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clinical pathology > 4- hematopoiesis and bone marrow eval > Flashcards

4- hematopoiesis and bone marrow eval Flashcards

1
Q

In the extravascular space what is the stromal elements of the hematopoietic microenvironment

A

Stromal elements: endothelial cells, reticular (fibroblast-like) cells, adipocytes and extracellular matrix

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2
Q

in the extravascular space what are the accessory cells of the hematopoietic microenvironment

A

accessory cells: macrophages, T and B lymphocytes

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3
Q

what are the types hematopoietic cells

A
  • hematopoietic stem cells (HSC)
  • hematopoietic progenitor cells (HPC)
  • recognizable blood cell precursors
  • mature leukocyte storage pools, esp neutrophils
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4
Q

what are bone marrow stromal cells produced by

A

produced by mesenchymal stem cells

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5
Q

what do endothelial cells do in regards to bone marrow

A

they regulate the trans endothelial movement of cells btwn blood and them marrow extravascular space

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6
Q

what do reticular cells do in regards to bone marrow

A

fibroblastic-type cells they provide structural support for the bone marrow

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7
Q

what do both endothelial cells and reticular cells do

A
  • synthesis of growth factor and extracellular matrix
  • also support hematopoiesis through cell-cell contact
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8
Q

slide 9

A
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9
Q

HSCs and HPCs have what kind of appearance

A

lymphocyte appearance

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10
Q

HSCs are generally…

A

**positive for the CD34 surface antigen **

—- early HPCs are also CD34+

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11
Q

what is CD an abbreviation for

A

clusters of differentiation antigens

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12
Q

what are the properties of Hematopoietic stem cells (HSCs)

A
  • proliferation
    -sustained self replication
  • replicate slowly (once every 8-10 weeks)
  • capacity to differentiate into all blood cell types and some tissue cell types (macrophages, dendritic cells, osteoclasts, mast cells)
  • <0.0001% of nucleated cells in cat marrow
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13
Q

what do hematopoietic stem cells produce

A

common lymphoid progenitor (CLP)
— B lymphocytes, T lymphocytes, NK cells

common myeloid progenitor (CMP)
— non-lymphoid blood cells, macrophages, dendritic cells, osteoclasts, mast cells

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14
Q

what are the properties of hematopoietic progenitor cells (HPCs)

A
  • proliferation
  • limited self replication - not sustained without replenishment from HSCs
  • replicate more rapidly than HSCs
  • differentiation but with more restricted lineage potential than HSCs
  • about 1% of bone marrow cells in adults, but higher in neonates
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15
Q

what are hematopoietic growth factors (HGFs)

A

HGFs are glycoprotein cytokines that promote the proliferation, maturation, and survival of hematopoietic cells

—— HGF includes colony stimulating factors (CSFs), interleukins and poietins

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16
Q

where are hematopoietic growth factors produced

A

HGFs are produced locally in the marrow (paracrine and autocrine) and/or by cells in peripheral tissues (endocrine ex. erythropoietin from the kidney)

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17
Q

what are the early acting factors of HGFs

A

early acting factors include stem cell factor (SCF) and fIt3 ligand (FL). these factors require the presence of other cytokines

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18
Q

what are the intermediate-acting factors for HGFs

A

The intermediate-acting factors include IL3 and GM-CSF

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19
Q

what are the late acting factors for HGFs

A

late acting factors include G-CSF, M-CSF, EPO, TPO, and IL5

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20
Q

what types of indirect stimulation causes the release of HGFs

A

during inflammation, TNFa, and IL1 stimulate stromal and accessory cells to release various HGFs

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21
Q

slide 19 canine precursor cells photo

A
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22
Q

slide 20 erythropoiesis photo

A
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23
Q

what are erythroid islands

A

-erythroid cells develop around macrophages
- macrophages help create microenvironment
- phagocytize expelled nuclei and damaged or aged erythrocytes
- store iron released from phagocytized erythrocytes

