Erythropoiesis Flashcards
Erythropoiesis
Process of RBC formation inside the bone marrow
Erythron
Total mass of RBCs in peripheral blood and bone marrow RBC precursors
RBC mass
Erythrocytes in the circulation
Erythrokinetics
Dynamics of RBC creation and destruction (average lifespan 120 days)
Ineffective erythropoiesis
Production of defective RBC precursors, often undergoing apoptosis in bone marrow
Examples of ineffective erythropoiesis conditions
Vitamin B12 deficiency, folate deficiency, thalassemia, sideroblastic anemia
Insufficient erythropoiesis
Decrease in RBC precursors, leading to decreased RBC production
Examples of insufficient erythropoiesis conditions
Iron deficiency, renal disease, acute leukemia
RBC survival test method
Label RBCs with chromium-51 (51Cr), track radioactivity decay to calculate survival time
Normal RBC survival time range
28 to 38 days
Anemia is classifies as
A sign, not a disease
Immature hematopoietic cells committed to a cell line; cannot be identified
Progenitor cells
Immature hematopoietic cells identifiable as belonging to a specific cell line
Precursor cells
Earliest marker of erythroid differentiation
CD71 (transferrin receptor)
Transport protein of iron in blood
Transferrin
Primary cell source of erythropoietin (EPO)
Peritubular interstitial cells in kidneys
Primary target cells of EPO
BFU-E and CFU-E
Effects of EPO
1) Early release of reticulocytes from bone marrow, 2) Reduces maturation time in bone marrow, 3) Prevents apoptosis (major way EPO increases RBC mass)
Therapeutic applications of EPO
Anemia of chronic renal disease, autologous blood donation, anemia in HIV infection
“Blood doping”
Athletes use EPO injections to increase oxygen-carrying capacity, which can lead to thrombosis
Growth hormone and erythropoiesis
Stimulates erythropoiesis, produced by pituitary gland
Testosterone and erythropoiesis
Stimulates erythropoiesis, produced by testes
Prolactin and erythropoiesis
Stimulates erythropoiesis, produced by pituitary gland
Estrogen and erythropoiesis
Inhibits erythropoiesis, produced by ovaries
Stages of RBC maturation
BFU-E → CFU-E → Rubriblast → Pro(basophilic) → rubriblast (polychromatophilic) → Meta(Orthochromatic) → Reticulocyte → Mature erythrocyte
Rubriblastic stages
Rubriblast → Prorubricyte → Rubricyte → Metarubricyte → Reticulocyte (seen in supravital stain) → Mature erythrocyte
Normoblastic stages
Pronormoblast → Basophilic (Early) Normoblast → Polychromatophilic/Intermediate Normoblast → Orthochromatic Normoblast (Late Normoblast) → Reticulocyte → Mature erythrocyte
Erythroblastic stages
Proerythroblast → Basophilic (Early) Erythroblast → Polychromatophilic Erythroblast (Intermediate Erythroblast) → Orthochromatic Erythroblast → Reticulocyte → Mature erythrocyte
Earliest committed erythroid progenitor
BFU-E (Burst forming unit- erythroid)
Second committed erythroid progenitor
CFU-E (Colony forming unit erythroid)
Time from BFU-E to CFU-E
1 week
Time from CFU-E to Rubriblast
1 week
Time for BFU-E to mature to erythrocyte
18 to 21 days
Time spent as recognizable precursors in bone marrow
Approximately 6 days
Supravital stains for reticulocytes
BCB (Brilliant cresyl blue), NMB (New methylene blue)
Reticulocytes under Wright stain
Polychromatophilic erythrocytes, Diffusely basophilic erythrocytes
Changes in erythroid precursors during maturation
Decrease in diameter, nuclear diameter decreases, chromatin becomes coarser, nucleoli disappear, cytoplasm changes from blue to salmon pink
N:C ratio definition
Nucleus to cytoplasm ratio, used to identify and stage RBC and WBC precursors
What does N:C ratio represent?
Visual estimate of nucleus and cytoplasm area in a cell
N:C ratio of 1:1
Nucleus and cytoplasm occupy approximately equal areas
N:C ratio <1:1
Nucleus occupies less than 50% of the cell area
N:C ratio >1:1
Nucleus occupies more than 50% of the cell area
What causes basophilia in cells?
Acidic components attracting basic stains (e.g., methylene blue)
What does the degree of basophilia correlate with?
Quantity of ribosomal RNA in the cell
What causes eosinophilia (acidophilia) in cells?
Accumulation of basic components attracting eosin (acid stain)
What does the degree of eosinophilia correlate with in RBCs?
