VII. Erythrocytes

General Characteristics of Erythrocytes:

1. Oxygen ______, removal of metabolic waste

2. ____________ is required for function

3. Normal life span is ________

1. Transport

2. Loss of Nucleus

3.120 Days

Erythropoietin:

1.Produced mainly by _____

2.____________ that stimulates erythrocyte production from _______

1.Kidneys

2.Growth factor, Myeloid progenitor cell

Erythrocyte maturation order:

1. pronormoblast (rubriblast)

2. Basophili normoblast (prorubricyte)

3. Orthohromic normoblast (metarubricyte)

4. Reticuloyte

5. Mature Erythrocyte

Reticulocyte

• No nucleus (mitochondria and ribosomes)

• Last stage in BM before release

• 0.5–1.5% for adults, 2.5–6.5% for newborns (slightly higher at high altitudes)

• Supravital stain

• Best indicators of BM function

• Stress reticulocytes: young cells released from bone marrow

Mature Erthryocyte Stained Smear findings

Wright Stained

• Normal Central Pallor

• If < -» spherocytes: thermal injury and liver disease

• If > 1/3 of the cell diameter → microcytic anemia

RBC ref range

• Females 4.0–5.4 10^12/ (10^6 /mL

• Males 4.6–6.0 10^12/L (10^6 /mL)

Substances Needed for Erythropoiesis

• Iron: Must be in the ferrous state (Fe2+) to transport O2

• Amino acids: Globin-chain synthesis

• Folic acid/vitamin B12: DNA replication/cell division

• Others: Erythropoietin, vitamin B6 (pyridoxine), trace minerals

Normocytes (discocytes)

normal RBCS that are approx. the same size as the nucleus of a small lymphocyte.

Macrocytes

• > 8 um in diameter

• MCV > 100 fL

• Megaloblastic anemia (ex: folate deficiency)

• non-megaloblastic anemia of liver disease

Microcytes

• < than 6 mm in diameter

• MCV less than 80 fL

• Seen in…

  • iron-deficiency anemia

  • thalassemias

  • sideroblastic anemia

  • anemia of chronic disease

Anisocytosis

• Variation in RBC size

  • heterogeneous RBC population (dimorphism)

• RDW > 15%

• Seen in

  • post-transfusion

  • post-treatment for a deficiency (e.g., iron)

  • presence of two concurrent deficiencies (e.g., iron and vitamin B12)

  • idiopathic sideroblastic anemia

Poikilocytosis

variation in shape

Echinocytes: crenated and burr cells

• evenly spaced round projections

  • central pallor area present

• Seen in…

  • liver disease

  • uremia

  • heparin therapy

  • pyruvate kinase deficiency

Acanthocytes (spur cells)

• unevenly spaced pointed projections

• lack a central pallor area

• alcoholic liver disease, post-splenectomy, and abetalipoproteinemia

Target cells (codocytes)

• increased surface-to-volume

  ratio

• Seen in

  • liver disease

  • hemoglobinopathies

  • thalassemia

  • iron-deficiency anemia

Spherocytes

• Smaller volume than normal erythrocyte

• decreased surface-to-volume ratio

• Lack central pallor area

• Associated with red cell membrane protein defects

• MCHC >37%

  • increased osmotic fragility

• Damaged RBC

• seen in…

  • hereditary spherocytosis,

  • G6PD deficiency

  • immune hemolytic anemias

• Microspherocytes (64 mm)

• seen in severe burns

Teardrops (dacryocytes)

• Pear-shaped cell with one blunt projection

• Seen in…

  • megaloblastic anemias, thalassemia

  • extramedullary hematopoiesis (myelofibrosis, myelophthisic anemia)

Sickle cells (drepanocytes)

• thin, elongated, pointed ends, crescent-shaped

  • usually lack central pallor

• Contain polymers of abnormal hemoglobin S

• Seen in hemoglobinopathies SS, SC, SD, and S/β-thalassemia

• cell membrane alterations due to amino acid substitution

Helmet cells (horn cells or keratocytes)

