Erythrocyte Production and Destruction Flashcards
The________ has one true function: to carry oxygen from the lung to the tissues, where the oxygen is re-leased.
This is accomplished by the attachment of the oxygen to______, the major cytoplasmic component of mature RBCs.
The role of the RBC in returning_____ to the lungs and_____ the pH of the blood is important but is quite secondary to its oxygen-carrying function.
erythrocyte
hemoglobin
carbon dioxide
buffering
The mammalian erythrocyte is unique among animal cells in that in its mature, functional state, it does not have a______.
nucleus
Although amphibians and birds possess RBCs, their nonmam-malian RBCs retain the_____ throughout the cells’ lives. The implications of this unique mammalian adaptation are significant for cell function and life span.
nuclei
RBCs are formally called_______. Nucleated RBC precursors, normally restricted to the bone marrow, are called_______.
They also may be called______, which refers to developing nucleated RBC precursors (i.e., blasts) with normal appearance.
erythrocytes
erythro-blasts
normoblasts
Three nomenclatures are used for naming erythroid precursors.
The______ terminology is commonly used in the United States and is descriptive of the appearance of the cells.
Some prefer the______ terminology because it parallels the nomenclature used for granulocyte development.
The_______ terminology is used primarily in Europe.
normoblastic
rubriblast
erythroblast
Erythroid Progenitors
The morphologically identifiable erythrocyte precursors develop from two progenitors,______ and _______, both committed to the erythroid cell line.
These erythroid progenitors are named for their ability to form colonies on semisolid media in culture experiments that enable the study of their characteristics and development.
burst-forming unit-erythroid BFU-E) and colony-forming unit-erythroid (CFU-E)
The earliest committed progenitor,_______, gives rise to large colonies because they are capable of multisubunit colonies (called bursts), whereas______ gives rise to smaller colonies.
BFU-E
CFU-E
Estimates of time spent at each stage suggest that it takes about_______ for the BFU-E to mature to the CFU-E and another week for the CFU-E to become a_______, which is the first morphologically identifiable RBC precursor.
While at the CFU-E stage, the cell completes approximately______ divisions before maturing further.
As seen later, it takes approximately another ______for the precursors to become mature enough to enter the circulation, so approximately ______days are required to produce a mature RBC from the BFU-E.
1 week
pronormoblast
three to five
6 to 7 days
18 to 21
Erythroid Precursors
________proliferation, similar to the proliferation of other cell lines, is a process encompassing replication (i.e., division) to increase cell numbers and development from immature to mature cell stages.
Normoblastic
The earliest morphologically recognizable erythrocyte precursor, the________, is derived via the BFU-E and CFU-E from pluripotent hematopoietic stem cells.
It is able to divide, with each daughter cell maturing to the next stage of development, the______
Each of these cells can divide, with each of its daughter cells maturing to the next stage, the_______
Each of these cells also can divide and mature.
pronormoblast
basophilic normoblast
polychromatic normoblast.
In the erythrocyte cell line, there are typically______ and occasionally as many as_____ divisions’ with subsequent nuclear and cytoplasmic maturation of the daughter cells;
from a single pronormoblast, therefore,_____ to ____ mature RBCs usually result.
The changes and cellular activities at each stage described here occur in an orderly and sequential erythroid developmental process.
three/ five
8 to 32
Normoblastic
Pronormoblast
Basophilic normoblast
Polychromatic normoblast
Orthochromic normoblast
Polychromatic erythrocyte
Erythrocyte
Rubriblastic
Rubriblast
Prorubricyte
Rubricyte
Metarubricyte
Polychromatic erythrocyte
Erythrocyte
Erythroblastic
Proerythroblast
Basophilic erythroblast
Polychromatic erythroblast
Orthochromic ervthroblast
Polychromatic erythrocyte
Erythrocyte
Morphologic identification of blood cells depends on a well-stained peripheral blood film or bone marrow smear . In hematology, a_______ stain, such as_____ or _______, is commonly used.
modified Romanowsky
Wright or Wright-Giemsa
The stage of maturation of any blood cell is determined by careful examination of the _____ and _____
The most important features in the identification of RBCs are the_______ (texture, density, homogeneity),______,_______, presence or absence of_____, and_____ color.
nucleus and the cytoplasm.
nuclear chromatin pattern
nuclear diameter
nucleus-to-cytoplasm (N:C) ratio
nucleoli
cytoplasmic
As erythroid precursors mature, several general trends affect their appearance.
