--HEMATOPOIESIS-- PART TWO

• The erythrocyte has one true function: to carry oxygen from the lung to the tissues,

  where the oxygen is released.
• This is accomplished by the attachment of the oxygen to hemoglobin, the major cytoplasmic component of mature RBCs.
• The role of the RBC in

  returning carbon dioxide to the lungs and buffering the pH of the blood is important but is quite

  secondary to its oxygen-carrying function.
• RBCs are formally called

  erythrocytes
• Nucleated RBC precursors, normally restricted to the bone marrow, are called

  erythroblasts
• RBCs are formally called erythrocytes. Nucleated RBC precursors, normally restricted to the bone marrow, are called erythroblasts. They also may be _

  normoblasts
• developing nucleated RBC precursors (blasts) with normal appearance

  normoblasts
• The earliest identifiable progenitor committed to the erythroid lineage

  Burst-Forming Unit–Erythroid
• defined in vitro by its ability to create a “burst” on semisolid medium

  BFU-E
• The generation of BFU-E from hematopoietic stem cells requires

  (IL)-3

  stem cell factor

  erythropoietin
• The generation of BFU-E from hematopoietic stem cells requires interleukin (IL)-3, stem cell factor, and erythropoietin for

  differentiation

  proliferation

  prevention of apoptosis

  maturation
• BFU-E is a colony consisting of several hundred to thousands of cells by 10 to 14 days of growth, during which time smaller satellite clusters of cells form around a larger central group of erythroid cells, giving rise to the designation of a “burst.”
• As erythroid maturation progresses, a later progenitor, the _ derived from the BFU-E, can be defined _

  CFU-E

  in vitro
• CFU-E is dependent on _ for its

  development and can undergo only a few cell divisions.

  erythropoietin
• the CFU-E forms a smaller colony of morphologically recognizable _ in _ to _ days.

  erythroid cells

  5

  7
• Adhesion between _ and _ occurs at the CFU-E stage of maturation.

  erythroid cells

  macrophages
• Using cell-surface markers, IL-3 receptor, CD34, and CD36, highly purified populations of BFU-E and CFU-E can be isolated from human marrow.
• _ show distinctive changes in gene expression profiles in hematopoietic stem cells, BFU-E, and CFU-E

  Gene expression profiling
• Some of the marrow failure syndromes are the result of defects in differentiation

  of stem cells into erythroid progenitors.
• Pronormoblast (Rubriblast)

  takes up much of the cell

  nucleus
• The nucleus takes up much of the cell (N:C ratio

  8:1
• chromatin is open and contains few,

  if any, fine clumps. Pronormoblast (Rubriblast)

  purple red
• is round to oval, containing one or two nucleoli.

  nucleus
• The cytoplasm is dark blue because of the concentration of ribosomes and RNA.

  The Golgi complex may be visible next to the nucleus as a pale, unstained area.

  Pronormoblasts may show small tufts of irregular cytoplasm along the periphery of the membrane.
• pronormoblast undergoes _ and gives rise to two daughter

  pronormoblasts. More than one division is possible before maturation into basophilic

  normoblasts.

  mitosis
• The pronormoblast is present only in the _ in healthy states

  bone marrow
• begins to accumulate the components necessary for hemoglobin production


  pronormoblast
• The proteins and enzymes necessary for iron uptake and protoporphyrin synthesis are produced.

  pronormoblast
• Globin production begins

  pronormoblast
• This stage lasts slightly more than 24

  hours.


  pronormoblast
• The chromatin begins to condense, revealing clumps along the periphery of the

  nuclear membrane and a few in the interior.

  Basophilic Normoblast (Prorubricyte)
• Basophilic Normoblast (Prorubricyte) As the chromatin condenses, the _areas become larger and sharper


  parachromatin
• the N:C ratio decreases to about

  6:1


  Basophilic Normoblast (Prorubricyte)
• The chromatin stains deep purple-red. Nucleoli may be present early in the stage but disappear later.

  Basophilic Normoblast (Prorubricyte)
• When stained, the _may be a deeper, richer blue than in the pronormoblast, hence the name basophilic for this stage. 


  cytoplasm
• The chromatin pattern varies during this stage of development, showing some

  openness early in the stage but becoming condensed by the end.

  Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
• The condensation of chromatin reduces the diameter of the nucleus considerably, so the N:C ratio decreases from 4:1 to about 1:1 by the end of the stage. Notably, no nucleoli are present.

  Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
• This is the first stage in which the pink color associated with stained hemoglobin

  can be seen.

  Polychromatic (Polychromatophilic) Normoblast (Rubricyte)
• The stage’s name refers to this

  combination of multiple colors, because _ means “many color loving.”

  polychromatophilic
• The stained color reflects the accumulation of hemoglobin pigmentation over time and concurrent decreasing amounts of RNA.

  Polychromatic (Polychromatophilic) Normoblast (Rubricyte)