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Heme I Myelopoiesis
Self-study - DONE
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Medical
Graduate
03/24/2011

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Term
Normal relative concentrations of
-granulocytes,
-monocytes, and
-lymphocytes in peripheral blood
-metamyelocytes
Definition
lymphocytes: 20-50% (maj are T cells)
monocytes: 2-12%
neutrophils: 30-70%
eosinophils: 0-7%
basophils: 0-2%

metamyelocyte: 0-1%
Term
Recognize each of the major granulocytes in a peripheral blood smear
Definition
lymphocyte: dense staining, full roundish nucleus
monocyte: horseshoe
neutrophil: 3-5 lobes
eosinophil: bilobed
basophil: lots of granules, obscure nucleus
Term
Describe a PMN cell
Definition
Polymorphonuclear luekocytes
definite lobation
thread-like chromatin filaments joining 2-5 lobes
chromatin is coarsely clumped
cytoplasm is pink - lots of secondary granules
normally neutrophils are the only leukocytes to be divided into myelocyte, juvenile, band, PMN stages
45-75% in peripheral blood
Life span of 6-7 hrs
Term
Describe the formation of the hematopoietic cells and recognize the terminology used for the progenitor cells for granulocytes, monocytes, and megakaryocytes
Definition
granulocytes -> myelocyte, metamyelocyte, band cell, PMN
-neutrophilic: pink cytoplasm, fine pink (neutrophilic) secondary granules
Term
Myelopoiesis-Segmented Neutrophils
Describe the appearance (which stage of development) and function of the specific and nonspecific cytoplasmic granules
-describe which enzymes appear in the specific granules of the three types of granulocyte
Definition
Specific/secondary start to appear in the myelocyte
-basophilic: peroxidase, heparin, histamine
-eosinophilic: major basic protein
-neutrophilic: lysozyme, other proteases
-when you start to see secondary granules, it's a myelocyte

*Primary/azurophilic granules* appear in the promyelocyte
azurophil: myeloperoxidase, elastase
Term
Recognize left shifted maturation in a description of a peripheral blood smear
-"bandemia"
-examples of immature cells
Definition
More immature leukocytes

BANDEMIA:
-i/c in fraction of band neutrophils
-U-shaped nucleus, secondary or specific (neutro or baso) granules predominate
-BM is responding to stress
-neutrophils are shifting from marginated pool to circulating pool

Blasts (lymphoblasts, myeloblasts)
Promyelocytes, myelocytes, metamyelocytes
Nucleated RBC
Band neutrophils > ref range
Term
Define:
leukocytosis
neutrophilia
-mechanisms of neutrophilic leukocytosis (5 pools)
monocytosis
eosinophilia
basophilia
lymphocytosis
Definition
LEUKOCYTOSIS
-reactive: infxn, inflammation, necrosis
-malignant: leukemia (uncontrolled proliferation of leukocytes -> accumulation of leukocytic cells in BM and blood)

NEUTROPHILIC LEUKOCYTOSIS
-5 pools of neutrophils & precursors:
mitotic pool (myeloblasts, promyelocytes, myelocytes)
non-mitotic pool (metamyelocytes, bands, segment neutrophils)
peripheral blood marginating pool
peripheral blood circulating pool
extravascular tissue pool
*sampling of peripheral blood assesses only the circulating pool (can be enlarged by i/c release of neutrophils & bands from BM, d/c margination, diminished extravasation into tissues, or expansion of BM precurosr pool)
certain stimuli (acute infxn) cause changes in flux b/t multiple pools simultaneously
-in reactive neutrophilic leukocytosis:
expect left shift
bacterial infxn most common cause

MONOCYTOSIS
reactive - lots of monocytes with vacuoles
circulate ~14 hrs then migrate into tissue -> macrophages
stem cell -> monoblast (BM) -> monocyte (blood) -> macrophage (tissues)
Term
List the most common causes of neutrophilia, eosioniphilia, monocytosis, basophilia, and lymphocytosis
Definition
Neutrophilia - acute bacterial infxn

Eosinophilia - allergic, parasitic infxns

monocytosis - chronic inflammation

basophiliia - uncommon; can occur in CML

lymphocytosis - acute viral infections, ALL/CLL
Term
Define leukemoid reaction
Definition
Marked neutrophilia
Similar to leukemia - but it's not!
-reactive, self-limiting rather than leukemic
marked reactive neutrophilia with immature neutrophils
marked acceleration of leukocyte production & release
bacterial infxn, stress, etc.

WBC count - above ref range of 12,000
as high as 40,000
occurs most often with neutrophilia, but also with lymphocytes
considerable left shift
differential is chronic myelogenous leukemia or acute myelogenous leukemia if numerous myeloblasts and promyelocytes
Term
Absolute leukocyte counts
Definition
more important than relative amounts