- Overall diameter of the cell decreases.
- Diameter of the nucleus decreases more rapidly than does the diameter of the cell. As a result, the N:C ratio also decreases.
- Nuclear chromatin pattern becomes coarser, clumped, and condensed.
- Nucleoli disappear.
- Cytoplasm changes from blue to gray-blue to salmon pink.
The nuclear chromatin of erythroid precursors is inherently coarser than that of_______ precursors.
It becomes even coarser and more clumped as the cell matures, developing a_____-like appearance, in which the dark staining of the chromatin is distinct from the almost white appearance of the parachromatin.
This chromatin/ parachromatin distinction is more dramatic than in other cell lines.
Ultimately the nucleus becomes quite condensed, with no parachromatin evident at all, and the nucleus is said to be______.
myeloid
raspberry
pyknotic
The________ is a morphologic feature used to identify and stage red blood cell and white blood cell precursors.
The ratio is a visual estimate of the area of the cell occupied by the nucleus compared with that of the cytoplasm.
If the areas of each are approximately equal, the N:C ratio is 1:1. Although not mathematically proper, it is common for ratios other than 1:1 to be referred to as if they were fractions.
If the nucleus takes up less than 50% of the area of the cell, the proportion of nucleus is lower and the ratio is lower (e.g., 1:5 or less than 1).
If the nucleus takes up more than 50% of the area of the cell, the ratio is higher (e.g., 3:1 or 3). In the red blood cell line, the proportion of nucleus shrinks as the cell matures and the cytoplasm increases proportionately, although the overall cell diameter grows smaller.
In short, the
N:C ratio decreases.
nucleus-to-cytoplasm (N:C) ratio
_______represent areas where the ribosomes are formed and are seen early in cell development as cells begin actively synthesizing proteins.
As erythroid precursors mature, it disappear, which precedes the ultimate cessation of______.
Nucleoli
protein synthesis
________is due to acidic components that attract basic stains, such as methylene blue. The degree of cytoplasmic basophilia correlates with the amount of______
Blueness or basophilia
ribosomal RNA
The ribosomes and other organelles decline over the life of the developing erythroid precursor, and the blueness fades. Pinkness, called eosinophilia or acidophilia, is due to accumulation of more basic components that attract acid stains, such as______.
eosin
Eosinophilia of erythrocyte cytoplasm correlates with the accumulation of_______ as the cell matures.
Thus the cell starts out being active in_____ production on the ribosomes that make the cytoplasm basophilic, transitions through a period in which the red of_____ begins to mix with that blue, and ultimately ends with a thoroughly _______when the ribosomes are gone and only hemoglobin remains.
hemoglobin
protein
hemoglobin
salmon pink color
General Trends Affecting the Morphology of Erythroid Precursors During the Developmental Process.
(A), Cell diameter_____ and cytoplasm changes from_____ to ____.
(B), Nuclear diameter_____ and color changes from_____ to _____.
(C), Nuclear chromatin becomes ________.
(D), Composite of changes during the developmental process
decreases; blue to salmon pink
decreases; purplish-red to a very dark purple-blue
coarser, clumped, and condensed
Nucleus.
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 open and contains few, if any, fine clumps.
Pronormoblast (Rubriblast)
Cytoplasm.
The cytoplasm is dark blue because of the concentration of ribosomes and RNA.
The Golgi complex may be visible next to the nucleus as a pale, unstained area.
It may show small tufts of irregular cytoplasm along the periphery of the membrane.
Pronormoblast (Rubriblast)
The ________ undergoes mitosis and gives rise to two daughter pronormoblasts.
More than one division is possible before maturation into basophilic normoblasts.
Pronormoblast (Rubriblast)
Location. The pronormoblast is present only in the _____in healthy states.
bone marrow
Cellular activity.
The______ begins to accumulate the components necessary for hemoglobin production.
pronormoblast
The proteins and enzymes necessary for iron uptake and protoporphyrin synthesis are produced.
Globin production begins.
Pronormoblast
Pronormoblast
Length of time in this stage. This stage lasts slightly more than_____
24 hours
Nucleus.
The chromatin begins to condense, revealing clumps along the periphery of the nuclear membrane and a few in the interior.
