33 Structure and Composition of the Erythrocyte Flashcards
The erythroid progenitors:
- Burst-forming unit–erythroid (BFU-E)
- Colony-forming unit–erythroid (CFU-E)
The first morphologically recognizable erythroid precursor cell in the marrow
Proerythroblast
Undergoes in large part 5 mitoses (range 4–6) before maturation to an orthochromatic erythroblast
Two forms of erythroid differentiation:
- Primitive
- Definitive
The hallmark of primitive erythron
Release of nucleated erythroid precursors containing embryonic hemoglobin
Supplies the embryo with oxygen during the phase of rapid growth before the definitive form of maturation has had a chance to develop and seed an appropriate niche
Primitive erythron
Predominates during the remainder of fetal development and is the only type of erythroid maturation present through childhood and adult life
Definitive erythron
The definitive stage of maturation makes its appearance around __________ of embryogenesis
Week 5
When multipotential stem cells develop and seed the liver, which maintains the erythron for most of fetal life
All normal human erythropoiesis occurs in the marrow in the form of
Erythroblastic islands
Centrally located macrophage surrounded by maturing terminally differentiating erythroid cells
The earliest identifiable progenitor committed to the erythroid lineage
Burst-Forming Unit–Erythroid (BFU-E)
Dependent on erythropoietin for its development and can undergo only a few cell divisions.
Forms a smaller colony of morphologically recognizable erythroid cells in 5 to 7 days
Colony-Forming Unit–Erythroid
Five stages of erythroblast development
- Proerythroblasts
- Basophilic erythroblast
- Polychromatophilic erythroblasts
- Orthochromic normoblast
- Late orthochromatic erythroblasts
- Large cell, irregularly rounded or slightly oval
- Nucleus occupies approximately 80% of the cell area and contains fine chromatin delicately distributed in small clumps
Proerythroblasts
- Nucleus occupies three-fourths of the cell area and is composed of characteristic dark violet heterochromatin interspersed with pink-staining clumps of euchromatin linked by irregular strands
- Wheel spokes or a clock face
- Cytoplasm stains deep blue, leaving a perinuclear halo that expands into a juxtanuclear clear zone around the Golgi apparatus
Basophilic Erythroblasts
- The cytoplasm changes from deep blue to gray as hemoglobin dilutes the polyribosome content
- Nucleus occupies less than half of the cell area
- The nucleolus is lost, but the perinuclear halo persists
- Erythroblasts lose their mitotic potential
Polychromatophilic Erythroblasts
- Nucleus appears almost completely dense and featureless
- Smallest of the erythroblastic series
- Cell movement can be appreciated under the phase-contrast microscope
The cell ultrastructure is characterized by irregular borders, reflecting its motile state
Orthochromic (syn. Orthochromatic) Erythroblasts
All normal erythroblasts are sideroblasts in that they contain iron in structures called
Essential for the transfer of iron for heme (hemoglobin) synthesis
Siderosomes
Staining for iron stores
Prussian blue
A minority of normal erythroblasts (approximately 15–20 %) can be identified as containing siderosomes
2 types of pathologic sideroblasts
- Erythroblast that has an increase in number and size of Prussian blue–stained siderotic granules throughout the cytoplasm.
- Erythroblast that shows iron-containing granules that are arranged in an arc or a complete ring around the nucleus (ring or ringed sideroblasts)
Maturation of the reticulocyte requires _____ hours
48 to 72 hours
Are released into the circulation during an intense erythropoietin response to acute anemia or experimentally in response to large doses of exogenously administered erythropoietin
“Stress” reticulocytes
Macroreticulocytes
These cells may be twice the normal volume, with a corresponding increase in mean cell hemoglobin (MCH) content.
Quantification is commonly performed by applying a fluorescent stain to tag RNA and then dividing reticulocytes into high-, medium-, and low-fluorescence categories using a fluorescence-sensitive flow cytometer.
Are small nuclear remnants that have the color of a pyknotic nucleus on Wright-stained films and show a positive Feulgen reaction for DNA.
Present in the blood of persons who have undergone splenectomy and in patients with megaloblastic anemia, and hyposplenic states
Howell-Jolly Bodies
Have surface membrane “pits” or craters
Begin to rise post-splenectomy, reaching a plateau at 2 to 3 months
Counts are sometimes used as a surrogate test for splenic function.