(Total WBC count) x (% of luekocyte in differential)
Term
Terms related to leukocyte disorders:
-leukocytosis
-cytopenia
-leukopenia
-neutropenia
-lymphocytopenia
-aplastic anemia
-agranulocytopenia
-left shifted maturation
Definition
-cytosis: i/c WBC above ref range
neutrophilic, eosinophilic, basophilic
most commonly results from i/c in neutrophils
-leukopenia: decreased WBC count
-neutropenia: reduced granulocytes
-lymphocytopenia: decreased lymphocytes
<1500 cells/mm3
<700 cells/mm3: severe
-aplastic anemia: pancytopenia of the red cells, granulocytes, and platelets
-agranulocytopenia: marked reduction in granulocytes
<1000 cells/mm3
<500 cells/mm3: risk of infxns
-left shifted maturation: i/c proportion of immature cells
band forms or younger are increased
- bands, metamyelocytes, myelocytes
early release from the BM
stress, acute infxns, inflammation
Term
Granulocyte cytoplasmic changes
-myelocyte vs metamyelocyte
Definition
Metamyelocytes are slightly smaller
have kidney shaped indented nuclei & relatively dense chromatin
Cytoplasm is faintly pink, almost no blue background
secondary > primary granules
Term
Agranulocytosis
Definition
Term
Leukoerythroblastic reaction
Definition
immature red & white blood cells
due to abnormal infiltrates in the BM

space occupying lesions in the BM - metastasis and granulomas

requires BM sampling
stressed BM - has nRBCs and immature granulocytic cells, myelocytes
indicates severe disruption of the marrow
usually indicates BM has been infiltrated or replaced by secondary cancer or fibrosis, etc.
Term
What does a WBC measure?
How do you calculate absolute count?
Definition
WBC measures the relative concentration

The most imp info is the absolute count
total WBC count x the % of a specific leukocyte in the diff
Term
List the most likely leukemia in the ddx of neutrophilic leukemoid rxn
Definition
CML
AML (if lots of myeloblasts and promyelocytes)
Term
List and describe the toxic cytoplasmic changes seen in neutrophilia
Definition
Leukocytosis - high WBC count
too many neutrophils
left shift (too many young neutrophils)
absolute count within ref range

cytoplasmic vacuoles, granules, Dohle bodies
Term
Peripheral blood smear
Recognize abnormal morphology for granulocytes:
-toxic cytoplasmic changes in neutrophils (left shift)
-toxic granulations
-cytoplasmic vacuoles
-Dohle bodies
Definition
DOHLE BODIES
single or multiple blue spots, various size & shape
round or elongated
remnants of free ribo or RER
seen with toxic granules and vacuoles
seen in bacterial infxn
focal basophilia
represent aggregated ribo and whorls of RER

TOXIC GRANULATIONS
coarse purple cytoplasmic granules
seen with Dohle bodies
seen in bacterial infxn
cytoplasm of neutrophil becomes greyish blue (retention of rRNA)
less condensed chromatin
frothy or granulated cytoplasm (represents degranulation of lysosomes)
specific granules are less visible
Term
Recognize hypersegmented neutrophil
Definition
more than the usual 3-4 lobes
nucleus has 6+ lobes
larger than normal
vit B12 or folate deficiency (pernicious anemia)
dysplastic syndromes (megaloblastic anemia)
Term
Peripheral blood smear
Recognize circulating immature leukocytes
-band cells
-metamyelocytes
-myelocytes
-promyelocytes
-blasts
Definition
BLASTS
abnormal mononuclear cells that don't normally circulate in peripheral blood
immature cells, reside in BM
"nondescript" morphologically
the first stage of the granulocytic series
no cytoplasmic granulations
typical appearance is shared by lymphoblasts, myeloblasts, and circulating lymphoma cells

PROMYELOCYTES
have cytoplasmic granulations
Term
Define and recognize Auer rods
Definition
Results from the fusion of primary granules
pathognomonic of myeloid differentiation
pink or red, round or rod shaped cytoplasmic inclusions
aggregated azurophilic granules
seen in acute non-lymphocytic leukemia (leuk of granulocytic cells)
acute promyelocytic leukemia has the most granules
elongated, bluish-red rods composed of fused lysosomal granules
seen in cytoplasm of myeloblasts, promyelocytes, and monoblasts and in patients with *AML*
Term
Acute leukemia (immature stages)
Definition
*accumulation* of immature cells in BM & blood
-myelogenous
-lymphocytic

acute myeloblastic leukemia - lots of blasts
Term
Chronic leukemia (maturation)
Definition
*accumulation* of immature and mature cells (terminally differentiated) in BM & blood, but mature cells predominate
-myelogenous (myeloid)
-lymphocytic

*peripheral blood cell diff is similar to bone marrow aspirate*
-in acute: no maturation increase
Term
Define leukemia
-lymphocytic
-myelogenous
Definition
leukemia: neoplasms arising in bone marrow cells; neoplastic cells may circulate in the blood and secondarily colonize other tissue

LYMPHOCYTIC
T and B cells

MYELOGENOUS
granulocytic (neutro, baso, eos) and other cells from the myeloid stem cell mononuclear-phagocytic cells
-monocytes and macrophages
thrombocytes/megakaryocytes
Term
Hematopoiesis
recognize and define the term "blast"
Definition
The earliest recognizable myeloid cell is the myeloblast
-large round to oval nucleus
-fine diffuse immature chromatin
-prominent nucleolus
-cytoplasm is basophilic with few or no granules
-shouldn't see blast cells in peripheral blood
Term
Peripheral blood smear
Recognize the clinical significance of circulating immature granulocytes from the initial stages of maturation
-myeloblasts
-promyelocytes
-myelocytes
Definition
Leukoerythroblastic rxn
Severe disruption of the BM
BM replaced with carcinoma so BM cells are crowded out before they mature
Term
Reactive leukocytosis
-neutrophils
Definition
Reactive leukocytosis - infections, inflammation, necrosis
(compare to malignant leukocytosis - leukemia)

Neutrophilic leukocytosis - expect left shift, bacterial infxn the most common cause
Term
Recognize and explain nucleated RBC in a peripheral blood smear
Definition
Blue RBC (like a retic) with a dark purple nucleus

Can happen with anemias, thalassemias, bone marrow injury, extramedullary hematopoiesis, altered splenic function
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