RBC Production, Function, and Morphology

which stem cell do RBC’s derive from?

CFU-GEMM

how long does it take for RBC’s to develop in the bone marrow?

5 days

what is the size of a pronormoblast?

18-20 μm

what is the N:C ratio of a pronormoblast?

6:1

what is the size of a basophilic normoblast?

16 μm

what is the N:C ratio of a basophilic normoblast?

6:1

what is the cytoplasm color of a pronormoblast?

dark blue/purple

what is the cytoplasm color of a basophilic normoblast?

cornflower blue

what is the size of a polychromatophilic normoblast?

13 μm

what is the N:C ratio of a polychromatophilic normoblast?

4:1

what is the cytoplasm color of a polychromatophilic normoblast?

blue layered with tinges of orange-red

in which stage of RBC development does hemoglobin begin to be synthesized?

polychromatophilic normoblast

what is the size of an orthochromic normoblast?

8 μm

what is the N:C ratio of an orthochromic normoblast?

1:1

what is the cytoplasm color of an orthochromic normoblast?

orange-red color tinges with slight blue tone

in which RBC developmental stage is the nucleus most small and dense?

orthochromic normoblast

what is the size of a reticulocyte?

8 μm

which RBC developmental stage includes remnants of RNA?

reticulocyte

how do reticulocytes appear in new methylene blue stain?

filamentous structure in chains or as a single-dotted structure

how do reticulocytes appear in wright’s stain?

large bluish RBC’s

what is the other name for reticulocytes?

polychromatic macrocyte

what is the size of a mature RBC?

6-8 μm

how large is the central pallor of a mature RBC?

1/3 the cell size (1-3 μm)

what is the order of RBC developmental stages?

• pronormoblast

• basophilic normoblast

• polychromatophilic normoblast

• orthochromic normoblast

• reticulocyte

• mature RBC

what form the outermost layer of a RBC, directly beneath the membrane surface?

glycolipids and glycoproteins

what forms the central layer of a RBC?

cholesterol and phospholipids

what forms the inner layer, or cytoskeleton, of a RBC?

spectrin, ankyrin, actin, and protein 4.1

what is the composition of the RBC membrane?

• 50% protein

• 40% lipid

• 10% cholesterol

what purpose does the lipid fraction of the RBC membrane serve?

barrier to most water-soluble molecules

what parts of the RBC include integral proteins?

cytoskeleton through membrane all the way to other edge of RBC surface

what parts of the RBC include peripheral proteins?

RBC cytoskeleton

what is the purpose of integral proteins?

provide backbone for active and passive transport, provide supporting structure for over 30 RBC antigens

what substances can freely cross RBC membrane?

water, chloride, and bicarbonate

what is the intracellular-to-extracellular ratio of sodium?

1:12

what is the intracellular-to-extracellular ratio of potassium?

25:1

which integral proteins give the RBC a net negative charge?

glycophorins A, B, and C

which part of the RBC plays an important role in the deformability and elasticity of the cell membrane?

cytoskeleton

which peripheral proteins are responsible for deformability properties of the RBC?

spectrin and ankyrin

what causes RBC to become spherocytes?

membrane becomes more permeable to sodium

what causes the production of spherocytes?

abnormalities of spectrin

what is the purpose of the embden-meyerhof pathway?

• provides 90% of ATP

• provides NAD+ from NADH, an important structure in the formation of 2,3-diphosphoglycerate, a key element for oxygen loading and unloading

what is the purpose of the phosphogluconate pathway?

• provides 5%-10% of ATP

• production of NADPH so that globin chains are not degraded by oxidative stress and accumulation of hydrogen peroxide

heinz body inclusions lead to what cell as they are pitted from the cell by the spleen?

bite cells

what is the purpose of the methemoglobin reductase pathway?

