Erythropoiesis Flashcards

1
Q

What are erythroblasts and what do they produce?

A
  • The nucleated precursors in the bone marrow
  • Produce progenitors, burst-forming unit–erythroid (BFU-E) and colony-forming unit–erythroid (CFU-E), both committed to the erythroid cell line
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2
Q

What are the criteria (4) used in erythroid precursor identification?

A
  • Cell size -decreases
  • Nucleus size - decrease
  • Chromatin pattern
    • Coarser, clumped, and condensed.
    • Size
    • Nuclear-cytoplasmic (N:C) ratio
    • Nucleoli
  • Cytoplasm
    • Color
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3
Q

What are the cells that make up the Normoblastic System?

A
  • Pronormoblast/rubriblast (first recognized precursor)
  • Basophilic normoblast/prorubricyte
  • Polychromatic normoblast/rubricyte - where cell division stops
  • Orthochromic normoblast/metarubricyte
  • Polychromatophilic Erythrocyte/Reticulocyte
  • Erythrocyte
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4
Q

What is Polychromatophilia and what cell is it seen in?

A
  • Purplish-pink hue in reticulocytes
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5
Q

What stain is commonly used in a blood smear?

A
  • modified Romanowsky stain, such as Wright or Wright-Giemsa
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6
Q

What elememts make up a nuclear chromatin pattern?

A
  • texture, density, homogeneity
  • nuclear diameter
  • nucleus:cytoplasm (N:C) ratio
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7
Q

What happens to cytoplasm as erythrocytes mature?

A
  • Cytoplasm color changes from the gray blue to salmon. The amount of ribosomal RNA decline from the earlier stage and there is an increase in the hemoglobin formation. The cytoplasm becomes less basic
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8
Q

What happens to nucleoli as erythrocytes mature?

A
  • Nucleoli disappear -Nucleoli represent areas where the ribosomes are formed and are seen early in cell development as cells begin actively synthesizing proteins. As RBCs mature, the nucleoli disappear, which precedes the ultimate cessation of protein synthesis
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9
Q

What happens to chromatin/nucleus as erythrocytes mature?

A

-nucleus undergoes pyknosis, or karyopyknosis, which is the irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis

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10
Q

Pronormoblast:

- Nuclear features?

A
  • The nucleus takes up much of the cell (N:C ratio of 8:1). The nucleus is round to oval,containing one or two nucleoli. The purple red chromatin is openand contains few, if any, fine clumps.
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11
Q

Pronormoblast:

- Cytoplasmic features?

A

-The cytoplasm is dark bluebecause of the concentration of ribosomes. The Golgi complex may be visible next to the nucleus as a pale, unstained area. Pronormoblasts may show small tufts of irregular cytoplasm along the periphery of the membrane

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12
Q

Pronormoblast:

- Number of divisions?

A

-The pronormoblast undergoes mitosis and gives rise to two daughter pronormoblasts. More than one division is possible before maturation into basophilic normoblasts.

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13
Q

Pronormoblast:

- Location in body?

A
  • The pronormoblast is present only in the bone marrow in healthy states
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14
Q
Basophilic Normoblast (Prorubricyte):
- Nuclear features?
A
  • The chromatin begins to condense, clumps along the periphery of the nuclear membrane the parachromatin areas become larger and sharper, and the N:C ratio decreases to about 6:1. The chromatin stains deep purple-red. Nucleoli may be present early in the stage but disappear later.
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15
Q
Basophilic Normoblast (Prorubricyte):
- Cytoplasmic features?
A
  • the cytoplasm may be a deeper, richer bluethan in the pronormoblast
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16
Q
Basophilic Normoblast (Prorubricyte):
- Number of divisions?
A
  • undergoes mitosis, giving rise to two daughter cells. More than one division is possible before the daughter cells mature into polychromatic normoblasts.
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17
Q
Basophilic Normoblast (Prorubricyte):
- Location in body?
A
  • only in the bone marrow in healthy states
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18
Q

Basophilic Normoblast (Prorubricyte):

  • Cellular activity?
  • Lifespan?
A
  • Cellular activity - hemoglobin synthesis occur

