of erythropoiesis steps (6)

A
  1. PRO-EB: large cell, visible nucleus and nucleoli, basophilic cytoplasm due to free ribosomes
  2. BASOPHILIC EB: increase in basophilia because RER and Golgi increase for Hb synthesis
  3. POLYCHROMATOPHILIC EB: reduced volume, Hb increase, RER decrease (regions of both basophilia and acidophilia)
    !! EPO (erythropoietin) stimulates producting of mRNA for globin
  4. ORTHOCHROMATOPHILIC EB: reduced volume, no basophilia evident as Hb is fully synthesised and RER are scarce –> uniformly acidophilic cytoplasm
  5. RETICULOCYTE: passage between orthoEB and reticulocyte shows dissapearance of nucleus. small number of RER
  6. FINAL ERYTHROCYTE: loss of ribosomes

!! EB = ERYTHROBLAST

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10
Q

What is the timeline of erythropoiesis?

A

takes 3-5 cell divisions in total, over the span of approx 1 week

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11
Q

General steps in the process of granulopoiesis: (4)

A
  1. MYELOBLAST: large cell with a nucleus and no granules present
  2. PROMYELOCYTE: synthesis of azurophilic granules in the RER (hence basophilic staining of the cytoplasm)
  3. MYELOCYTE: synthesis of specific granules in the Golgi (decreased basophilia though because AZ granules are more basophilic than spec.)
  4. METAMYELOCYTE: abundant granules in cytoplasm and a decrease in RER and Golgi bcos synthesis is complete

!! Granulopoiesis is mediated by TFs (different types for different end cells) and so after stage 4 the differentation splits for different WBC types

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12
Q

Neutrophil maturation

A
  1. Initial three stages of granulopoiesis
  2. Metamyelocyte shows a nucleus that begins to indent
  3. BAND: nucleus becomes constricted (without filament formations)
  4. SEGMENTED NEUTROPHIL: nucleus is completely segments into lobes (2-4)
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13
Q

Eosinophil maturation

A
  1. Initial 2 stages of granulopoiesis
  2. Myelocyte synthesises specific granules that are ACIDOPHILIC instead of basophilc
  3. Metamyelocyte -> start of nuclear indentation
  4. BAND: contains less lobes than neutrophil band
  5. FINAL EOSINOPHIL
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14
Q

BASOPHIL MATURATION

A

-Follows the same pattern of differentiation as eosinophils but with basophilic granules

!! only a mature basophil can be observed because they make up very low blood content and are hard to study

!! when observed , the granules are water soluble and so in slides there might be gaps in the cytoplasm where some granules have dissolved and been lost

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15
Q

Path of a neutrophil during its differentiation process (4 phases):

A
  1. MITOTIC PHASE: occurs from stem cell up to myeloblast in BM –> heavy cell differentiation lasting 1 week
  2. MATURATION: post myelocyte stages until the mature neutrophil is reached in BM
  3. Storage of the cell via attachment to endothelium of the sinusoid
  4. Release into peripheral blood circulation, giving the ability for cell migration between circulation and CT as needed
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16
Q

Process of MK maturation

A
  1. MK1: large cell with non lobed nucleus
  2. MK2: ENDOMITOSIS: duplication of nucleus without cell division –> hence nucleus occupies the majority of cell volume
  3. MK3: Sart of nucleus lobation, synthesis of azurophilic granules and an increase in RER/Golgi, visible demarcation canals for platelet formation

!! this process occurs in close proximity to sinusoid

17
Q

Process of monocyte maturation

A
  1. MONOBLAST: nucleus and nucleolus present
  2. PROMONOCYTE: larger cell with basophilic cytoplasm and larger nucleus (that has started forming chromatin indentations). Appearance of vacuoles in cytoplasm.
    !! SOME azyrophilic granules (lysosome) present but cannot be seen with H&E
18
Q

Process of lymphocyte maturation

A
  1. Occurs from CLP progenitor
  2. Pre-T/B cells
  3. B/T LYMPHOBLASTS: round nucleus, evenly stained chromatin and scarce cytoplasm
  4. B/T PROLYMPHOCYTE: smaller cell with more condensed chromatin, lacks surface markers
  5. Final B/T lymphocytes
19
Q

Development of T lymphocytes

A
  1. precursor synthesised in BM and released to mature in the thymus
  2. development occurs due to strong interaction between the thymic stroma cells and TRC receptors
  3. Lymphocyte selection:
    +VE SELECTION: production of lymphocytes showing correct affinity stimulated
    -VE SELECTION: removal of cells that show reactive potential (recognition of self antigens and damage to cells of teh organism)
  4. Migration out of thymus as mature naive cells (cells that have undergone selection in the thymus)
20
Q

Development of B lymphocytes

A
  1. Originate in the bone marrow (synthesis of precursor)
  2. Leave BM as mature nave cells with certain indentifying markers present
  3. Undergo rearrangement in these membrane markers in the lymph nodes
21
Q

Differences between red and yellow bone marrow

A

RED: contains blood vessels, sinusoids, some adipocytes and a large number of hematopoietic cells. INTENSE STAIN

YELLOW: mainly contains adipocytes and only few hematopoietic cells

!! RBM present more in children and YBM present more in elderly, althought YBM has the ability to convert to RBM and boost blood cell produciton in the case of an infection

22
Q

What are the general components of RBM?

A
  1. hematopoietic cells arranged in islands and have a cord formation
  2. sinusoids (capillaries)
  3. reticular connective stroma made of adipocytes and cellular components
23
Q

Composition of the stroma of RBM

A

-adipocytes

-meshwork of reticular fibers (collagen type 1), proteoglycans, fibronectin, laminin) –> laminin is used to interact with selectin and stabilise loaction of island cells

-reticular/adventitial cells (fibroblastic stroma cells): used for reticular fiber production

24
Q

What is the structure of the sinusoidal endothelium?

A

TRILAMINAR STRUCTURE:

  1. Luminar layer: endothelial cells (squamous epithelium)
  2. Basement membrane
  3. Adventitial cells partially covering the epithelium

!! this forms closed circulation system and means that WBCs need to use transcellular diapedesis to penetrate endothelium and enter circulation

25
Q

What is the structure of the hematopoietic cells of the RBM?

A

-arranged in groups called islands
-islands of erythroid progenitors lie in proximity to sinuoid membrane
-MK lie close to erythroid islands & sinusoids so platelets can be discharged into the sinusoid
-Granulocyte progenitor islands adjacent to sinusoids (more mature cells are closer to the sinusoid membrane than newly developing ones)
-macrophages adjacent to sinusoids in order to recycle the Hb and Fe groups released after phagocytosis of erythrocytes

26
Q

What are the ways in which we can examine bone marrow + their potential in diagnosis

A

2 methods that provide compimentary info:

  1. BM ASPIRATION: collection of aspirate (liquid bone marrow via syringe extraction), sample is smeared and visualised. ROLE: examination of morphology of individual cells
  2. BM CORE BIOPSY: extraction of bone marrow via a core. ROLE: provides BM cellularity (ratio between adipocytes and hematopoietic cells)

HYPERCELLULARITY: indicative of malignant tumours

HYPOCELLULARITY: indicates anemia (or in patients going through chemotherapy)

27
Q

What cells do CMP and CLP give rise to?

A

CMP: MYELOID: neutrophils, basophils, monocytes, eosinophils, eryhtrocytes and platelets

CLP: lymphocytes (T/B/NK)

28
Q
A

Histology (12 decks)

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