As the chromatin condenses, the ¥parachromatin areas become larger and sharper,*
Basophilic normoblast (Prorubricyte)
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.
Basophilic normoblast (Prorubricyte)
Cytoplasm. When stained, the cytoplasm may be a deeper, richer blue than in the pronormoblast, hence the name ..
Basophilic normoblast
Division.
The _______undergoes mitosis, giving rise to two daughter cells.
More than one division is possible before the daughter cells mature into polychromatic normoblasts.
basophilic normoblast
Location. The basophilic normoblast is present only in the_____ in healthy states.
bone marrow
Cellular activity.
Detectable hemoglobin synthesis occurs, but the many cytoplasmic organelles, including ribosomes and a substantial amount of messenger ribonucleic acid (mRNA; chiefly for hemoglobin production), completely mask the minute amount of hemoglobin pigmentation.
Basophilic normoblast
Basophilic normoblast
Length of time in this stage. This stage lasts slightly more than______
24 hours
Nucleus.
The chromatin pattern varies during this stage of development, showing some openness early in the stage but becoming condensed by the end.
Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
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.
Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
Cytoplasm.
This is the 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.
Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
The color produced is a mixture of pink and blue, resulting in a murky gray-blue.
The stage’s name refers to this combination of multiple colors, because polychromatophilic means “many color loving.”
Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
Division.
This is the last stage in which the cell is capable of undergoing mitosis, although likely only early in the stage.
It goes through mitosis, producing daughter cells that mature and develop into orthochromic normoblasts.
Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
Location.
The polychromatic normoblast is present only in the_____ in healthy states.
bone marrow
Cellular activity.
Hemoglobin synthesis increases, and the accumulation begins to be visible as a pinkish color in the cytoplasm.
Cellular RNA and organelles are still present, particularly ribosomes, which contribute a blue color to the cytoplasm.
The progressive condensation of the nucleus and disappearance of nucleoli are evidence of progressive decline in transcription of deoxyribonucleic acid (DNA).
polychromatic normoblast
polychromatic normoblast
Length of time in this stage. This stage lasts approximately______
30 hours.
Nucleus.
The nucleus is completely condensed (i.e., pyknotic) or nearly so.
As a result, the N:C ratio is low or approximately 1:2.
Orthochromic Normoblast (Metarubricyte)
Cytoplasm.
The increase in the salmon pink color of the cytoplasm reflects nearly complete hemoglobin production.
The residual ribosomes and RNA 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 RNA and organelles are degraded.
Orthochromic Normoblast (Metarubricyte)
Division.
It is not capable of division because of the condensation of the chromatin.
Orthochromic Normoblast (Metarubricyte)
Location.
The orthochromic normoblast is present only in the_____ in healthy states.
bone marrow
Cellular activity.
Hemoglobin production continues on the remaining ribosomes using messenger RNA produced earlier.
Late in this stage, the nucleus is ejected from the cell.
The nucleus moves to the cell membrane and into a pseudopod-like projection.
Orthochromic Normoblast (Metarubricyte)
Orthochromic Normoblast (Metarubricyte)
As part of the maturation process, loss of______, a protein responsible for holding organelles in proper location in the cytoplasm, is probably important in the movement of the nucleus to the cell periphery.
vimentin
Orthochromic Normoblast (Metarubricyte)
Ultimately the nucleus-containing projection separates from the cell by having the membrane seal and pinch off the projection with the nucleus enveloped by cell membrane.
Nonmuscle myosin of the membrane is important in this pinching process.”
The enveloped extruded nucleus, called a_______ is then engulfed by______
pyrenocyte
bone marrow macrophages.
The macrophages recognize_________ on the pyrenocyte surface as an “eat me” flag.
Other organelles are extruded and ingested in similar fashion.
Often, small fragments of nucleus are left behind if the projection is pinched off before the entire nucleus is enveloped.
These fragments are called _________ when seen in peripheral RBCs and are typically removed from the cells by the splenic macrophage pitting process once the cell enters the circulation.
phosphatidylserine
Howell-Jolly bodies
Orthochromic Normoblast (Metarubricyte)
Length of time in this stage. This stage lasts approximately______
48 hours
Nucleus.
Beginning at the ________ stage, there is no nucleus.
It is a good example of the prior statement that a cell may not have all the classic features described but may be staged by the majority of features.
