33 Structure and Composition of the Erythrocyte

Question 1

The erythroid progenitors:

Answer 1

• Burst-forming unit–erythroid (BFU-E)
• Colony-forming unit–erythroid (CFU-E)

Question 2

The first morphologically recognizable erythroid precursor cell in the marrow

Answer 2

Proerythroblast

Undergoes in large part 5 mitoses (range 4–6) before maturation to an orthochromatic erythroblast

Question 3

Two forms of erythroid differentiation:

Answer 3

• Primitive
• Definitive

Question 4

The hallmark of primitive erythron

Answer 4

Release of nucleated erythroid precursors containing embryonic hemoglobin

Question 5

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

Answer 5

Primitive erythron

Question 6

Predominates during the remainder of fetal development and is the only type of erythroid maturation present through childhood and adult life

Answer 6

Definitive erythron

Question 7

The definitive stage of maturation makes its appearance around __________ of embryogenesis

Answer 7

Week 5

When multipotential stem cells develop and seed the liver, which maintains the erythron for most of fetal life

Question 8

All normal human erythropoiesis occurs in the marrow in the form of

Answer 8

Erythroblastic islands

Centrally located macrophage surrounded by maturing terminally differentiating erythroid cells

Question 9

The earliest identifiable progenitor committed to the erythroid lineage

Answer 9

Burst-Forming Unit–Erythroid (BFU-E)

Question 10

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

Answer 10

Colony-Forming Unit–Erythroid

Question 11

Five stages of erythroblast development

Answer 11

• Proerythroblasts
• Basophilic erythroblast
• Polychromatophilic erythroblasts
• Orthochromic normoblast
• Late orthochromatic erythroblasts

Question 12

• Large cell, irregularly rounded or slightly oval
• Nucleus occupies approximately 80% of the cell area and contains fine chromatin delicately distributed in small clumps

Answer 12

Proerythroblasts

Question 13

• 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

Answer 13

Basophilic Erythroblasts

Question 14

• 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

Answer 14

Polychromatophilic Erythroblasts

Question 15

• 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

Answer 15

Orthochromic (syn. Orthochromatic) Erythroblasts

Question 16

All normal erythroblasts are sideroblasts in that they contain iron in structures called

Essential for the transfer of iron for heme (hemoglobin) synthesis

Answer 16

Siderosomes

Question 17

Staining for iron stores

Answer 17

Prussian blue

A minority of normal erythroblasts (approximately 15–20 %) can be identified as containing siderosomes

Question 18

2 types of pathologic sideroblasts

Answer 18

• 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)

Question 19

Maturation of the reticulocyte requires _____ hours

Answer 19

48 to 72 hours

Question 20

Are released into the circulation during an intense erythropoietin response to acute anemia or experimentally in response to large doses of exogenously administered erythropoietin

Answer 20

“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.

Question 21

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

Answer 21

Howell-Jolly Bodies

Question 22

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.

Answer 22

Pocked (or Pitted) Red Cells

Question 23

The ringlike or figure-of-eight structures sometimes seen in megaloblastic anemia within reticulocytes and in an occasional, heavily stippled, late-intermediate megaloblast

Answer 23

Cabot Rings

Question 24

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

Answer 24

Basophilic Stippling

Question 25

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**

Answer 25

Heinz Bodies

Question 26

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**

Answer 26

Hemoglobin H Inclusions

Question 27

**Iron granulations** are larger and more numerous in the pathologic state May contain degenerating **mitochondria**, **ribosomes**, and other cellular remnants.

Answer 27

Siderosomes and Pappenheimer Bodies ## Footnote **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**

Question 28

The normal resting shape of the erythrocyte is a

Answer 28

Biconcave disc

Question 29

Normal RBC Diameter: Average volume: Surface area:

Answer 29

Diameter: 7 to 8 μm Average volume: 90 fL Surface area: 140 μm ## Footnote 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.

Question 30

During its ________ -day life span, the red cell travels approximately ____ km and loses approximately ____ % of its cell surface area.

Answer 30

100- to 120-day 250 km 15 to 20%

Question 31

The resiliency and fluidity of the membrane to deformation is regulated by the ________________

Answer 31

Spectrin-based membrane skeleton

Question 32

Red cell deformability is influenced by three distinct cellular components:

Answer 32

* (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

Question 33

A ___ % reduction in surface area results in rapid removal of red cells by the human spleen.

Answer 33

17%

Question 34

A very good marker of cell age

Answer 34

Glycated hemoglobin ## Footnote The densest 1% of circulating red cells are the most aged—they have the highest levels of glycated hemoglobin

Question 35

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

Answer 35

Spherocytes

Question 36

Are seen in hereditary stomatocytosis, as well as in hereditary spherocytosis, alcoholism, cirrhosis, obstructive liver disease, and erythrocyte sodium pump defects

Answer 36

Stomatocytes

Question 37

Are seen in hereditary elliptocytosis as well as in thalassemia, iron deficiency, and megaloblastic anemia

Answer 37

Elliptocytes

Question 38

In blood films of normal subjects, elliptical or oval cells usually constitute _________ % of the erythrocytes.

Answer 38

less than 1%

Question 39

Has irregularly shaped, with 2 to 10 hemispherically tipped spicules of variable length and diameter Seen in neuroacanthocytosis and in abetalipoproteinemia

Answer 39

Acanthocytes

Question 40

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.

Answer 40

Target Cells (Codocytes) ## Footnote Target red cells are osmotically resistant

Question 41

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.

Answer 41

Sickle Cells (Drepanocytes) ## Footnote 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

Question 42

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

Answer 42

Fragmented Cells (Schistocytes)