3. ERYTHROPOIESIS Flashcards by 횐호 강

Mature erythrocytes are

Nonnucleated, biconcave discs with a central pallor that occupies one-third of the cell.

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ERYTHROCYTES Life span

120 days

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ERYTHROCYTES Main function

transports or carries oxygen from the lungs to the tissues where oxygen is released

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ERYTHROCYTES Secondary function

transports carbon dioxide from the tissues to the lungs + buffers the pH of the blood

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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

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earliest committed progenitor; gives rise to large colonies

Burst-Forming Unit-Erythroid

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gives rise to smaller colonies of RBC

Colony-Forming Unit-Erythroid

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BFU-E → mature RBC time

18- 21 days

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BFU-E → CFU-E time

1 week

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CFU-E → pronormoblast time

1 week

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Pronormoblast → mature RBC time

6 to 7 days

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The oxygen carrying component of RBC

Hemoglobin

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cell division + maturation

Normoblastic proliferation

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Erythrocyte precursor cells

Pronormoblast → Basophilic normoblast → Polychromatic normoblast → Orthochromic normoblast →
Polychromatic erythrocyte

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immature RBCs | nucleated precursors in the BM | developing nucleated
cells with normal appearance

Erythroblasts/Normoblasts

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mature RBCs

Erythrocytes

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Last stage that can undergo mitosis

Polychromatophilic normoblasts

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NORMOBLASTIC nomenclature

Pronormoblast

Basophilic normoblast

Polychromatic (polychromatophilic)
normoblast

Orthochromic normoblast

Polychromatic (polychromatophilic)
erythrocyte*

Erythrocyte

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RUBRIBLASTIC Nomenclature

Rubriblast

Prorubricyte

Rubricyte

Metarubricyte

Polychromatic (polychromatophilic)
erythrocyte*

Erythrocyte

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ERYTHROBLASTIC Nomenclature

Proerythroblast

Basophilic erythroblast

Polychromatic (polychromatophilic)
erythroblast

Orthochromic erythroblast

Polychromatic (polychromatophilic)
erythrocyte*

Erythrocyte

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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)

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blueness fades due to

ribosomes + other organelles ↓

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Basophilia is caused by

amount of ribosomal RNA

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Basic stain

methylene blue

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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

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

Polychromatic normoblast %in Bone Marrow

10%-20%

Polychromatic normoblast Bone Marrow Transit Time

30 hours

Orthochromic normoblast Nucleoli

Orthochromic normoblast %in Bone Marrow

5%-10%

Orthochromic normoblast Bone Marrow Transit Time

48 hours

Polychromatic erythrocyte Nucleoli

Polychromatic erythrocyte %in Bone Marrow

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

3. ERYTHROPOIESIS Flashcards

(96 cards)