Hematopoiesis & Homeostasis

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57 Terms

1
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cell membrane consists of

  • lipid bilayer - semi-permeable

    • hydrophobic HC tail

  • transmembrane proteins

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nucleus

contains nucleolus which produces cell’s ribosomes → ribosomes transported to cell cytoplasm for protein synthesis

3
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cytoplasm

place for protein synthesis, growth, motility, phagocytosis

organelles include

  • mitochondrion

  • ribosomes

  • endoplasmic reticulum

  • golgi appartus

  • lysosomes

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flow of genetic info in a cell

DNA replication/synthesis (nucleus)

transcription: RNA synthesis (nucleus)

translation: RNA → protein (in cytoplasm)

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protein degradation: 2 methods

to maintain homeostasis

  • lysosome system

  • ubiquitin proteasome system

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tissue homeostasis

mitotic cell division → differentiation → apoptosis

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proto-oncogenes

human genes w potential to cause cancer ie cell proliferation growth factors

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mutations in these genes → tumor

growth factors

growth factor receptors

signal-transduction proteins

transcription factors

→ activate oncogenes

cell-cycle control proteins → tumor suppressors

DNA repair proteins

pro- or anti-apoptotic proteins

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hematopoiesis is

the process that replaces circulating rbc

depends of precursor cells in BM

controlled by cytokines

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development of blood cells

3 weeks: formation of blood islands from yolk sac

6 weeks: liver = hematopoietic (HP) organ

6-8 weeks: spleen (until 8th month)

12-weeks: bone marrow (life long)

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normal BM composition

60% granulocytes & precursors

20% erythroid precursors

10% lymphocytes, monocytes

10% unID’d or disintegrated cells

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bone marrow consists of mainly _ cells

neutrophils??

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hematopoietic precursor cells

stem: 0.5%, totipotent

progenitor: 3%, multipotent

maturing: 95%, unipotent (committed)

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hematopoiesis chart

knowt flashcard image
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cytokine signaling pathways

caspase → apoptosis

Bcl2 = cell death repressor

16
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myeloid maturation

mitotic:

myeloblast

promyelocyte (primary granules)

myelocyte (secondary granules)


post-mitotic:

metamyelocyte

band

segmented neutrophil

17
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<p>myeloblasts</p>

myeloblasts

size: 8-13 um

2% nucleated cells in BM

CP: basophilic (free ribosomes), no prominent granules

NC: undifferentiated (fine chromatin, sieve-like), round to ovoid

cell division: yes

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<p>promyelocytes</p>

promyelocytes

5% of nuc’d cells in BM

size: 20 um

CP: deep blue, azurophilic granules, well developed golgi

NC: prominent nucleoli, occasionally indented, round-ovoid

cell div: yes

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<p>myelocytes</p>

myelocytes

5-20% of nuc’d cells in BM

CP: specific granules, dec in basophilia

NC: ovoid, irregular shape, nucleoli disappear, dense/compact chromatin

cell div: yes

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<p>metamyelocytes</p>

metamyelocytes

20% of nuc’d cells in BM

size: 10-18um (slightly larger than mature neutrophil)

CP: prominent secondary granules

NC: slightly indented, kidney-shaped (less than 50% indentation), dense chromatin, no nucleolus

cell div: NO

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<p>bands</p>

bands

NC: curved w no lobes (>50% indentation)

3-5% of wbc’s in adults

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<p>neutrophils</p>

neutrophils

secondary granules stain neutral pink by H&E

bright red = eosinophil

dark blue = basophil

NC: 3-5 lobes

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<p>megakaryocytes</p>

megakaryocytes

biggest cell in BM

produce plt

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erythroids development

basophilic erythroblasts

polychromatophilic erythroblast

normoblast

reticulocyte (immature rbc released into bloodstream)

25
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<p>eosinophils</p>

eosinophils

size: 12-15um

NC: 2-3 lobes

0-6%


large bright pink-orange granules

granule contains:

  • rhomboid crystals by EM

  • major basic protein which is toxic to some parasites

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<p>basophils</p>

basophils

size: 12-15um

NC: 2-3 lobes

0.5-1%


purple-black, often large coarse irregular granules which may obscure the NC

granules contain:

