3. ERYTHROPOIESIS Flashcards
Mature erythrocytes are
Nonnucleated, biconcave discs with a central pallor that occupies one-third of the cell.
ERYTHROCYTES Life span
120 days
ERYTHROCYTES Main function
transports or carries oxygen from the lungs to the tissues where oxygen is released
ERYTHROCYTES Secondary function
transports carbon dioxide from the tissues to the lungs + buffers the pH of the blood
MATURATION PROCESS 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
earliest committed progenitor; gives rise to large colonies
Burst-Forming Unit-Erythroid
gives rise to smaller colonies of RBC
Colony-Forming Unit-Erythroid
BFU-E → mature RBC time
18- 21 days
BFU-E → CFU-E time
1 week
CFU-E → pronormoblast time
1 week
Pronormoblast → mature RBC time
6 to 7 days
The oxygen carrying component of RBC
Hemoglobin
cell division + maturation
Normoblastic proliferation
Erythrocyte precursor cells
Pronormoblast → Basophilic normoblast → Polychromatic normoblast → Orthochromic normoblast →
Polychromatic erythrocyte
immature RBCs | nucleated precursors in the BM | developing nucleated
cells with normal appearance
Erythroblasts/Normoblasts
mature RBCs
Erythrocytes
Last stage that can undergo mitosis
Polychromatophilic normoblasts
NORMOBLASTIC nomenclature
Pronormoblast
Basophilic normoblast
Polychromatic (polychromatophilic)
normoblast
Orthochromic normoblast
Polychromatic (polychromatophilic)
erythrocyte*
Erythrocyte
RUBRIBLASTIC Nomenclature
Rubriblast
Prorubricyte
Rubricyte
Metarubricyte
Polychromatic (polychromatophilic)
erythrocyte*
Erythrocyte
ERYTHROBLASTIC 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)
blueness fades due to
ribosomes + other organelles ↓
Basophilia is caused by
amount of ribosomal RNA
Basic stain
methylene blue
due to its acidic components which attract basic stain
Blueness or basophilia
due to its basic components which attract acid stain
Pinkness or eosinophilia/acidophilia
Acid stain
eosin
Eosinophilia is caused by
accumulation of hemoglobin
Rubriblast (Pronormoblast) SIZE
12-19 µm
Rubriblast
(Pronormoblast) N:C RATIO
8:1
Rubriblast (Pronormoblast) NUCLEUS
Contains 1 or 2 nucleoli
Large, round nucleus
Chromatin is purple red and has a fine pattern
Rubriblast (Pronormoblast) CYTOPLASM
Deep blue (due to ribosomesRNA activity) without granules
Rubriblast (Pronormoblast) FEATURES
❖ Earliest recognizable stage
❖ High RNA activity (needed for
production of CHONs required for Hgb synthesis)
❖ Globin production begins
Prorubricyte (Basophilic Normoblast) CYTOPLASM
Deeper, richer blue
Prorubricyte (Basophilic Normoblast) FEATURES
❖ Most helpful criteria (when comparing with rubriblast): coarser chromatin and absence of nucleoli
❖ Start of hemoglobin synthesis (Hgb pigmentation not yet evident)
Prorubricyte (Basophilic Normoblast) SIZE
12-17 µm
Prorubricyte (Basophilic Normoblast) N:C
RATIO
6:1
Prorubricyte (Basophilic Normoblast) NUCLEUS
Nucleoli may be present in the early
stage but disappears later
Nuclear chromatin is deep purple red and begins to condense
Preparatory stage - produces proteins and enzymes necessary for cellular activities
Globin production
Pronormoblast
cellular activities prepared in pronormoblast stage
Hemoglobin synthesis
Iron uptake
Protoporphyrin synthesis
Rubricyte (Polychromatophilic
normoblast) SIZE
11-15 µm
Rubricyte (Polychromatophilic
normoblast) N:C RATIO
4:1
Rubricyte (Polychromatophilic
normoblast) NUCLEUS
Increased clumping of the chromatin
No nucleoli are present
Rubricyte (Polychromatophilic
normoblast) FEATURES
❖ Hemoglobin synthesis increases
(Hgb pigmentation becomes evident)
❖ Last stage capable of mitosis
❖ Polychromatophilic – many color
❖ Progressive ↓ in DNA synthesis
Rubricyte (Polychromatophilic
normoblast) CYTOPLASM
Pink (Hgb)+ blue = murky gray-blue
Two components of hemoglobin
Heme and globin