• Interior portion of cell is hollow, resembling a horn or helmet

• Seen in…

  • microangiopathic hemolytic anemias (DIC, HUS, TTP)

  • thermal injury

  • renal transplant rejection

  • G6PD deficiency

Stomatocytes (mouth cells or coin slot)

• Characterized by an elongated or slit-like area of central pallor

• Seen in…

  • liver disease

  • hereditary stomatocytosis

Elliptocytes (ovalocytes)

• Cigar- to egg-shaped erythrocytes

• Associated with defects of the red cell membrane proteins

• Seen in…

  • hereditary elliptocytosis

  • iron-deficiency anemia (pencil forms)

  • megaloblastic anemia (macro-ovalocytes)

  • thalassemia major

Erythrocyte Inclusions

1. Nucleated RBCs (nRBCs, nucRBCs)

2. Howell-Jolly bodies

3. Basophilic stippling

4. Pappenheimer bodies

5. Cabot rings

6. Hemoglobin C crystals

7. Hemoglobin SC crystals (Washington monument)

8. Heinz bodies

9. Malarial parasites

Nucleated RBCs (nRBCs, nucRBCs)

• Usually orthochromic normoblasts (metarubricyte)

• BM stimulation or ↑ erythropoiesis

• Associated w/ thalassemia major, sickle cell anemia, and other hemolytic

  anemias, erythroleukemia, and myeloproliferative disorders

• none on a PBS

Howell-Jolly bodies

• DNA fragments, usually one per cell

• Stain dark purple to black with Wright stain

  c. not normal → pitted by splenic macrophages

  d. Seen in sickle cell anemia, beta-thalassemia major, and other severe hemolytic anemias, megaloblastic anemia, alcoholism, post-splenectomy

Basophilic stippling

• Multiple, tiny, fine, or coarse inclusions (ribosomal RNA remnants)

• dispersed throughout the cell

  b. Stain dark blue with Wright stain

  c. Seen in thalassemias, megaloblastic anemias, sideroblastic anemia, lead

  poisoning, and alcoholism

Pappenheimer bodies

• Small, irregular, dark-staining iron granules usually clumped together at

  periphery of the cell

• Prussian blue stain

  • dark violet w/ Wright

    stain

• Seen in sideroblastic anemia, hemoglobinopathies, thalassemia, megaloblastic anemia, myelodysplastic syndrome (RARS)

Cabot Rings

• Thin, red-violet, single to multiple ringlike

  structure

  • loop or figure-eight shapes

• Seen in megaloblastic anemia, myelodysplastic syndromes, lead poisoning

• fragments of nuclear material

Hemoglobin C crystals

• Condensed, intracellular, rod-shaped crystal

• Seen in hemoglobin C or SC disease, but not in trait

Hemoglobin SC crystals (Washington monument)

• One to two blunt, fingerlike projections extending from the cell membrane

• Seen in hemoglobin SC disease

Heinz bodies

• must use a supravital stain to visualize

• Seen in G6PD deficiency, beta-thalassemia major, Hgb H disease, unstable hemoglobinopathies, drug-induced anemias

• denatured hemoglobin

Malarial parasites

P. vivax, P. falciparum, P. malariae, and P. ovale

Erythrocyte Hemoglobin Content and Associated Diseases

• Normochromasia

• Hypochromasia

• Polychromasia

• Hyperchromasia/Spherocyte

Hypochromasia

• MCH and MCHC ↓

• Microcytosis

Polychromasia

• blue w/ wright stain

• reticulocytosis

• slightly macrocytuc

Rouleaux

• Stacking or “coining” pattern

• due to abnormal or inc. plasma proteins

• Seen in hyperproteinemia, multiple myeloma, Waldenström macroglobulinemia, and conditions that produce increased fibrinogen (chronic

  inflammation)

• normal in thicker area of the peripheral smear

Agglutination: cold autoimmune hemolytic anemia (cold agglutinin disease)

• No pattern in clumping

• RBCs coated w/ IgM and complement

• Warm blood to 37°C to correct a false low RBC and hematocrit, and false high

  MCHC (>37 g/dL)