Granulopiosis Flashcards by Noura Noura

Human stem cell

Morphological unrecognizable
Small percentage
Self renew
Multipotent

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Progenitor stem cell

Morphological unrecognizable
Small percentage
Irreversible lineage commitment

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Blast cell

The 1st recognizable cell in lineage but still u can tell lymphoyed or myloid
Mitoyicakku active

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Mature cell

Majority of cells
Deformable
Loss adherence receptor

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What are the different hematopitic stages with dates ?

Which bones ?

In fetal life :
In yolk sac until 12th week
Liver and spleen until 20 week
Bone marrow from 20 the week to adulthood

Axial bones 
Cranial 
Vertebral
Sternum 
Ribs 
Long bones
Pelvis

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How is granulopiosis under normal physiological status ?

How is granulopisis under pathological status ?

In normal status
Granuopiosis occur in the intramedullary hematopoisis ( bone marrow )

Under pathological status :
Yellow marrow converted to red ( hypercelluraity)
Liver spleen can also be resumed ( regression)
And the production will be multiplied six times

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A hierachy of cells

Multipotent hematopoitic stem cells HSC

Then the lineage commitment progenitor cells

Maturing and more granulocytes

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What are the key points of granulopoiesis ?

Highly regulated complex system of cell production

Involves proliferation and differentiation

Involves close interaction of bone marrow microenviromental elements ( stem cell niche ( with precursor cells

Cell maturation is a physiological continuum from
stem cells to cells of specific lineage granulocytes

Also i want to add this point that after cell mature stem cell nieche regulate their function as well

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What are the three components that granulopoisis depend on ?

1 . Microenviroment or bone marrow stroma ( local control )

Stem and progenitor cells
Growth factors ( humoral control )

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Granulopiosis lineage ?

HSC human stem cell
Progenitor myloid 
Myloidblast
Promyloidcyte
Myloid cyte
Metamyloid cyte 
Neutrophil

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What is the bone marrow structure ?

The bone marrow is encased by ?

Cortical bone
Transverse bone
Consists of highly organized meshwork of thin walled cappillary venous sinusis with surrounding extracellular cappillary venous sinuses with surrounding extracelluar matrx that fills the space betweeb the bony trabecule

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What is the basic structural unit of the bone marrow ?

Capillary venous sinus

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From where we take bone marrow sample and what do we take exactly ?

From the posterior superior iliac bone

We take
Bone aspirate which is like blood from red marrow
And bone marrow biopsy

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Why we need capillary venous sinus ?

We need it for the mature cells to migrate to the blood stream

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What is homing ?

Is the process by which stem cells disseminated in blood go to the bone or to the environment it want to live in by attachment to receptors ( local regulation )

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What are the cells present in bone marrow micro environment ?

Endothelial
Fibroblast
Macrophage
Adipocytes

What is the function of microenvirmonet nieche ?

Provide the molecular basis for homing of transplanted hematopoitic stem cell
Regulate differentiation and proliferation
Support survival and inhibits appoptosis

What site exactly does the granulopoisis occur ?

Erythropicysis ? Megakaroposis?

Paratropical space

Intratrobecular space then go to the middle where cappilary sinus is present and migrate to the blood stream

Give me characterstics of hematopoitic stem cells ?

Underdifferentiated
Resuide in bone marrow umbillical cord peripheral blood
Multipotent
High proliferative and self renewal capacity
Infrequent
Defined by function morphological in distinguishable
Most stem cells 95 % are out of the cell cycle they are in g0 also called quiescent

Ability to expand to generate a very large number of daughter hsc concept of stem cell transplant

So HSC are

Self renewal ( make self asymmetric divsiion
Make daughter cell differntiation
Appotosis

Granulopiosis divisions ?

Either
Stem cell asymmetric cell division
Stem make daughter and stem ( concept of bone marrow transplant )
Self renew immortal

Non stem cell symmetric division
Daughter make daughter 2
Have finite life span

HSC is

Morphologically unrecognizable
Small percentage
Self renewal
Multipotetent

Progenitor cell is

Morphologically unrecognizable
Small percentage
First irreversible lineage commitment

Blast cell

1st recognizable cell in lineage

Mitotically active

Mature cell

Majority of cells Deformable Lose adherence receptors

What is homing ?

From blood to specific site basically bone marrow

Traffliking

Process of changing hematopoitic home like from yolk sac to liver to bone marrow

Mobilization

We want the stem cells to move from bone marrow to blood so we can take it by aphorsis

What produce granulopoitic regulatory factors and name them ? Mode of action ?

Produced by bone marrow stoma ``` They include Chemokine Colony stimulating factors Interferons Interleukins Transforming growth factors Tumor necrosis factors ``` Mode of action ? Autocrine , on cells that produce them Paracrine, in cells nearby Endocrine , in cells at a distance They act synergistically or antagonistically Stimulatory and inhibitory

What are the responses of granulopoitic cell responses include ? How cell respond ?

Proliferation Differentiation Maturation Stimulation of mature function Receptor binding Transduction signal Transmitting a signal to the nucleus Stimulating the transcription of regulatory genes

Granulopoitic regulatory factors

Is a steady state granulopoisis is maintained by coordinated production of stimulatory and inhibitory cytokines produced bu BM stromal cells

What are implications of granulopisis ?

Understanding pathophysiology of diseases | Increased granulopiosis within the BM is a hallmark of acute infection or inflammation

What is the clincal implications of those factors ?

The use of granulocyte colony stimulating factor ( G-csf) Which is produced by several cell types Binds to specific receptors Activation of these receptors is followed by induction of signaling cascade Regulates proliferation and differentiation of granulocytes lineage

To whom we give granulocytes colony stimulating factors ?

Bone marrow stimulation for patients with chemotherpy induced cytopenia Also patients with bone marrow failure Also we give for donors for HSC mobilization In peripharal blood stem cell transplant

Peripheral blood stem cell transplant we give them

Granulocyte colony stimulating factor

Talk about the kinetics of granulopoisis ?

``` Myeloblast ( first distinguisble + highly mitotic ) Promyelocyte mitotic Myelocyte Metamyelocyte Band cell Neutrophils ```