  • heparin

  • histamine

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<p>monocytes</p>

monocytes

largest cell in blood: 12-20um

NC: irregular, folded, or lobated w reticular chromatin

0-10%

abundant blue-gray, sometimes pale-pink CP

generally indistinct granules

CP vacuoles often seen

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<p>lymphocytes</p>

lymphocytes

greatly variable in size: 7-20um & morphology

blue CP, usually agranular

15-60% in blood

hugs rbc, thin rim of CP

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<p>plasma cells </p>

plasma cells

in BM

eccentric NC

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wbc normal counts (ANC - absolute neutrophil count)

ANC = (absolute polys + absolute bands)*1000

polys = seg neutrophils

normal >=1500 cells/mm3

mild neutropenia >= 1000-1499/mm3

moderate >=500-999/mm3

severe <500/mm3

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rbc lifespan

120 days

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plt lifespan

10 days

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granulocyte lifespan

9 hours in circulation

days in tissue

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lymphocyte lifespan

variable (hours to years) in circulation

weeks to years in tissues

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rbc size variability = anisocytosis

mean cell volume (MCV) [fL/cell]

microcytes: MCV <80

  • iron-defic anemia

  • thalassemias

macrocytes: MCV >100

  • vit B12 or folate defic

  • liver dz

normocytic: MCV 80-100 (76-96)

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rbc Hgb content

hypochromia = inc area of central pallor (>1/3 of diameter) directly due to dec amount of Hgb

  • iron-defic anemia

  • thalessemia

hyperchromia → spherocytes

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rbc shape

poikilocytosis = various shapes

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microcytic rbc

pyridoxine defic

thal

iron defic anemia

chronic dz anemia

sideroblastic anemia

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macrocytic rbc

vit B12 or folate defic

liver dz

MDS

chemotherapy (methotrexate)

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<p>spurr cells rbc (acanthocyte)</p>

spurr cells rbc (acanthocyte)

abetalipoproteinemia

liver dz

McLeod blood group phenotype

post-splenectomy

etc

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Burr cell rbc (echinocyte)

artificat

uremia

liver dz

etc

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schistocyte

microangiopathic hemolytic anemia

mechanical valve induced

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bite cell rbc

G6PD defic

unstable Hgb disorders

oxidative drugs

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elliptocyte

hereditary elliptocytosis

severe iron defic anemia

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spherocyte

hereditary spherocytosis

autoimmune hemolytic anemia

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stomatocyte

hereditary stomatocytosis

liver dz

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target cell rbc

thal

hemoglobinopathies

post-splenectomy

liver dz

artifact

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sickle cell rbc

Hgb SS dz

Hgb SC dz

Hgb SD dz

S-beta thal

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teardrop rbc

myelofibrosis

underlying marrow process/infiltrate

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Hgb C crystals

Hgb C dz

Hgb SC dz

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red cell agglutinate

cold autoimmune hemolytic anemia

paroxysmal cold hemoglobinuria

IgM assoc’d lymphoma

multiple myeloma

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rouleaux

chronic liver dz

malignant lymphoma

multiple myeloma

chronic inflammatory dz


caused by circulating abnormal proteins: monoclonal immunoglobulin/paraprotein in lymphoma/myeloma

marked hyperfibrinogenemia


reversible w dilution

  • do not affect automated CBC parameters

  • unlike rbc aggregates from immune phenomena

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<p>wbc abnormalities</p>

wbc abnormalities

Pelger-Huet nomality (autosomal dominant, all cells): bilobed or unilobed

Pseudo Pelger-Huet change (not all cells)

  • myeloid neoplasm (MDS, MPN, AML)

  • drug-induced

hypersegmented: >5

  • vit B12 or folate defic

  • myeloid neoplasm

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<p>Dohle bodies</p>

Dohle bodies

single or more blue CP inclusion

remnants of rough ER from earlier maturation stages

May-Hegglin anomaly: myosin heavy chain aggregates

associated w “left-shifts” & in conjunction w toxic granulation

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abnormal granulation

toxic granulation: severe inflammatory states, azurophilic granules

degranulation: degeneration change, dysplasia

other: congential

  • Chediak-Higashi syndrome

  • May-Hegglin anomaly

  • Alder-Reilly anomaly

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plt size

normal 2-3um

large >3 um

giant >RBC (7um)

57
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plt satellitism & plt clumping

clumped around neutrophils (satellism only)

EDTA in-vitro induced artifact

no clinical signifance

falsely low plt countp