Pocked (or Pitted) Red Cells
The ringlike or figure-of-eight structures sometimes seen in megaloblastic anemia within reticulocytes and in an occasional, heavily stippled, late-intermediate megaloblast
Cabot Rings
Has punctate basophilia represents aggregated ribosomes
Found in In conditions such as lead intoxication, pyrimidine 5’-nucleotidase deficiency, and thalassemia, the altered reticulocyte ribosomes have a greater propensity to aggregate
Basophilic Stippling
Denatured proteins, primarily hemoglobin stained supravitally with brilliant cresyl blue or crystal violet, that form in red cells as a result of chemical insult
Found in hereditary defects of the hexose monophosphate shunt; in the thalassemias; and in unstable hemoglobin syndromes
Heinz Bodies
Composed of β4 tetramers, indicating that β chains are present in excess as a result of impaired α-chain production
Brilliant cresyl blue causes the formation of a large number of small membrane-bound inclusions, giving the cell a characteristic “golf ball–like” appearance when viewed by light microscopy.
Found in α-thalassemia and in rare patients with primary myelofibrosis
Hemoglobin H Inclusions
Iron granulations are larger and more numerous in the pathologic state
May contain degenerating mitochondria, ribosomes, and other cellular remnants.
Siderosomes and Pappenheimer Bodies
Siderosomes usually are found in the cell periphery, whereas basophilic stippling tends to be distributed homogeneously throughout the cell.
Pappenheimer bodies are siderosomes that stain with Wright stain; confirmed by the presence of acid phosphatase
The normal resting shape of the erythrocyte is a
Biconcave disc
Normal RBC
Diameter:
Average volume:
Surface area:
Diameter: 7 to 8 μm
Average volume: 90 fL
Surface area: 140 μm
Stains reddish-brown with Wright-stained blood films and pink with Giemsa stain.
The central third of the cell appears relatively pale compared with the periphery, reflecting its biconcave shape.
During its ________ -day life span, the red cell travels approximately ____ km and loses approximately ____ % of its cell surface area.
100- to 120-day
250 km
15 to 20%
The resiliency and fluidity of the membrane to deformation is regulated by the ________________
Spectrin-based membrane skeleton
Red cell deformability is influenced by three distinct cellular components:
- (1) cell shape or cell geometry, which determines the ratio of cell surface area to cell volume (SA:V; higher values of SA:V facilitate deformation);
- (2) cytoplasmic viscosity, which is primarily regulated by the mean corpuscular hemoglobin concentration (MCHC) and is therefore influenced by alterations in cell volume;
- (3) membrane deformability and mechanical stability, which are regulated by multiple membrane properties, which include elastic shear modulus, bending modulus, and yield stress
A ___ % reduction in surface area results in rapid removal of red cells by the human spleen.
17%
A very good marker of cell age
Glycated hemoglobin
The densest 1% of circulating red cells are the most aged—they have the highest levels of glycated hemoglobin
Represent red cells, with the most decreased SA:V ratio
Seen in hereditary spherocytosis, immune hemolytic anemia, stored blood, Heinz body hemolytic anemia and caused by cell fragmentation
Spherocytes
Are seen in hereditary stomatocytosis, as well as in hereditary spherocytosis, alcoholism, cirrhosis, obstructive liver disease, and erythrocyte sodium pump defects
Stomatocytes
Are seen in hereditary elliptocytosis as well as in thalassemia, iron deficiency, and megaloblastic anemia
Elliptocytes
In blood films of normal subjects, elliptical or oval
cells usually constitute _________ % of the erythrocytes.
less than 1%
Has irregularly shaped, with 2 to 10 hemispherically tipped spicules of variable length and diameter
Seen in neuroacanthocytosis and in abetalipoproteinemia
Acanthocytes
Results from a relative excess of membrane surface area or decreased cell volume leading to increased SA:V ratio
Seen in obstructive liver disease, hemoglobinopathies (S and C), thalassemia, iron deficiency, postsplenectomy, and lecithin cholesterol acetyltransferase deficiency.
Target Cells (Codocytes)
Target red cells are osmotically resistant
The fusiform cell in the crescent shape with two pointed extremities is encountered most commonly in deoxygenated blood samples as a result of polymerization of sickle hemoglobin.
Sickle Cells (Drepanocytes)
Upon reoxygenation, the sickle cell resumes the discocyte form and, in so doing, can lose membrane by microspherulation and fragmentation during retraction of long spicules
Seen in microangiopathic hemolytic anemias (thrombotic thrombocytopenic purpura [TTP], disseminated intravascular coagulation [DIC], vasculitis, glomerulonephritis, renal graft rejection), carcinomatosis, heart valve hemolysis (prosthetic or pathologic valves), severe burns, and march hemoglobinuria
Fragmented Cells (Schistocytes)
