Erythropoiesis Flashcards
Mature erythrocytes are _________,
__________ with a __________ that
occupies one-third of the cell.
nonnucleated; biconcave disc; central pallor
RBC Life Span
120 days = 4 months
Main function RBC
transports or carries oxygen from the lungs to the tissues where oxygen is released
Secondary function RBC
: transports carbon dioxide from the tissues to the lungs + buffers the pH of the blood
Maturation Process of RBC
Pluripotent HSC → Common Myeloid Progenitor (CMP) → Burst-Forming Unit Erythroid (BFU-E) → + IL 3, GM-CSF, Kit Ligand → CFU-E + Erythropoietin → RBC Precursor cells → Mature RBC
➔ serves as the earliest erythroid progenitor cell
➔ It requires the following hematopoietic growth factors: IL 3, GM-CSF, Kit Ligand
BFU-E
BFU-E requires what growth factors:
IL-3, GM-CSF, Kit Ligand
➔ has fewer EPO receptors than CFU-E; hence, it does not have an absolute requirement for
EPO (kaya walang EPO sa hematopoietic growth factor ng BFU-E)
➔ can survive without EPO
BFU-E
➔ has more EPO receptors than BFU-E. This makes CFU-E a progenitor cell that has an
absolute requirement for EPO.
➔ cannot survive without EPO
CFU-E
➔ needed by CFU-E in order for it to differentiate into the earliest recognizable erythroid precursor cell (pronormoblast)
EPO
Erythroid Progenitors
BFU-E and CFU-E
earliest committed erythroid progenitor; cell gives rise to large colonies that burst
❖ Burst-Forming Unit-Erythroid
gives rise to smaller colonies
Colony-Forming Unit-Erythroid
It takes approximately _______ days for BFU-E → mature RBC
18-21
BFU-E → CFU-E Duration
1 week
❖CFU-E → pronormoblast
1 week
Pronormoblast → mature RBC
6-7 days
The cell will divide first (mitosis) and then it will be followed by the production of identical daughter cells that will undergo maturation and they will develop into the next stage.
Normoblastic Proliferation
Direct descendant of CFU-E
Pronormoblast
What happens in normoblastic proliferation:
Cell division → development of daughter cells to the next stage is only applicable from CFU-E to polychromatophilic normoblast.
Not capable of cell division, only maturation
Orthochromatophilic normoblast
mature RBCs
Erythrocytes
immature RBCs (erythroid precursor cells)
Erythroblasts/Normoblasts
still considered an erythroid precursorcell/immature RBC despite its name, “erythrocyte”
Polychromatic erythrocyte
also called Normoblasts because they are considered to be developing nucleated precursor cells in the bone marrow and they have normal appearance except for polychromatic erythrocyte
Erythroblasts
Normoblastic stage NOMENCLATURE
- Pronormoblastic
- Basophilic normoblast
- Polychromatic (Polychromatophilic) Normoblast
- Orthochromic Normoblast
- Polychromatic (Polychromatophilic) Erythorocyte
- Erythrocyte
Rubriblastic stage NOMENCLATURE
- Rubriblast
- Prorubricyte
- Rubricyte
- Metarubricyte
- Polychromatic (Polychromatophilic) erythrocyte
- Erythrocyte
Erythroblastic Stage NOMENCLATURE
- Proerythroblast
- Basophilic erythroblast
- Polychromatic (polychromatophilic)
erythroblast - Orthochromic erythroblast
- Polychromatic (polychromatophilic)
erythrocyte - Erythrocyte
CRITERIA USED IN THE IDENTIFICATION OF ERYTHROID PRECURSORS
❖ Diameter of the cell decreases
❖ Diameter of nucleus decreases more rapidly than the cell | N:C ratio decreases
❖ Nuclear chromatin pattern → coarser, clumped, condensed (raspberry-like appearance)
❖ Nucleoli disappears → cessation of protein synthesis
❖ Cytoplasm changes from blue to gray-blue (Basophilic) to salmon pink (Acidophilic/Eosinophilic)
Cell maturity is__________ proportional to the size of the cell and nucleus but _________ proportional to the size of the cytoplasm.
inversely proportional; directly proportional
➔ A condition in which the nucleus and cytoplasm mature at different rates
ASYNCHRONOUS ERYTHROPOIESIS
as the cell matures, so is the cytoplasm but with this condition, the nuclear maturation lags behind the cytoplasmic maturation
Different Rates
Usually associated with impaired DNA synthesis that is why we have cases of
erythroblastic anemia
ASYNCHRONOUS ERYTHROPOIESIS
As the cell matures, the condensation/clumping of nuclear chromatin _________ making the nucleus ________.
increases; smaller
➔ Causes the decrease in size of the nucleus
➔ Causes in the decline of nuclear activity until the nucleus become inactive and expelled
Condensation/Clumping of Nuclear Chromatin
In synthesis of proteins, we need ribosomal RNA, therefore once the nuclear activity declines, it will lead to
decline of the metabolic and synthetic
activities in the cell.
ERYTHROID PRECURSOR CELLS
First stage:
nucleoli are still present but as it develops to the next stages, nucleoli disappear
→ due to its acidic components which attract basic stain (methylene blue)
Blueness or basophilia
➔ An example of a Polychromatic stain (stains the basic and acidic components)
The cytoplasm is color blue because of the acidic components that attract the basic stain.
Basic Stain in Wright’s Stain
amount of ribosomal RNA
ribosomes + other organelles ↓, blueness fades
Basophilia
is directly proportional to the amount of acidic components (ribosomal RNA, ribosomes and other acidic components of the cell)
Basophilia
due to its basic components which attract
acid stain (eosin)
accumulation of hemoglobin
Eosinophilia
- when amounts of ribosomal RNA and ribosomes increase
Basophilia
when hemoglobin accumulation increases in the cytoplasm
Eosinophilia
correlates well with the amount of ribosomal RNA and ribosomes in the cytoplasm.
Basophilia/Blueness
correlates well with the amount of hemoglobin in the cytoplasm
Eosinophilia/Pinkness
How many mature RBCs are produced in 1 pronormoblast?
16/8-32 mature RBCs
most important in the early stages of RBC development; serves as the site for DNA and RNA synthesis
Nucleus
composed of DNA, histones and other CHONs
Chromatin
– inactive; appears more condensed; takes up basic dye (basophilic color – dark blue)
Heterochromatin
active; appears more open/granular; does not take up basic dye
Eurochromatin
site of globin synthesis and other CHONs in the cytoplasm of early erythrocyte precursors
Ribosomes
contribute to the blueness of the cytoplasm along with Ribosomes
rRNA
site of aerobic generation of energy for the
maturing cell and insertion of ferrous iron into protoporphyrin IX (heme synthesis)
Mitochondria
○ can be found freely dispersed in the cytoplasm
○ they are bound to vesicles
Iron (in the form of ferritin)
Iron can be stained using
Prussian blue
In Prussian blue, ferritin appears as small blue aggregates called
siderotic granules
What stain is used for punctate basophilia?
- Use wright stain/supravital stain
- RNA stains deeply with wright stain forming deep blue aggregates/small dots
Is it true that the best way to differentiate mature and immature RBC, aside from cell size and N:C ratio, is their chromatin pattern?
Yes. The most important criteria in the identification of the different stages of RBC maturation is their nuclear chromatin.