- Lifespan - lasts slightly more than 24 hours

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19
Q
Polychromatic normoblast (rubricyte)
- Nuclear features?
A
  • CHROMATIN PATTERN VARIES DURING THIS STAGE OF DEVELOPMENT, SHOWING SOME OPENNESS EARLY IN THE STAGE BUT BECOMING CONDENSED BY THE END. THE CONDENSATION OF CHROMATIN REDUCES THE DIAMETER OF THE NUCLEUS CONSIDERABLY, SO THE N:C RATIO DECREASES FROM 4:1 TO ABOUT 1:1 BY THE END OF THE STAGE. NOTABLY, NO NUCLEOLI ARE PRESENT.
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20
Q
Polychromatic normoblast (rubricyte)
- Cytoplasmic features?
A
  • FIRST STAGE IN WHICH THE PINK COLOR ASSOCIATED WITH STAINED HEMOGLOBIN CAN BE SEEN. THE STAINED COLOR REFLECTS THE ACCUMULATION OF HEMOGLOBIN PIGMENTATION OVER TIME AND CONCURRENT DECREASING AMOUNTS OF RNA
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21
Q
Polychromatic normoblast (rubricyte)
- Number of divisions?
A
  • LAST STAGE IN WHICH THE CELL IS CAPABLE OF UNDERGOING MITOSIS, ALTHOUGH LIKELY ONLY EARLY IN THE STAGE
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22
Q
Polychromatic normoblast (rubricyte)
- Location in body?
A
  • POLYCHROMATIC NORMOBLAST IS PRESENT ONLY IN THE BONE MARROW IN HEALTHY STATES
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23
Q
Polychromatic normoblast (rubricyte)
- Life span?
A
  • THIS STAGE LASTS APPROXIMATELY 30 HOURS
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24
Q
Polychromatic normoblast (rubricyte)
- Cellular activity?
A
  • HEMOGLOBIN SYNTHESIS INCREASES, AND THE ACCUMULATION BEGINS TO BE VISIBLE IN THE COLOR OF THE CYTOPLASM. CELLULAR ORGANELLES ARE STILL PRESENT, PARTICULARLY RIBOSOMES, WHICH CONTRIBUTE A BLUE ASPECT TO THE CYTOPLASM. THE PROGRESSIVE CONDENSATION OF THE NUCLEUS AND DISAPPEARANCE OF NUCLEOLI ARE EVIDENCE OF PROGRESSIVE DECLINE IN TRANSCRIPTION OF DEOXYRIBONUCLEIC ACID (DNA)
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25
Q
Orthochromic normoblast (metarubricyte)
- Nuclear features?
A
  • THE NUCLEUS IS COMPLETELY CONDENSED (PYKNOTIC)
26
Q
Orthochromic normoblast (metarubricyte)
- Cytoplasmic features?
A
  • NCREASE IN THE SALMON-PINK COLOR OF THE CYTOPLASM REFLECTS NEARLY COMPLETE HEMOGLOBIN PRODUCTION. THE RESIDUAL RIBOSOMES REACT WITH THE BASIC COMPONENT OF THE STAIN AND CONTRIBUTE A SLIGHTLY BLUISH HUE TO THE CELL, BUT THAT FADES TOWARD THE END OF THE STAGE AS THE ORGANELLES ARE DEGRADED
27
Q
Orthochromic normoblast (metarubricyte)
- Number of divisions?
A
  • not capable of division due to the condensation of the chromatin
28
Q
Orthochromic normoblast (metarubricyte)
- Location in body?
A
  • present only in the bone marrow in healthy state
29
Q
Orthochromic normoblast (metarubricyte)
- Cellular activity?
A
  • Hemoglobin production continues on the remaining ribosomes using messenger RNA produced earlier
30
Q

Orthochromic normoblast (metarubricyte)

  • What are Howell-Jolly bodies?
  • How are they removed?
A
  • small fragments of nucleus left behind if the projection is pinched off before the entire nucleus is enveloped
  • typically removed from the cells by the splenic macrophage pitting process once the cell enters the circulation
31
Q
Orthochromic normoblast (metarubricyte)
- What happens to the nucleus?
A
  • the nucleus is ejected from the cell. The nucleus moves to the cell membrane and into a pseudopod-like projection. The enveloped extruded nucleus, called a pyrenocyte, is engulfed by bone marrow macrophages
32
Q

Polychromatic RBC

- Nuclear features?

A
  • No nucleus
33
Q

Polychromatic RBC

- Cytoplasmic features?

A
  • predominant color of hemoglobin. By the end of the polychromatic erythrocyte stage, the cell is the same color as a mature RBC, salmon pink. It remains larger than a mature cell, however. The shape of the cell is not the mature biconcave disc but is irregular
34
Q

Polychromatic RBC

- Cell division?

A
  • none, no nucleus
35
Q

Polychromatic RBC

- Location in the body?

A
  • resides in the bone marrow for 1 day or longer and then moves into the peripheral blood for about 1 day before reaching maturity. retained in the spleen for pitting of inclusions and membrane polishing by splenic macrophages, which results in the biconcave discoid mature RBC
36
Q

Polychromatic RBC

- Cellular activity?

