Hematopoiesis & Normal Blood Cell Morphology Flashcards
1
Q
what immune tissue is considered “myeloid tissue” vs “lymphoid tissue”?
A
- myeloid tissue: bone marrow + cells derived from it (= the origin of all lymphoid precursors)
- lymphoid tissue: thymus + lymph nodes + spleen
2
Q
myeloid neoplasms are derived from?
A
all arise in the bone marrow, but may secondarily involve lymphoid tissue
3
Q
what are the sites of hematopoiesis in the fetus throughout pregnancy?
A
- 0-2 months: yolk sac in the AGM (intra-embryonic aorta-gonad-mesonephros) region
- 2-7 months: liver + spleen
- 5-9 months: bone marrow
4
Q
what are the sites of hematopoiesis after birth?
A
= bone marrow (throughout entire life)
5
Q
discuss how the hematopoietic nature of bone marrow evolves throughout adulthood
A
- infancy and childhood: ALL marrow is hematopoietic = 100% cellularity
- puberty & adulthood
- hematopoietic marrow restricted to proximal ends of femur + humeri
- cellularity calculated by: 100 - age +/- 20%
- hematopoietic marrow restricted to proximal ends of femur + humeri
6
Q
how is bone marrow cellularity calculated?
A
100-age +/- 20%
7
Q
- characterize the following cells based on CD34 expression, recognizability, relation to lineage, other properties
A
all express CD34 & are morphologically unrecognizable:
- hematopoietic stem cells
- capable of self renewel
- produce multilineage progeny
- multilineage progenitor cells
- give rise to single OR limited limited lineage progenitor cells
- progenitor cells
- irreversible lineage commitment
variable CD34 expression, first recognizable cell:
- blast cell. also, shows immuno-phenotype or cytochemistry of lineage
8
Q
which hematopoietic cell is first to commit irreversibly to a lineage?
what is its CD34 expression & recognizability?
A
progenitor cells
- express CD34
- morphologically unrecognizable
9
Q
what are the important characteristics of a blast cell?
A
- FIRST recognizable cell in a lineage
- has VARIABLE expression of CD34
- shows immunotype or cytochemistry of lineage
- last cell to be mitotically active
10
Q
discuss the stages of erythropoiesis - what characteristics are seen at each stage?
A
- pro-erythroblast
- _Hb first presen_t at this stage
- cytoplasm deeply basophillic
- large, spherical nucleus
- basophilic erythroblast
- cytoplasm still deeply basophilic
- nucleus smaller / denser chromatin
- poly-chromatophilic erythroblast
- last stage of mitotic activity
- cytoplasm is pink-blue
- nucleus has checkerboard chromatin
- ortho-chromatophilic erythroblast
- post-mitotic
- cytoplasm pink
- nucleus gets extruded
- reticulocyte
- anucleate
11
Q
which erythroblast precursors have mitotic activity?
A
- pro-erythroblast
- basophilic erythroblast
- polychromatic erythroblast (last stage with mitosis)
12
Q
which erythroblast precursor has the largest nucleus?
A
proerythrocyte
13
Q
which erythrocyte precursors have basophillic cytoplasm?
A
- pro-erythroblast (pro-normoblast)
- basophilic erythroblast
14
Q
which erythroblast precursor has pink-blue cytoplasm and why is this?
A
-
the polychromatophilic erythroblast
- hemoglobin (pink) to basophil (blue) - d/t first evidence of Hb production
15
Q
which erythrocyte precursors are post-mitotic?
A
- ortho-chromatophilic erythroblast (first one)
- reticulocyte
- mature RBC
16
Q
which erythroblast precursor has a nucleus with “checkerboard” chromatin
A
polychromatic erythroblast
17
Q
which erythroblast precursor is anucleate?
A
reticulocyte (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)
18
Q
which erythroblast precursor is anucleate?