In particular, when a cell loses its nucleus, regardless of cytoplasmic appearance, it is a _______
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocyte
Cytoplasm.
The cytoplasm can be compared with that of the late orthochromic normoblast in that the predominant color is that of hemoglobin yet with a bluish tinge due to some residual ribosomes and RNA.
By the end of the 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 in electron micrographs
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocvte
Division.
Lacking a nucleus, the it cannot divide.
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocvte
Location.
The polychromatic erythrocyte resides in the bone marrow for about______and then moves into the peripheral blood for about______ before reaching maturity.
During the first several days after exiting the marrow, the polychromatic erythrocyte is retained in the______ for_____ of inclusions and membrane polishing by________, which results in the biconcave discoid mature RBC.
1 to 2 days
1 day
spleen
pitting
splenic macrophages
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocvte
Length of time in this stage.
The cell typically remains a polychromatic erythrocyte for about_____days, with
the first 2 days spent in the______ and the third spent in the_____, although possibly sequestered in the_____.
3
bone marrow
peripheral blood
spleen
Cellular activity.
The polychromatic erythrocyte completes production of hemoglobin from a small amount of residual messenger RNA using the remaining ribosomes.
The cytoplasmic protein production machinery is simultaneously being dismantled.
________, in particular, digests the ribo-somes. The acidic components that attract the basophilic stain decline during this stage to the point that the polychromato-philia is only slightly evident in the polychromatic erythrocytes on a peripheral blood film stained with Wright stain.
Endoribonuclease
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocvte
A small amount of residual ribosomal RNA is present, however, and can be visualized with a______ such as new methylene blue, so called because the cells are stained while alive in suspension (i.e., vital), before the blood film is made
vital stain
Polychromatic (Polychromatophilic) Erythrocyte or Reticulocyte
The residual ribosomes appear as a mesh of small blue strands, a reticulum, or, when more fully digested, merely blue dots.
When so stained, the polychromatic erythrocyte is called a______.
However, the name is often used to refer to the stage immediately preceding the mature erythrocyte,
reticulocyte
The_______ of a polychromatic erythrocyte (reticulocyte) is not seen using Wright stain; however, the residual RNA imparts a bluish tinge to the cytoplasm.
reticulum
Based on the Wright-stained appearance, the reticulocyte is called a _________ because it lacks a nucleus and is no longer an erythroblast but still has a bluish tinge.
polychromatic erythrocyte
When polychromatic erythrocytes are prominent on a peripheral blood film, the examiner uses the comment_______ or _______.
polychro-masia or polychromatophilia
Wright-stained polychromatic erythrocytes are also called_______ for their regular bluish tinge.
This term distinguishes polychromatic erythrocytes from red blood cells with punctate ba-sophilia, in which the blue appears in distinct dots throughout the cytoplasm.
diffusely basophilic erythrocytes
More commonly known as______, punctate basophilia is associated with some anemias.
Similar to the basophilia of polychromatic erythrocytes, punctate basophilia is due to residual ribosomal
RNA, but the RNA is degenerate and stains deeply with Wright stain.
basophilic stippling
Nucleus.
No nucleus is present in mature RBCS.
Erythrocyte
Erythrocyte
Cytoplasm.
The mature circulating erythrocyte is a biconcave disc measuring______ in diameter, with a thickness of about_______.
On a Wright-stained blood film, it appears as a salmon-pink stained cell with a central pale area that corresponds to the concavity.
The central pallor is about _____the diameter of the cell.
7 to 8 mm
1.5 to 2.5 mm
one-third
T or F
Division.
The erythrocyte cannot divide.
True
Location and length of time in this stage.
Mature RBCs remain active in the circulation for approximately_____ days.”
Aging leads to their removal by the_____ as described subsequently.
120
spleen
Cellular activity.
The mature erythrocyte delivers oxygen to tissues, releases it, and returns to the lung to be reoxygenated.
The interior of the erythrocyte contains mostly_______, the oxy-gen-carrying component.
It has a surface area-to-volume ratio and shape that enable optimal gas exchange to occur.
If the cell was spherical, it would have hemoglobin at the center of the cell that would be relatively distant from the membrane and would not be readily oxygenated and deoxygenated.
With the biconcave shape, even hemoglobin molecules that are toward the center of the cell are not distant from the membrane and are able to exchange oxygen.
hemoglobin