A
  • completes production of hemoglobin from residual messenger RNA using the remaining ribosome. A small amount of residual ribosomal RNA is present, however, and can be visualized with a vital stain such as new methylene blue, so called because the cells are stained while alive in suspension (i.e., vital), before the film is made
37
Q

Reticulocyte

- Cytoplasmic features?

A
  • reticulum of a polychromatic erythrocyte (reticulocyte) is not seen using Wright stain.
  • ## residual RNA imparts the bluish tinge to the cytoplasm
38
Q

What is basophilic stippling? What cell is it seen in?

A
  • punctate basophilia seen in reticulocytes associated with some anemias
  • due to residual ribosomal RNA, but the RNA is degenerate and stains deeply with Wright stain.
39
Q

Reticulocyte

- Lifespan?

A
  • cell typically remains a polychromatic erythrocyte for about 3 days
40
Q

How long does it take to go from a PNB to a reticulocyte?

A
  • span is about 5 days
41
Q

How many RBCs can one PNB give rise to?

A
  • typically 16, but can give up to as many as 32 if stressed
42
Q

Erythrocyte

  • Nucleus?
  • Cytoplasmic features?
A
  • Nuclear - none
  • Cytoplasmic features – biconcave 7-8 µ
    salmon pink color
43
Q

Erythrocyte

  • Location in body?
  • Lifespan?
A
  • remains active in circulation for 120 days
44
Q

Erythrocyte

- Cellular activity?

A
  • interior of the erythrocyte contains mostly hemoglobin, the oxygen-carrying component
45
Q

Erythrocyte

  • What shape is the cell?
  • Why is it that shape?
A
  • biconcave shape
  • hemoglobin molecules that are toward the center of the cell are not distant from the membrane and are able to exchange oxygen.
46
Q

Erythrokinetics

- definition

A
  • dynamics of RBC production and destruction.
47
Q

Erythron

- definition

A
  • collection of all stages of erythrocytes throughout the body: the developing precursors in the bone marrow and the circulating erythrocytes in the peripheral blood and the vascular spaces within specific organs such as the spleen.
48
Q

Red Cell Mass

- definition

A
  • cells in circulation
49
Q

What controls production of EPO?

A
  • oxygen availability
50
Q

What cells produce EPO?

A
  • Hypoxia, too little tissue oxygen, is detected by the peritubular cells, which produce erythropoietin (EPO), the major stimulatory cytokine for RBCs.
51
Q

What organ(s) produce EPO? What organ(s) does it act on?

A
  • production mainly by the kidney, liver can release

- acts on the bone marrow

52
Q

What is signal transduction?

A
  • the process by which the growth factor (cytokine) initiates an intracellular message to the developing RBCs
53
Q

Erythropoietin (EPO)

- Structure?

A
  • glycoprotein 34 kD in size
  • consists of acarbohydrate unitthat reacts specifically with RBC receptors and aterminal sialic acid unit,which is necessary for biological activity
54
Q

Erythropoietin (EPO)

- Define shift reticulocyte.

A
  • Early release of reticulocytes from bone marrow
55
Q

Erythropoietin (EPO)

- Theraputic uses?

A
  • to stimulate RBC production in patients with anemia
56
Q

Microenvironment of the Bone Marrow

- Location of erythropoiesis?

A
  • occurs in what are allederythroid islands
57
Q

Microenvironment of the Bone Marrow

- Site of macrophages?

A
  • surrounded by erythroid precursors in various stages of development.
58
Q

Microenvironment of the Bone Marrow

- What are the three components of the anchoring system?

A
  • a stable matrix of accessory and stromal cells to which normoblasts can attach,
  • bridging (adhesive) molecules for that attachment, and
  • receptors on the erythrocyte membrane
59
Q

Erythrocyte Destruction

  • Describe Macrophage-mediated (extravascular) hemolysis
    • where does it occur?
    • what processes do the RBCs go through?
  • what percentage of the cells die this way?
A
  • Large volume of blood is in spleen, which is stressful on cells due to sluggish movement and lack of glucose
  • RBCs lose flexibility, become spherical and are engulfed by macrophages.
  • Most RBC death occurs this way (90%)
60
Q

Erythrocyte Destruction

  • Describe Mechanical (intravascular) hemolysis
  • what percentage of the cells die this way?
    • what processes do the RBCs go through?
A
  • About 10% normally occurs this way

- Cells lyse within blood vessels from mechanical or traumatic causes