Hematopoiesis Flashcards

1
Q

Romanovsky Type Blood Stains (basic)

A

methylene blue - stains RNA-rich cytoplasm heavenly blue (esp if ribosomes)
azure B - stains DNA/GAG-rich nuclei or cytoplasmic granules of basophils/lysosomes crimson

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2
Q

Romanovsky Type Blood Stains (acidic)

A

eosin - general stain for PRO (red-pink)

-Hb of RBC and granules of eosinophils

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3
Q

hematopoetic organs

A
bone marrow (RBC, granulocytes, monocytes)
lymphoid organs (lymphocytes)
fetal (liver)
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4
Q

monophyletic theory of hematopoiesis

A

all blood cells are derived from common pluripotential (hematopoietic) stem cell

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5
Q

stages of granulopoiesis

A

development of granulocytes (neutrophils, eosinophils, basopihls)
myeloblast–> promyelocyte–> myelocyte–> metamyelocyte–> band cell–> mature cell
-first 4 only in bone marrow, last 2 in normal peripheral blood

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6
Q

polyphyletic theory

A

each type of blood cell arises from own stem cell (not widely held theory)

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7
Q

blast cell appearance

A

all blood cells start out like this (RBC, WBC, platelet)

  • large cell, 10-15 microns
  • large euchromatic nucleus
  • several nucleili
  • high nucleocytoplasmic ratio
  • numerous ribosomes (creates methylene blue stain)
  • no cytoplasmic granules
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8
Q

what changes a blast must undergo to become a neutrophil

A
  • condense nuclear chromatin (disappearance of nucleoli)
  • lobulate nucleus
  • appearance of cytoplasmic granules (primary/secondary)
  • decrease in cytoplasmic basophilia
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9
Q

neutrophil promyelocyte

A

2nd step after blast; capable of mitosis

  • same size as blast
  • spherical nucleus with slight chromatin condensation
  • nucleoli observed
  • growing appearance of primary (azurophilic) granules and primary lysozomes (w/ hydrolytic enzymes
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10
Q

neutrophil myelocyte

A

3rd step, after promyelocyte; losing ability to make DNA/RNA

  • nucleus is round/oval and more heterochromatic (azure B); more condensed, less basophilic
  • appearance of secondary (specific) granules w/ lysozyme/lactoferrin (kill bacteria)
  • -cause cytoplasmic color change from heavenly blue to salmon pink
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11
Q

neutrophil metamyelocyte

A

4th step, after myelocyte; no longer able to make DNA/RNA, or mitosis

  • kidney-shaped nucleus (beginning of lobulation), more condensed
  • no basophilic cytoplasm, and higher ratio of small specific : large azurophilic granules
  • salmon-pink cytoplasm
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12
Q

neutrophil band cell

A

5th step, after metamyelocyte; when indentation exceeds 1/2 diameter of nucleus (looks like C or S)

  • chromatin condensed, and cytoplasm looks mature
  • found in peripheral blood (1-5% total leukocytes)
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13
Q

clinical use of % of neutrophil band cells

A

provides rough indication of rate of neutrophil production in patient
-“shift to the left” - increase in % of bands in buffy coat indicates stress ins placed on bone marrow to create more neutrophils

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14
Q

definitive marker of band to mature neutrophil

A

when segments between lobes have become thin heterochromatic filaments, and nuclei completely lobed

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15
Q

kinetics of neutrophil (and other granulocyte) production

A

9-14 days (blast to mature), mostly in bone marrow
1 day in peripheral blood (circulating and marginating, exchanging between them)
5 days in surrounding tissue (diapedesis)
total life span = 15-20 days

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16
Q

differences in eosinophilic development

A

specific granules are are larger, almost black when first appear
-become pink-red as maturation continues

17
Q

differences in basophilic development

A

specific granules are much bigger, stain purple in smears

18
Q

distribution of granulocytes

A

marrow granulocytic reserve (MGR) - cells in bone marrow
total granulocytes in peripheral circulation (TBGP) - granulocytes in peripheral circulation
MCR is 10X TBGP

19
Q

sites of hematopoiesis

A

flat bones of body

  • sternum
  • vertebrae
  • ribs
  • clavicles
  • pelvis
  • skull
20
Q

components of red blood marrow

A
small blood vessels
discontinuous sinusoids
hematopoietic cords
hematopoietic stem cell niche
stem cells for other tissues, so can make unrejected cells
21
Q

hematopoetic stem cell niche (in RBM)