A
reticulocyte (nucleus ingested by macrophages during ortho-chromatophilic erythroblast)
19
Q
poly-chromatophilic erythroblast in terms of
- nucleus / mitotic status
- cytoplasm color
A
- last stage of mitotic activity
- FIRST EVIDENCE of HB PRODUCTION: cytoplasm is pink-blue
- nucleus has checkerboard chromatin
20
Q
ortho-chromatophilic erythroblast in terms of
- nucleus / mitotic status
- cytoplasm color
A
- post-mitotic
- cytoplasm pink
- nucleus gets extruded
21
Q
outline the stages of granulopoiesis - what characteristics are seen at each stage?
A
- myeloblast
- large nucleus - oval shaped
- NO GRAULES - clear cytoplasm
- promyelocyte
- largest nucleus - oval shaped
- 1st stage of azurophilic granules
- myelocyte
- smaller nucleus +/- indentation
- 1st stage of specific granules (neutrophilic, eosinophilic, basophilic)
- last stage of mitotic activity
- metamyelocyte
- bean shaped nucleus
- no mitotic activity
- band form
- horseshoe shaped nucleus
- contains specific granules of only one type
22
Q
which granulocyte precursor is the largest in the lineage?
A
pro-myleocyte (second stage)
23
Q
which granulocyte precursors have mitotic activity?
A
- myeloblast
- pro-myeloblast
- myelocyte (last one)
24
Q
which granulocyte precursors are NOT mitotically active?
A
- metamyelocyte (first one)
- band form
= nucleoli not seen
25
which is the first granulocyte precursor to contain azurophilic granules?
promyelocyte
26
which granulocyte precursor is the first to contain specific granules?
myelocyte
27
which granulocyte precursor is the first to contain _only one_ specific granule?
band form
28
myelocyte
* nucleus
* granule status
* mitosis
* **smaller nucleus +/- indentation**
* **1st stage of specific granules** (neutrophilic, eosinophilic, basophilic)
* _last stage of mitotic activity_
29
metamyelocyte
* nucleus
* granule status
* mitosis
* **bean shaped nucleus**
* specific granules
* _no mitotic activity_ (first stage) = nucleoli not seen
30
band form granulocyte
* nucleus
* granule status
* mitosis
* **horseshoe shaped nucleus**
* **contains specific granules _of only one type_** - **are small & evenly distributed**
* no mitosis
31
label this photo & point out important features of cells
* bl: myeloblast
* **largest nuclei / high nuclei: cytoplasm ratio**
* **clear cytoplasm b/c NO granules**
* pro: promyelocyte
* largest cell
* smaller nuclei than myeloblast
* **presence of granules (non-specific/primary)**
* my: myelocyte
* smaller than promyelocyte
* presence of specific (secondary) granules)
* met: metamyelocyte
* smaller than myelocyte
* slight indentation
* band form
* smallest
* horseshoe shape
* **small, evenly distributed granules -** only one type of specific (secondary) granule present
32
label this photo
size: promyelocyte \> myelocyte \> metamyelocyte \> band cell
33
identify this photo & note important features
* band form
* no mitosis
* horseshoe shape
* **small, evenly distributed granules -** _only one type of specific_ (secondary) granule present
34
mature neutrophil
* nucleus separated into distinct lobes connected by a narrow filament
* granules evently distributed
35
identify the cell & note important features
monocytes
* **largest cell in normal peripheral blood**
* tho, *smaller than a promyelocyte*, which could be present in pathological conditions)
* single nucleus - indented/ lobulated / horseshoe shape
36
identify the cell & note important features
eosinophils
* bilobed nucleus
* cytoplasmic granules are _RED STAINING. spherical & evening distributed_
37
basophil
* nucleus w/ various shapes
* cytoplasmic granules are _DARK-BLUE BLACK and unevenly distributed_
38
discuss the presence of monocytes & their precursors in the blood
* **monocytes -** under normal conditions, largest cell in peripheral blood
* precursors (monoblasts & promocytes) are _NOT typically_ seen in the blood
39
lymphocytes
40
what are erythroid islands?