Pronormoblast can be found where
Only in bone marrow except for pathologic conditions
Metarubricyte (Orthochromic normoblast or nucleated RBC/NRBC) SIZE
8-12 µm
Metarubricyte (Orthochromic normoblast or nucleated RBC/NRBC) N:C RATIO
1:2
Metarubricyte (Orthochromic normoblast or nucleated RBC/NRBC) NUCLEUS
Chromatin pattern is tightly/completely condensed = Pyknotic nucleus
Metarubricyte (Orthochromic normoblast or nucleated RBC/NRBC) CYTOPLASM
Reddish pink
Metarubricyte (Orthochromic normoblast or nucleated RBC/NRBC) FEATURES
❖ Last nucleated stage
❖ Hgb synthesis continues
❖ Loss of vimentin (a protein which hold organelles in proper location in the cytoplasm)
❖ Nucleus expulsion or extrusion occurs
❖ Pyrenocyte (pyknotic/enveloped extruded nucleus) → engulfed by BM macrophages
Why did basophilia increase in prorubricyte
Increase rate of protein synthesis and hemoglobin
Reticulocyte (Polychromatophilic erythrocyte) N:C RATIO
wala, ulol
Reticulocyte (Polychromatophilic erythrocyte) NUCLEUS
Cell is anuclear
Diffuse reticulum
Reticulocyte (Polychromatophilic erythrocyte) CYTOPLASM
Various degrees of polychromasia (mixed pink and blue staining)
Reticulocyte (Polychromatophilic erythrocyte) FEATURES
❖ End-stage of Hgb synthesis
❖ Diffusely basophilic erythrocyte (Wright stain)
❖ Reticulocyte (Supravital stain)
❖ Endoribonuclease digests the ribosomes
❖ Resides in the BM for 1-2/2-3 days prior to its release in the PB
❖ Stays in the PB for about 1 day before becoming mature RBC
Basophilic normoblast can only be found where
Bone marrow except for pathologic conditions
Reticulocyte (Polychromatophilic
erythrocyte) SIZE
7-10 µm
Erythrocyte FEATURES
❖ Erythrocytes cannot divide
❖ No mitochondria
❖ Biconcave disc (discocyte)
❖ Hemoglobin is the cell’s main component
Erythrocyte SIZE
6-8 μm
Erythrocyte NUCLEUS
Cell is anuclear
Erythrocyte CYTOPLASM
Salmon-pink with central pale area
Metarubricyte is also known as
Nucleated red blood cell
Pronormoblast Nucleoli
1-2
Pronormoblast %in Bone Marrow
1%
Pronormoblast Bone Marrow
Transit Time
24 hours
Basophilic normoblast Nucleoli
0-1
Basophilic normoblast %in Bone Marrow
1%-4%
Basophilic normoblast Bone Marrow Transit Time
24 hours
Polychromatic normoblast Nucleoli
0
Polychromatic normoblast %in Bone Marrow
10%-20%
Polychromatic normoblast Bone Marrow Transit Time
30 hours
Orthochromic normoblast Nucleoli
0
Orthochromic normoblast %in Bone
Marrow
5%-10%
Orthochromic normoblast Bone Marrow Transit Time
48 hours
Polychromatic erythrocyte Nucleoli
0
Polychromatic erythrocyte %in Bone Marrow
1%
Polychromatic erythrocyte
Bone Marrow Transit Time
24-48 hours
contributes to the movement of nucleus to the periphery of the cell
Vimentin reduction in cell
How many are produced in 1 pronormoblast
❖ 16/ 8-32 mature RBCs
Nucleus extrusion process
Vimentin reduction
Pseudopodal movement of nucleus to cytoplasm
Pinching
Outer membrane of pyrenocyte
Phosphatidylserine
As proteins accumulate, the number of organelles gradually
diminishes
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
in the cytoplasm of early erythrocyte precursors serves as site of globin synthesis and
other CHONs
Ribosomes
site of aerobic generation of energy for the maturing cell and insertion of ferrous iron into protoporphyrin IX (heme synthesis)
Mitochondria
heme synthesis process
insertion of ferrous iron into protoporphyrin IX
🖝 can be found freely dispersed in the cytoplasm
🖝 they are bound to vesicles
Iron (in the form of ferritin)
→ferritin appears as small blue aggregates called
siderotic granules
Iron (in the form of ferritin) can be stained using
Prussian blue
Reticulocyte spend how much time in the bone marrow and in the circulation
1-2-3 days in bone marrow
24 hours in circulation to mature
Basophilic stipplings are found in
Punctate basophilic erythrocyte