Hematopoiesis & Homeostasis

cell membrane consists of

• lipid bilayer - semi-permeable

  • hydrophobic HC tail

• transmembrane proteins

nucleus

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

cytoplasm

place for protein synthesis, growth, motility, phagocytosis

organelles include

• mitochondrion

• ribosomes

• endoplasmic reticulum

• golgi appartus

• lysosomes

flow of genetic info in a cell

DNA replication/synthesis (nucleus)

transcription: RNA synthesis (nucleus)

translation: RNA → protein (in cytoplasm)

protein degradation: 2 methods

to maintain homeostasis

• lysosome system

• ubiquitin proteasome system

tissue homeostasis

mitotic cell division → differentiation → apoptosis

proto-oncogenes

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

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

hematopoiesis is

the process that replaces circulating rbc

depends of precursor cells in BM

controlled by cytokines

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)

normal BM composition

60% granulocytes & precursors

20% erythroid precursors

10% lymphocytes, monocytes

10% unID’d or disintegrated cells

bone marrow consists of mainly _ cells

neutrophils??

hematopoietic precursor cells

stem: 0.5%, totipotent

progenitor: 3%, multipotent

maturing: 95%, unipotent (committed)

hematopoiesis chart

cytokine signaling pathways

caspase → apoptosis

Bcl2 = cell death repressor

myeloid maturation

mitotic:

myeloblast

promyelocyte (primary granules)

myelocyte (secondary granules)

---

post-mitotic:

metamyelocyte

band

segmented neutrophil

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

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

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

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

bands

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

3-5% of wbc’s in adults

neutrophils

secondary granules stain neutral pink by H&E

bright red = eosinophil

dark blue = basophil

NC: 3-5 lobes

megakaryocytes

biggest cell in BM

produce plt

erythroids development

basophilic erythroblasts

polychromatophilic erythroblast

normoblast

reticulocyte (immature rbc released into bloodstream)

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

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

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

lymphocytes

greatly variable in size: 7-20um & morphology

blue CP, usually agranular

15-60% in blood

hugs rbc, thin rim of CP

plasma cells

in BM

eccentric NC

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

rbc lifespan

120 days

plt lifespan

10 days

granulocyte lifespan

9 hours in circulation

days in tissue

lymphocyte lifespan

variable (hours to years) in circulation

weeks to years in tissues

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)

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

rbc shape

poikilocytosis = various shapes

microcytic rbc

pyridoxine defic

thal

iron defic anemia

chronic dz anemia

sideroblastic anemia

macrocytic rbc

vit B12 or folate defic

liver dz

MDS

chemotherapy (methotrexate)

spurr cells rbc (acanthocyte)

abetalipoproteinemia

liver dz

McLeod blood group phenotype

post-splenectomy

etc

Burr cell rbc (echinocyte)

artificat

uremia

liver dz

etc

schistocyte

microangiopathic hemolytic anemia

mechanical valve induced

bite cell rbc

G6PD defic

unstable Hgb disorders

oxidative drugs

elliptocyte

hereditary elliptocytosis

severe iron defic anemia

spherocyte

hereditary spherocytosis

autoimmune hemolytic anemia

stomatocyte

hereditary stomatocytosis

liver dz

target cell rbc

thal

hemoglobinopathies

post-splenectomy

liver dz

artifact

sickle cell rbc

Hgb SS dz

Hgb SC dz

Hgb SD dz

S-beta thal

teardrop rbc

myelofibrosis

underlying marrow process/infiltrate

Hgb C crystals

Hgb C dz

Hgb SC dz

red cell agglutinate

cold autoimmune hemolytic anemia

paroxysmal cold hemoglobinuria

IgM assoc’d lymphoma

multiple myeloma

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

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

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

abnormal granulation

toxic granulation: severe inflammatory states, azurophilic granules

degranulation: degeneration change, dysplasia

other: congential

• Chediak-Higashi syndrome

• May-Hegglin anomaly

• Alder-Reilly anomaly

plt size

normal 2-3um

large >3 um

giant >RBC (7um)

plt satellitism & plt clumping

clumped around neutrophils (satellism only)

EDTA in-vitro induced artifact

no clinical signifance

falsely low plt countp