Hematopoiesis

Hematopoiesis

continuous and regulated process of blood cell production

Hematopoietic Organs

provide microenvironment for blood cells to go through differentiation and maturation

-primarily bone marrow

Functions of Growth Factors in Heatmopoiesis

stimulate proliferation

support differentiation of maturing cells

enhance function of mature cells

Hematopoiesis Sites in Embryonic/Fetal Life

yolk sac

liver (and spleen)

bone marrow

Red/Hematogenous Bone Marrow

color is produced by blood and blood-forming cells

Yellow Bone Marrow

color is produced by adipocytes and this marrow can be converted to red marrow

Red Bone Marrow Composition

stroma, hematopoietic cords, sinusoidal capillaries (w/help from reticular cells/fibers)

Stroma

three-dimensional network of reticular cells/fibers containing collagen type III, fibronectin, laminin, proteoglycans

Hematopoietic Cords

formed through hematopoietic cells and macrophages interacting with stroma through fibronection, laminin, hemonectin, and cell receptors

Main Functions of Red Bone Marrow

produce blood cells

destruct senescent red blood cells

store iron in macrophages

Pluripotential Stem Cell (PPSC)

from what blood cells arise in bone marrow

PPSC Colony Forming Units (CFUs)

multipotential lymphoid "stem" cell

Multipotential Myeloid "stem" cell

CFU-GEMM Lineage-Specific Progenitors

CFU-E

CFU-GM

CFU-Eo

CFU-Ba

CFU-Meg

CFU-L

multipotential lymphoid "stem" cell

CFU-GEMM

multipotential myeloid "stem" cell

CFU-E

progenitor giving rise to erythroid (red) lineage

CFU-GM

progeintor giving rise to neutrophil (CFU-G) and monocyte (CFU-M) lineage

CFU-Eo

progenitor giving rise to eosinophil lineage

CFU-Ba

progenitor giving rise to basophil lineage

CFU-Meg

progenitor giving rise to megakaryocytes

Precursor cells

come after lineage-specific progenitor cells and are first cells morphologically distinguishable about what cell types they'll be

SLIDE 14/TABLE 10.4

LOOK AT IT

Cell Order for Erythrocyte

proerythroblast

basophilic erythroblast

polychromatophilic erythroblast

orthochromatophilic erythroblast

reticulocyte

erythroblast

Cell Order for Mature Neutrophil

myeloblast

early neutrophilic myelocyte

late neutrophilic myelocyte

neutrophilic metamyelocyte

band cell

mature neutrophil

Cell Order for Mature Eosinophil

Myeloblast

promyelocyte

early eosinophilic myelocyte

late eosinophilic myelocyte

eosinophilic metamyelocyte

mature eosinophil

Cell Order for Mature Basophil (CHECK)

myeloblast

early basophilic myelocyte

late basophilic myelocyte

mature basophil

Erythropoiesis General Definition

development of erythrocytes from CFU-GEMM under influence of growth factors

Erythropoiesis Growth Factors

erythropoietin

granulocyte-macrophage colony stimulating factor (GM-CSF)

Interleukin-3 (IL-3)

Interleukin-4

Proerythroblast

the first recognizable erythroid precursor brought about from erythropoietin-sensitive progenitor cell CFU-E

Cell Volume in Maturing Erythrocyte

cell volume decreases

Nucleus Changes in Maturing Erythrocyte

diameter decreases

chromatin condenses

nucleus leaves towards end

Cytoplasmic Changes in maturing Erythrocyte

decreased polyribosome number (since fewer blue-synthesizing proteins)

increased hemoglobin

disappearance of mitochondria and other organelles

Dividing/Mitosing Erythrocyte Derivatives

proerythroblasts

basophilic erythroblasts

polychromatophilic erythroblasts

-and then they stop dividing

Basophilic Erythroblast to Circulation Timing

one week to reach circulation

General Erythrocyte to Circulation Timing

released to circulation almost immediately

Erythropoietin

growth factor that regulates erythrocyte formation and release

Erythrocyte lifespan

120 days

Neutrophil Development Influence

GM-CSF

Granulocyte colony stimulating factor (G-CSF)

IL-3

-induced to differentiate from CFU-GEMM through CFU-GM and CFU-G

CFU-Eo Development Influence

GM-CSF

IL-3

IL-5 (always found with Eos)

-develop from CFU-GEMM

CFU-Ba Development Influence

GM-CSF

IL-3

-develop from CFU-GEMM

Nucleus Maturation of Neutrophils, Eosinophils, Basophils

becomes more condensed and lobulated

Cytoplasm Maturation of Neutrophils, Eosinophils, Basophils

goes through two stage granule synthesis

First Stage of Granule Synthesis

Azurophilic granules (lysosomes)

Second Stage of Granule Synthesis

specific granules

-tertiary in neutrophils

Mitotic Phase of Neutrophil Maturation Duration

myeloblast to myelocyte

-lasts around one week

Post-Mitotic Phase of Neutrophil Maturation Duration

metamyelocyte to mature neutrophil

-lasts about one week

Neutrophil Circulatory Half-Life

six to eight hours

Neutrophil Tissue Apoptosis

live two days in connective tissue, then undergo apoptosis, with many lost in gastrointestinal tract lumen

Bone Marrow Major Compartments

medullary formation compartment

medullary storage compartment

Medullary Formation Compartment

bone marrow compartment made up of mitotic and maturation compartments

Medullary Storage Compartment

bone marrow compartment capable of releasing large numbers of neutrophils on demand

Vascular Compartment Major Compartments

circulating compartment

marginating compartment

Circulating Compartment

actively circulating neutrophils

Marginating Compartment

non-circulating neutrophils present in vascular space

-sequestered by vasoconstrition/endothelial adhesion and is same size as/exchanges with circulating compartment

Medullary/Vascular/Connective Tissue Compartments

medullary is five to ten times larger than vascular compartment and connective tissue compartment size is not known

CFU-GM/M Development Influences

GM-CSF

IL-3

M-CSF (monocyte colony stimulating factor)

-from CFU-GEMM

Bone Marrow Monocyte Precursors

monoblasts

promonocytes

Monoblast morphology

almost identical to myeloblast

Promonocyte

large cell with basophilic cytoplasm, large indented nucleus, lacy chromatin, nucleoli

Azurophilic Granules Development

from primary lysosomes of promonocytes

Monocyte Maturation

rapid;

CFU-M takes 55 hours

circulate for 16 hours

Platelet Production

from megakaryocytes

CFU-GEMM to CFU-Meg (GM-CSF, IL-3; thrombopoietin)

Megakaryoblast

large ovoid nucleus w/many nucleoli

-basophilic cytoplasm

-polyploid nucleus

Megakaryocyte

giant cell w/no visible nucleoi, coarse chromatin, lobulated nucleus

Demarcation formation

many invaginations of plasma membrane occur within cytoplasm during maturation

-sheds fragments that are platelets

Lymphocyte Precursors

lymphoblast

prolymphocyte

Circulating Lymphocytes

proliferate outside bone marrow, originating mainly in thymus and peripheral lymphoid organs