• maintains iron in ferrous state so hemoglobin can bind to oxygen

the methemoglobin reductase pathway is dependent on which chemical reaction?

reduction of NAD+ to NADH

what happens when NADH enzyme is deficient in the methemoglobin reductase pathway?

methemoglobin accumulates in the RBC, which is a form of hemoglobin which cannot bind with oxygen due to its reduced iron state

which four main clinical conditions lead to microcytic cells?

• iron deficiency anemia

• thalassemia

• sideroblastic anemia

• anemia of chronic disorders

why are iron-deficient RBC’s smaller than normal RBC’s?

they divide more rapidly searching for iron

how is iron incorporated into hemoglobin?

absorbed from the bloodstream and transferred, via transferrin, to the pronormoblasts of the bone marrow for incorporation into the four heme structures of each hemoglobin molecule

why does thalassemia lead to microcytic cells?

decreased or absent globin synthesis

why does anemia caused by inflammation lead to microcytes?

iron delivery to the reticuloendothelial system is impaired

which stage of developing RBC’s can be released prematurely by the bone marrow when the body is responding to anemic stress?

reticulocytes and sometimes orthochromic normoblasts

what characterizes the appearance of spherocytes?

dense, dark, and small compared to normal RBC’s

which kind of hemoglobin is found in sickle cells?

Hgb S

what characterizes the appearance of stomatocytes?

elongated central pallor approximately ¾ the diameter of the RBC

what characterizes the appearance of ovalocytes?

egg-shaped

elliptocytes derive from what?

abnormal spectrin and protein 4.1

what characterizes the appearance of target cells?

bull’s eye-shaped cell

which morphologies can form artifactually during slide preparation?

stomatocytes and target cells

what characterizes the appearance of acanthocytes?

smaller cell surrounded by uneven, thornlike spicules

what characterizes the appearance of burr cells?

smaller cell with projections arising from the cell surface

what are fragmented cells?

red blood cell fragments, such as schisocytes, true red blood cell fragments, helmet cells, and burr cells

what conditions can cause the formation of acanthocytes?

• abetalipoproteinemia

• neonatal hepatitis

• postsplenectomy

• vitamin E deficiency

• cirrhosis of liver with associated hemolytic anemia

• mcLeod syndrome

what conditions can cause the formation of burr cells?

• burns

• gastric carcinoma

• peptic ulcers

• renal insufficiency

• uremia

• pyruvate kinase deficiency

what conditions can cause the formation of ovalocytes/elliptocytes?

• hereditary ovalocytosis

• iron deficiency anemia

• megaloblastic anemia

• pernicious anemia

what conditions can cause the formation of schistocytes?

• burns

• heart valve implants

• disseminated intravascular coagulation (DIC)

• hemolytic uremia syndrome (HUS)

• thrombotic thrombocytopenic purpura (TTP)

• bite cells (G6PD deficiency)

• renal transplant

what conditions can cause the formation of spherocytes?

• ABO incompatibility

• disseminated intravascular coagulation (DIC)

• bacterial toxins

• autoimmune hemolytic anemias

• blood transfusion reactions

• hereditary spherocytosis

what conditions can cause the formation of stomatocytes?

• alcoholism

• hereditary spherocytosis

• malignancies

• Rh null syndrome

what conditions can cause the formation of target cells?

• hemoglobinopathies

• sickle cell thalassemia

• hemolytic anemias

• iron deficiency

• liver disease including cirrhosis

• postsplenectomy

what conditions can cause the formation of teardrops?

• myeloproliferative syndromes

• severe anemias

what are howell-jolly bodies?

remnants of DNA that appear as 1-2 μm round, deep structures in the cytoplasm

what are siderotic granules/pappenheimer bodies?

small, light purple, beaded iron inclusions along the periphery of RBC’s

what is the name of siderotic granules/pappenheimer bodies when using prussian blue vs. wright stains?

prussian blue: siderotic granules

wright’s stain: pappenheimer bodies

what is basophilic stippling?

RNA and mitochondrial remnants appearing as either dustlike or coarse granules in the cytoplasm

what are heinz bodies?

denatured hemoglobin which lead to bite cells when removed by the spleen