Erythropoiesis Flashcards
Total mass of RBCs circulating in the peripheral blood and the BM RBC precursors
Erythron
Refers to erythrocytes in the circulation only
RBC mass
Conditions that result to ineffective erythropoiesis
- Vitamin B12 deficiency
- Folate deficiency
- Thalassemia
- Sideroblastic anemia
Type of anemia in Vitamin B12 deficiency and Folate deficiency
Macrocytic, normochromic anemia
Type of anemia in thalassemia and sideroblastic anemia
Microcytic, hypochromic anemia
Anemia in renal disease and acute leukemia
Normocytic, normochromic
Difference between progenitor cells and precursor cells
Precursor cells are morphologically identifiable but progenitor cells are not.
* both are immature hematopoietic cells
Earliest marker of erythroid differentiation
CD71 * Can also act as a transferrin receptor
Chief stimulator cytokines for RBCs
Erythropoietin (EPO)
Primary organ responsible for producing EPO
Kidney
Primary cell source of EPO
Peritubular interstitial cell of the kidneys
Primary target cells of EPO
BFU-E and CFU-E
Hormones that stimulates erythropoiesis directly
Growth hormone and Prolactin (both from Pituitary gland)
Hormones that stimulates erythropoiesis indirectly
Testosterone and Estrogen (From testes and ovaries respectively)
Reason of difference in the RBC count, Hgb, and Hct. of male and female
Hormones (Testosterone) * Testosterone stimulates erythropoiesis indirectly
Committed erythroid progenitor cells
BFU-E and CFU-E
Number of days for a BFU-E to mature to an erythrocyte
18-21 days
Give the Normoblast and Erythroblast nomenclature of rubriblast
Pronormoblast / Proerythroblast
Arrange the order of Erythropoiesis
- Rubriblast
- Prorubricyte
- Rubricyte
- Metarubricyte
- Reticulocyte
- Mature Erythrocyte
N:C ratio of pronormoblast
8:1
Last stage of erythropoiesis with a nucleolus
Prorubricyte
First stage of hemoglobin synthesis
Prorubricyte / Basophilic normoblast
One pronormoblast can produce how many prorubricytes?
2
One prorubricyte can produce how many rubricytes?
4
Stage of erythropoiesis commonly confused as a lymphocyte
Rubricyte (Polychromatic Normoblast)
Cytoplasmic color of rubricytes
Muddy gray
Differentiate lymphocytes and reticulocytes based on the ff. Characteristics:
- Nucleus
- Cytoplasm
Lymphocytes 1. Nucleus: crushed velvet 2. Cytoplasm: Sky blue / Robin egg blue Rubricytes 1. Nucleus : checkerboard 2. Cytoplasm: muddy gray
= muddy gray due to the mixing of blue (basophilic) and pink (acidic) color
Last stage capable of mitosis
Rubricyte (Polychromatophilic Normoblast)
Rubricyte N:C ratio
4:1
Cytoplasmic color of orthrochromatic normoblast/ Metarubricyte
Salmon pink
Nuclear characteristic of orthochromatic normoblast
Pyknotic
–> 1st stage of NO mitotic division
Also known as nucleated RBC / acidophilic normoblast
Metarubricyte
Last erythropoietic stage with a nucleus
Metarubricyte
Important difference:
* last stage with a nucleolus- prorubricyte
Envelope extruded nucleus
Pyrenocyte
–> eaten by macrophage
Fragments of nucleus that may be left behind inside the RBCs
Howell-Jolly bodies
What makes up the Howell Jolly bodies?
Nuclear fragments from RBCs
Last precursor of the RBC
Reticulocyte
Last stage of hemoglobin synthesis
Reticulocyte (Polychromatophilic Erythrocyte)
Two types of reticulocytes
Shift cells and stress reticulocytes
Type of reticulocyte seen in cases of increased RBC production
Shift cells / polychromatic macrocytic cell
Number of erythrocytes produced from each single rubriblast
16
Central pallor contains _ of the cell’s diameter
1/3
Normal ratio of RBCs to WBCs
600:1
Normal ratio of RBCs to platelets
15:1
% of RBC membrane constituents
52% proteins
40% lipids
8% carbohydrates
Primary cytoskeletal proteins of RBC membrane
Alpha- spectrin and beta-spectrin
MCHC value of patients with hereditary spherocytosis
35-38 g/dL
* only disease characterized by high MCHC value
Confirmatory test for hereditary spherocytosis
EMA binding test (eosin-5’-maleimide)
Normal maturation time for reticulocytes in blood
1 day / 24 hrs
Production of reticulocytes / day
50 x 10^9/L/day
Measure of effective erythropoiesis
Reticulocyte count
Immature, non-nucleates RBC which contains >/= 2 blue-stained granulofilamentous materials (reticulum)
Reticulocytes
Stain that demonstrates a reticulocyte
Supravital stain * stains the reticulum
Normal reference range for retic count
0.5-1.5%
First sign of accelerated erythropoiesis
Reticulocytosis aka “Polychromatic / polychromatophilia”
Increase in reticulocyte count:
Decrease in reticulocyte count:
Increase: reticulocytosis
Decrease: reticulocytopenia
Patients condition in reticulocytopenia
Aplastic anemia * BM not capable of producing RBCs
Supravital stain that is most preferred for staining reticulocytes
New methylene blue
Composition of new methylene blue (give the function as well)
- Sodium oxalate - prevents coag.
2. Sodium chloride - provides isotonicity
Name the 2 supravital stains utilized for the demonstration of reticulocytes
- New methylene blue
2. Brilliant cresyl blue
Supravital stain that provides inconsistent staining result but is considered as an alternative to new methylene blue
Brilliant cresyl blue
In the Miller disk method of reticulocyte ct, large square A is used for _
Large square A: counting Reticulocytes
* Small square B: counting RBCs
Minimum no. of RBCs to be counted in the small square B of the Miller disk
112
Indicative of G6PD deficiency
Heinz bodies
As the cell matures, it becomes more acidic/basic?
BASIC
- Nucleic acid - Acidic substance –> Basophilic
- Hemoglobin - Basic substance –> Acidophilic
The first stage of globin production
Pronormoblast
Start of detectable hemoglobin synthesis
Basophilic normoblast / Prorubricyte
The last stage capable of mitosis
Polychromatophilic Normoblast (Rubricyte)
Requirement for Polychromatophilic Erythrocyte
NO NUCLEUS
–> but still has Ribosomes
What produces the hemoglobin?
Mitochondria and Ribosomes
Difference of reticulocyte and basophilic stippling
Both has RNA component
Reticulocyte
–> Supravital stain (cannot be detected by Wright’s)
Basphilic stippling / Punctate Basophilia
–> Wright’s stain –> means ABNORMAL RNA
RNA CANNOT be stained using
Wright’s stain
Prominent reticulocytes in a blood film
Polychromasia
RBCs in circulation and bone marrow
Erythron
RBCs in circulation ONLY
RBC mass
An organ that senses the oxygen level in the blood
Kidneys
- -> EPO
- -> Burr cells
Effects of EPO
- Early release of reticulocytes
- Prevents apoptotic cell death
- Reducing the time needed for cells to mature in BM
Testosterone DIRECTLY stimulates Erythropoiesis while ___ hormones INDIRECTLY affects Erythropoiesis
Thyroid and Pituitary Hormones INDIRECTLY
Reduced iron (without oxygen)
Ferrous (Fe2+)
–> Iron with oxygen –> Ferric (Fe3+)