Hematopoiesis Flashcards
Romanovsky Type Blood Stains (basic)
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
Romanovsky Type Blood Stains (acidic)
eosin - general stain for PRO (red-pink)
-Hb of RBC and granules of eosinophils
hematopoetic organs
bone marrow (RBC, granulocytes, monocytes) lymphoid organs (lymphocytes) fetal (liver)
monophyletic theory of hematopoiesis
all blood cells are derived from common pluripotential (hematopoietic) stem cell
stages of granulopoiesis
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
polyphyletic theory
each type of blood cell arises from own stem cell (not widely held theory)
blast cell appearance
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
what changes a blast must undergo to become a neutrophil
- condense nuclear chromatin (disappearance of nucleoli)
- lobulate nucleus
- appearance of cytoplasmic granules (primary/secondary)
- decrease in cytoplasmic basophilia
neutrophil promyelocyte
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
neutrophil myelocyte
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
neutrophil metamyelocyte
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
neutrophil band cell
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)
clinical use of % of neutrophil band cells
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
definitive marker of band to mature neutrophil
when segments between lobes have become thin heterochromatic filaments, and nuclei completely lobed
kinetics of neutrophil (and other granulocyte) production
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
differences in eosinophilic development
specific granules are are larger, almost black when first appear
-become pink-red as maturation continues
differences in basophilic development
specific granules are much bigger, stain purple in smears
distribution of granulocytes
marrow granulocytic reserve (MGR) - cells in bone marrow
total granulocytes in peripheral circulation (TBGP) - granulocytes in peripheral circulation
MCR is 10X TBGP
sites of hematopoiesis
flat bones of body
- sternum
- vertebrae
- ribs
- clavicles
- pelvis
- skull
components of red blood marrow
small blood vessels discontinuous sinusoids hematopoietic cords hematopoietic stem cell niche stem cells for other tissues, so can make unrejected cells
hematopoetic stem cell niche (in RBM)
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)
what blasts have to do to become RBCs
decrease cell volume
disappearance of nucleoli/nucleus
increase heterochromatin
decrease cytoplasmic basophilia, increase eosinophilia (hemoglobin)
stages of erythropoiesis
blast–> basophilic erythroblast–> polychromatophilic erythroblast–> normoblast–> reticulocyte–> orthochromatic erythroblast–> RBC
basophilic erythroblast (BEB)
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
polychromatic erythroblast (PCE)
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
normoblast (NB)
4th stage, after PCE (no more mitosis; terminal)
- cell/nucleus smaller than PCE
- totally heterochromatic
- cytoplasm mostly pink, slight blue
fates of normoblasts
80%: extrude nucleus, retain ribosomes –> reticulocyte
20%: lose residual RNA before nuclear extrusion –> orthochromatic erythroblast
orthochromatic erythroblast
same color as RBC, just nucleated
- small heterochromatic nucleus, bright eosinophilic cytoplasm
- not present in normal peripheral blood (nucleus pops out before circulation)
maturation time for RBCs
1-2 days: BEB 3 days: PCE 3 days: NB --> reticulocyte transition 1 day: reticulocyte --> RBC transition total 8-9 days
erythropoietin
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
reticular cells
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
erythroblastic island
developing RBCs that cluster around reticular cells in bone marrow, so that they can phagocytose nuclei
plasma cells
basophilic cytoplasm
negative image of Golgi
eccentically placed nucleus
“clock face” chromatin
megakaryoblast
large cell 40-50 um diameter
large/spherical nucleus b/c polyploid
homogenous basophilic cytoplasm
megakaryocyte
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
proplatelet model of platelet production
- extension of psuedopods
- formation of long extensions (proplatelets)
- platelets released from ends of proplatelets
- demarcation channels are membrane reservoir
kinetics of platelet formation
4-5 days: megakaryocyte maturation
10 days: platelets circulate
destroyed in spleen/liver, with functional mRNAs (may mitosis?)
what blasts must do to become lymphocytes
decrease cell size condense chromatin disappear nuclei acquire cell surface receptors migrate to thymus (T) or stay in bone marrow (B) for differentiation
kinetics of monocyte differentiation
2-3 days: formation in bone marrow
1-2 days: circulation
1-3 months: in tissue as macrophages