add photo

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24
Q

Explain the properties of reticulocytes

A
  • formed when metarubicytes expel their nuclei, usually while still bound to macrophages
  • one rubriblast produces about 16 reticulocytes in about 4 days
  • reticulocyte maturation occurs in marrow, blood, and spleen, depending on the species
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25
what does erythropoietin (EPO) do
---- glycoprotein growth factor promotes proliferation, differentiation, and survival erythroid progenitor cells and early erythroid precursors (ex rubriblasts) inhibition of apoptosis is the main mechanism of action
26
what are the sites of EPO synthesis
renal interstitial cells (primary site in adults) - increased synthesis in response to tissue hypoxia in the kidney extrarenal production - liver, especially in the mammalian fetus - bone marrow macrophages and erythroid cells
27
neutrophil production slide 28
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what are the neutrophilic growth factors
- early and intermediate acting factors G-CSF - late acting factor --- granulocyte progenitors to myeloblasts --- increased cell division, decrease marrow transit time Cells producing various growth factors -- fibroblasts and endothelial cells -- T lymphocytes and mononuclear phagocytes
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explain eosinophil production
- marrow transit time 1 week or less - marrow storage pool like neutrophils - early and intermediate acting factors - IL5 from TH2 lymphocytes for terminal maturation
32
how are mast cells produced
mast cells progenitor (MaP) released form marrow to blood - mast cells develop in tissues -* stem cell factor promotes development *
33
what are monocytopoiesis
short generation time and little marrow reserve - M-CSF is a late activation factor stimulation monocyte production
34
monocytes may become
- *macrophages *or inflammatory *dendritic cells* in tissues - *osteoclasts* in bone marrow - depends on the amounts of various cytokines presents
35
what are osteoclasts
osteoclasts are multinucleated cells which degrade bone - develop from monocyte fusion
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lymphopoiesis - slide 41
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thrombopoiesis slide 42
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megakaryocytes properties
Depending on size - 1000 to 3000 platelets produced/ megakaryocyte --- Megakaryocytes are located just outside the vascular sinuses proplatelet processes extend into the vascular sinuses and platelets from the proplatelet processes within the vasculature
39
how are non mammals different
- no megakaryocytes - thromboblasts produce thrombocytes - the only giant cell in marrow is the osteoclast
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42
what promotes the stimulation of thrombopoiesis
early and intermediate- acting growth factors -- proliferation and expansion of megakaryocyte progenitor cells Thrombopoietin (TPO) - promotes differentiation of progenitor cells into megakaryocytes - stimulates increased endomitosis, resulting in increased ploidy and size
43
where is thrombopoietin produced
major site of production - endothelial cells of liver -- inflammatory cytokine IL6 stimulates TPO synthesis by liver during inflammation
44
what is the purpose of recombinant growth factors
recomb human EPO and G-CSF have been used to treat animals - they work for a short period of time, but antibodies are made against these glycoproteins, which limits their effectiveness These antibodies may even cross- react with animals own EPO and G-CSF, when can make matters worse dog and cat recombinant growth factors have been made, but to my knowledge are not commercially aval
45
list the reasons for bone marrow exam
- unexplained cytopenias in blood - proliferative abnormalities with unexplained left shifts, nucleated erythroid cells, or blast cells in blood - staging lymphomas or mast cell tumors - evaluate iron stores (except in cats) - evaluate focal lesions in bone (infections or neoplastic) - unexplained hyperproteinemia in blood (ex plasma cell neoplasms) - unexplained hypercalcemia (ex T-cell neoplasms)
46
what are bone marrow aspirate smears
simple, fast, relatively inexpensive -- ID individual cell types and stages with routine blood stains -- prussian blue stain for iron used for cytochemistry and immunocytochemistry to ID neoplastic cells
47
How is an aspirate collected (with anticoag)
- aspirate syringe contains EDTA in sterile saline solu - aspirate material is expelled in a petri dish and a pipette is used to collect particles to use in squash preparations (this allows for more slides to be prepped for special stains)
48
what are bone marrow core biopsys
they give a better eval of overall cellularity done after unsuccessful aspirate attempts - diagnosis of myelofibrosis - Identification of focal lesions that may occur with metastatic neoplasia, necrosis, or granulomatous inflammation
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what is evaluated during a bone marrow exam
scan for particles and est, overall cellularity - evaluate the number, morphology, and stages of megakaryocyte developments - evaluate the number, morphology, and development of erythrocytic and granulocytic cells ----------------Calculate the M:E ratio (granulocytic: erythrocytic) evaluate the number and morphology of other cell types present including lymphocytes, plasma cells, and macrophages. assess the amount of hemosiderin present
52
normal marrow cellularity on a dog
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55
what do you see regarding megakaryocytes in bone marrow aspirate
most large particles have several megakaryocytes - normally 3-15 megakaryocytes within particles per low-power field (10x) **Normally 80-90% are mature **
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how do you interpretation of M:E ratio
knowledge of overall marrow cellularity, Hct and total neutrophil count in blood is critical **- If the absolute blood neutrophil count is normal, changes in the M:E ratio generally reflect changes in the erythroid series ** **- If the Hct is normal, changes in M:E generally reflect changes in the neutrophilic series ** - if both Hct and total neutrophil count are abnormal, the interpretation is more difficult - if the marrow is markedly hypoplastic of filled with neoplastic cells, the M:E ratio is of little value
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clinical pathology (18 decks)

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