collections of developing **erythrocytes + macrophages** in the bone marrow
41
42
erythroid island
* E = early erythroblasts
* I = intermediate erythroblasts
* L = late erythroblasts
43
describe megakaryopoiesis
platelet generation
* nucleus undergoes multiple mitotic divisions _without cytoplasmic separation_ → **giant polyploid cell** → gets larger → sends cytoplasmic processes between endothelial cells → break into platelets
* unlike granulocytes / RBCS: platelet gets larger as it matures
* nuclei
* present in pairs of two
* attached to one another
44
identify cell, note important features
platelet - 4 nuclei
45
bone marrow & biopsy - indications
* Diagnosis and follow-up of hematolymphoid neoplasms
* Staging of lymphomas, some solid tumors
* Investigation of unexplained blood abnormality
* Fever of unknown origin, suspected bone marrow infections
* Unexplained radiographic findings
* Pre-transplantation workup
46
contraindications for bone marrow & aspiration
Not meeting any of the criteria for having one done:
* Diagnosis and follow-up of hematolymphoid neoplasms
* Staging of lymphomas, some solid tumors
* Investigation of unexplained blood abnormality
* Fever of unknown origin, suspected bone marrow infections
* Unexplained radiographic findings
* Pre-transplantation workup
47
tools for bone marrow aspiration & biopsy
* bone marrow: jamshidi needles
* bone aspiration: bone aspiration needles - smaller than jamshidi needles
48
sites for obtaining bone marrow biopsies & aspirations
* **posterior illiac crest m/c**
* ant crest alternative
* sternum - risky
49
uses of bone marrow biopsies & aspirates
* biopsies - for architectural relationships
* aspirates - for cytological evaluation of individual cells
50
list all the uses of bone marrow biopsies
* good for determining architectural relationships: estimation of
* estimation of:
* **total cellularity**: 100 - age +/- 20%
* **distribution of hematopoietic elements**
* **myeloid: erythroid relationships**
* evaluation:
* **fibrosis / infiltrating processes**
* **bony / vascular abnormalities**
51
uses of bone marrow aspirates
* **cell counts & cytological evaluation of individual cells**
* nuclear details:
* size
* presence/absence of nucleoli
* chromatin characteristics
* maturity
* cytoplasmic details
* color, granularity, inclusions
52
what are bone biopsies NOT good for?
for cytological details
53
what are bone marrow aspirates NOT good for?
for determination of architectural relationships
54
identify
characteristics, causes
normochromic normocytes
* 7.5-8 um in size
* zone of central pallor = middle ⅓ of cell
55
identify
characteristics, causes
microcytes
* characteristics
* **microcytic, hypochromic**
* \< 7.5 um
* hypochromic = _zone of central pallor \> ⅓_
* d/t lack of Hb → lack of color
* causes
* **lead to Hb deficiency**
* iron issues
* iron deficiency
* sideroblast anemia - impaired iron metabolism in RBC
* chronic anemic disease - cytokine issue; impaired macrophage-RBC hand off in RBC development
* lead/heavy metal poisoning
* thalassmia: can't make globin chains
56
identify
characteristics, causes
macrocytes
* characteristics
* \> 8 uL
* often _OVAL_ in shape
* color normal
* causes
* **vitamin deficiencies**
* **Vit-B12**
* **folate**
* neoplasms
57
identify
characteristics, causes
spherocytes
* characteristics
* **spherical** - loss of bio-concave shape → much less deformable
* due to:
* **cytoskeletal defects**
* **burns**
* **post-transfusion**
* immune hemolytic anemia
58
identify
characteristics, causes
target cells
* characteristics - **large, floppy cells with redundant membrane**
* cause - seen in hemoglobin C disease
59
identify
characteristics, causes
acanthocytes
* characteristics
* spicules that are
* _unevenly_ distributed over surface