Accumulation of hemoglobin as RBCs mature
What is the size of a Rubriblast (Pronormoblast)?
12 to 19 μm
What is the N:C ratio for Rubriblast (Pronormoblast)?
4:1 (Turgeon), 8:1 (Rodak)
What are key characteristics of Rubriblast (Pronormoblast)?
!! earliest recognizable erythroid precursor under a light microscope; Round or slightly oval nucleus, 1-2 nucleoli, dark blue cytoplasm due to ribosomes, smallest cytoplasm,
What does Rubriblast (Pronormoblast) give rise to?
Two prorubricytes
What is the size of a Prorubricyte (Basophilic Normoblast)?
12 to 17 μm
What is the N:C ratio for Prorubricyte (Basophilic Normoblast)?
4:1 (Turgeon), 6:1 (Rodak)
What are key characteristics of Prorubricyte (Basophilic Normoblast)?
carse chromatin, absence of nucleoli, last stage with nucleolus
What does Prorubricyte (Basophilic Normoblast) give rise to?
Four rubricytes
What is the first stage of hemoglobin synthesis in erythropoiesis?
Prorubricyte (Basophilic Normoblast)
What is the size of a Rubricyte (Polychromatic Normoblast)?
11 to 15 μm
What is the N:C ratio for Rubricyte (Polychromatic Normoblast)?
‘1:1
What are key characteristics of Rubricyte (Polychromatic Normoblast)?
Round, smaller nucleus with a thick membrane, eccentric, no nucleolus, gray cytoplasm
What does Rubricyte (Polychromatic Normoblast) give rise to?
Two metarubricytes
What is the last stage for mitosis in erythropoiesis?
Rubricyte (Polychromatic Normoblast)
What is the first stage where cytoplasm becomes pink in erythropoiesis?
Rubricyte (Polychromatic Normoblast)
What is the difference in the nucleus between a Rubricyte and a Lymphocyte?
Rubricyte nucleus: checkerboard, Lymphocyte nucleus: crushed velvet
What is the difference in cytoplasm color between a Rubricyte and a Lymphocyte?
Rubricyte cytoplasm: muddy/gray, Lymphocyte cytoplasm: sky blue or robin egg blue
What is the size of a Metarubricyte (Orthochromatic Normoblast)?
8 to 12 μm
What is the N:C ratio for Metarubricyte (Orthochromatic Normoblast)?
‘1:2
What are key characteristics of Metarubricyte (Orthochromatic Normoblast)?
Pyknotic nucleus, no nucleolus, salmon-pink cytoplasm
What happens to the nucleus at the Metarubricyte stage?
Nucleus is extruded and the cell becomes a reticulocyte
What are other names for Metarubricyte (Orthochromatic Normoblast)?
Nucleated RBC (NRBC), Pyknotic erythroblast, Acidophilic normoblast
What is the last stage with a nucleus in erythropoiesis?
Metarubricyte (Orthochromatic Normoblast)
What is a Pyrenocyte?
Enveloped extruded nucleus, engulfed by bone marrow macrophages
What are Howell-Jolly bodies?
Small fragments of nucleus left behind after projection pinching, seen in RBCs in circulation
What happens to Howell-Jolly bodies in circulation?
They are typically removed by splenic macrophages through pitting process
What is the size of a Reticulocyte?
7 to 10 μm
What is the predominant color of Reticulocyte cytoplasm?
Hemoglobin color with a bluish tinge due to residual ribosomes and RNA
What happens to the Reticulocyte by the end of its stage?
It becomes salmon pink
What is the last stage of hemoglobin synthesis?
Reticulocyte
What are Reticulocytes?
Young RBCs with residual RNA, the last immature erythrocyte stage
How long does a Reticulocyte spend in the bone marrow and peripheral blood?
2 to 3 days in bone marrow and 1 day in peripheral blood
What is the shape of a Reticulocyte in electron micrographs?
Irregular shape
What is the size of a Mature Erythrocyte?
6 to 8 μm
What is the color of a Mature Erythrocyte’s cytoplasm?
Salmon pink with a central pallor occupying 1/3 of the cell’s diameter
What is the shape of a Mature Erythrocyte?
Biconcave disk
What is the thickness of a Mature Erythrocyte?
1.5 to 2.5 μm
What is the average life span of a Mature Erythrocyte?
120 days
How many erythrocytes are produced from each rubriblast?
8-32
What is the normal RBC to WBC ratio?
Approximately 600:1
What is the normal RBC to Platelet ratio?
Approximately 15:1
Does an Adult RBC contain mitochondria?
No, it contains no mitochondria