A

interactive structural unit that nurtures stem cells and facilitates their activity (critical for development)

  • localized supporting cells, ECM PRO, soluble factors (showing stem cells not randomly distributed)
  • found in association with spongy bone (OC/OB, etc.)
  • alterations may cause myeloproliferative disease (preleukemic condition)
22
Q

what blasts have to do to become RBCs

A

decrease cell volume
disappearance of nucleoli/nucleus
increase heterochromatin
decrease cytoplasmic basophilia, increase eosinophilia (hemoglobin)

23
Q

stages of erythropoiesis

A

blast–> basophilic erythroblast–> polychromatophilic erythroblast–> normoblast–> reticulocyte–> orthochromatic erythroblast–> RBC

24
Q

basophilic erythroblast (BEB)

A

2nd stage, after blast

  • cell/nucleus smaller than blast
  • checkerboard chromatin nucleus, loss of nucleolus
  • basophilic cytoplasm (b/c increase free ribosomes for globin production)
  • lasts 1-2 days, divides 1-2 times
25
Q

polychromatic erythroblast (PCE)

A

3rd stage, after BEB

  • cell/nucleus smaller than BEB
  • further chromatin condensation
  • gradual shift from intense basophilia to intense acidophilia (b/c increase hemoglobin and decrease ribosome) so double-staining
  • lasts 3 days, divides 3-4 times
26
Q

normoblast (NB)

A

4th stage, after PCE (no more mitosis; terminal)

  • cell/nucleus smaller than PCE
  • totally heterochromatic
  • cytoplasm mostly pink, slight blue
27
Q

fates of normoblasts

A

80%: extrude nucleus, retain ribosomes –> reticulocyte

20%: lose residual RNA before nuclear extrusion –> orthochromatic erythroblast

28
Q

orthochromatic erythroblast

A

same color as RBC, just nucleated

  • small heterochromatic nucleus, bright eosinophilic cytoplasm
  • not present in normal peripheral blood (nucleus pops out before circulation)
29
Q

maturation time for RBCs

A
1-2 days: BEB
3 days: PCE
3 days: NB --> reticulocyte transition
1 day: reticulocyte --> RBC transition
total 8-9 days
30
Q

erythropoietin

A

glycoPRO hormone

  • made in kidney (via endothelial cells)
  • increases rate of mitosis (in blasts, BEB, PCE)
  • increases RNA synthesis in developing RBCs (for Hb)
  • lessens degree of brain damage after stroke, and stimulated by hypoxia
31
Q

reticular cells

A

large cells with cytoplasmic processes (mainly phagocytosis of extruded nuclei)

  • lots of ingested material in cytoplasm
  • large, pale staining nucleus
  • plays trophic role in RBC maturation
32
Q

erythroblastic island

A

developing RBCs that cluster around reticular cells in bone marrow, so that they can phagocytose nuclei

33
Q

plasma cells

A

basophilic cytoplasm
negative image of Golgi
eccentically placed nucleus
“clock face” chromatin

34
Q

megakaryoblast

A

large cell 40-50 um diameter
large/spherical nucleus b/c polyploid
homogenous basophilic cytoplasm

35
Q

megakaryocyte

A

even larger cell (up to 150 um diameter)
lobulated nucleus
increases poidy to 32-64 n (endomitosis)
eosinophilic cytoplasm, w/ azurophilic granules
invaginations of plasma membrane throughout cytoplasm
-forms demarcation channels
-results in partitioning of cytoplasmic fragments to form platelets
-platelets enter discontinuous sinusoids in bone marrow

36
Q

proplatelet model of platelet production

A
  1. extension of psuedopods
  2. formation of long extensions (proplatelets)
  3. platelets released from ends of proplatelets
  4. demarcation channels are membrane reservoir
37
Q

kinetics of platelet formation

A

4-5 days: megakaryocyte maturation
10 days: platelets circulate
destroyed in spleen/liver, with functional mRNAs (may mitosis?)

38
Q

what blasts must do to become lymphocytes

A
decrease cell size
condense chromatin
disappear nuclei
acquire cell surface receptors
migrate to thymus (T) or stay in bone marrow (B) for differentiation
39
Q

kinetics of monocyte differentiation

A

2-3 days: formation in bone marrow
1-2 days: circulation
1-3 months: in tissue as macrophages