* _unequal length_
* causes
* **a-betalipoproteinemia**
* **Liver disease**
* **Malnutrition**
60
identify
characteristics, causes
echinocytes
* characteristics
* spicules that are
* _evenly_ distributed over RBC surface
* _short, blunt_
* causes
* **liver / rental disease**
* **storage artifact**
* **enzyme deficiency**
61
identify
characteristics, causes
stomatocytes
* characteristics
* = mouth cells: **central zone of pallor** is **narrow / linear** (not rond)
* causes
* **alcohol therapy & alcoholic liver disease - m/c**
* also
* hydroxyurea therapy
* Rh null syndrome
* myelodysplastic syndromes
62
identify
characteristics, causes
schistocytes
* characteristics
* mechanical disruption of RBCs in the vasculature by fibrin strand
* causes
* **vasculitis**
* **mechanical heart valves**
* **burns**
* toxins
63
identify
characteristics, causes
sickle cells
* characteristics - cells with pointed ends
* Hb B-globin chain mutation: point mutation at position 6 replacing Glu (hydrophilic) with Val (hydrophobic) → aggregation
64
what are the components of hemoglobin C disease
* **irregularly contracted cells**
* **hemoglobin C crystals**
* _target cells_ - “floppy” cells
* _spherocyte_ - spherical, no palor
65
identify
characteristics, causes
hemoglobin C disease
* characteristics
* irregularly contracted cells - rust arrows
* hemoglobin c crystals - \*
* target cells - black arrows
* spherocyte - arrowheads
* cause:
* **Hb B-globin chain mutation**: point mutation at position 6 replacing Glu (hydrophilic) **with Lys** (hydrophobic) → aggregation
66
heinz bodies
* definition
* cause
* dx
* sequelae
* aggregates of denatured Hb adhered to the RBC cell membrane
* cause - seen in G-6-P deficiency
* dx - _seen only on supravital dyes_
* sequelae - once plucked out of RBCs by spleen, remaining RBCs = “bite cells” (degmacytes)
67
identify
characteristics, causes
bite cells (degmacytes)
* characteristics
* appear as if they have a “bite” taken out of them
* on seen on wright-stained peripheral blood smear
* cause - form after heinz bodies (hb-membrane protein aggregates d/t G-6-P deficiency) are removed by the spleen
68
on what stains are heinz bodies / bite cells seen
* heinz bodies - supravital stain (methylene blue)
* bite cell - wright-stained peripheral blood smear
69
identify
characteristics, causes
dacrocytes (tear-drop cells)
* **cause - fibrosis**
* primary - _idiopathic myelofibrosis_
* also - myeloma / solid tumors
70
identify
characteristics, causes
polychromasia
* characteristics - b**lue-gray color of immature RBCs**
* cause - **reticulocytosis:** premature release of immature cells from marrow
* regenerating marrow
* hemolytic anemia
71
polychromasia
wright-giemsa stain
72
identify
characteristics, causes
= Howel-Jolly bodies
* characteristic - small nuclear remnant present in RBC
* cause
* **post-splenectomy state**
* anemias - hemolytic, megoblastic
73
identify
characteristics, causes
pappenheimer bodies
* characteristics - **are iron-containing mitochondrial remnants**
* cause
* sideroblastic anemia
* post-splenectomy states
74
basophillic stippling
RBCs composed of RNA (**aggregates of lysosomes**)
75
* irregular clumping of RBCs
* cause - **cold agglutination**. IgM antibodies - often after m. tuberculosis infections) bind RBCs
* type II hypersensitivity reaction
76
identify
characteristics, causes
* characteristics - RBCs stack like coins
* cause - inc in certain + charge plasma proteins that \> - charge from RBCs (glycophorins) → overwhelm zeta potential → agglutination
77
post-splenectomy states can cause what kind of abnormal RBCs?
* howell-jowell bodies: nuclear remnant
* pappenheimer bodies: ferritin aggregates
78
which abrormal RBC is normal in neonates?
howell-jowell bodies
