rbc production and destruction

• Erythrocyte


  Red blood cell
• Erythrocyte


  • Its one true function is 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
  • Its role in returning carbon dioxide to the lungs and buffering the pH of the blood is important but quite secondary to its oxygen-carrying function
• The mammalian erythrocyte is unique among animal cells in that in its mature, functional state, it does not have a nucleus
• Normoblastic maturation


  The process of erythroid precursors developing from immature to mature cell stages
• Erythroid precursor nomenclatures


  • Normoblastic
  • Rubriblastic
  • Erythroblastic
• Normoblastic proliferation


  1. Replication (division) to increase cell numbers

  2. Development from immature to mature cell stages
• Criteria for identifying erythroid precursors

  • Nuclear chromatin pattern (texture, density, homogeneity)
  • Nuclear diameter
  • Nucleus-to-cytoplasm (N:C) ratio
  • Presence or absence of nucleoli
  • Cytoplasmic color
• Trends affecting erythroid precursor appearance

  • Overall cell diameter decreases
  • Nuclear diameter decreases more rapidly than cell diameter, so N:C ratio decreases
  • Nuclear chromatin becomes coarser, clumped, and condensed
  • Nucleoli disappear
  • Cytoplasm changes from blue to gray-blue to salmon pink
• Erythroid maturation sequence


  1. Pronormoblast

  2. Basophilic normoblast

  3. Polychromatic normoblast

  4. Orthochromic normoblast

  5. Bone marrow polychromatic erythrocyte (reticulocyte)

  6. Erythrocyte
• Pronormoblast


  • The earliest morphologically recognizable erythrocyte precursor, derived from pluripotent hematopoietic stem cells
  • Has a round to oval nucleus with 1-2 nucleoli and dark blue cytoplasm due to concentration of ribosomes and RNA
  • Undergoes mitosis to give rise to 2 daughter pronormoblasts, with potential for more than 1 division before maturing into basophilic normoblasts
• ast


  1. 10 μm
• 1. 2


  Nucleus to cytoplasm ratio
• 5%-10%


  Percentage of cells
• 48 hr


  Duration of stage
• Bone marrow polychromatic erythrocyte


  Also called reticulocyte
• 1. 10 μη


  Cell diameter
• No nucleus
• 1%


  Percentage of cells
• 24-48 hr


  Duration of stage
• Polychromatic erythrocytes


  Erythrocytes that appear bluish in colour due to the presence of residual ribosomes, indicating they are newly released from the bone marrow
• Polychromatic erythrocytes


  • Figure 5.8A
  • Figure 5.8B
• Reticulocytes


  Polychromatic erythrocytes that have been stained to reveal the mesh of small blue strands (reticulum) of residual ribosomes
• Polychromatic erythrocytes are also called diffusely basophilic erythrocytes due to their bluish tinge
• Basophilic stippling


  Distinct dots of blue throughout the cytoplasm of red blood cells, associated with some anemias
• Basophilic stippling is due to degenerate residual ribosomal RNA
• Erythrocyte


  Mature red blood cell that is a biconcave disc measuring 7-8 μm in diameter and 1.5-2.5 μm in thickness
• Mature erythrocytes lack a nucleus
• Mature erythrocytes appear salmon-pink with a central pale area on a Wright-stained blood film
• Erythrocytes cannot divide
• Mature erythrocytes remain active in circulation for approximately 120 days
• Erythrocytes


  • Deliver oxygen to tissues, release it, and return to the lung to be reoxygenated
  • Have a high surface area-to-volume ratio and biconcave shape to enable optimal gas exchange
  • Have a flexible, deformable membrane to squeeze through small spaces
• Erythrokinetics


  The dynamics of red blood cell production and destruction
• Erythron


  The collection of all stages of erythrocytes throughout the body, including developing precursors in the bone marrow and circulating erythrocytes
• Hypoxia


  Inadequate tissue oxygen
• Oxygen sensing system


  • Located in peritubular fibroblasts of the kidney
  • Detects hypoxia and produces erythropoietin to stimulate red blood cell production
• Hypoxia-inducible factors (HIFs)


  Transcription factor proteins that respond to hypoxia by increasing erythropoietin gene transcription
• Erythropoietin (EPO)


  Glycoprotein hormone produced by the kidney that stimulates red blood cell production
• Actions of erythropoietin


  • Initiates intracellular signaling in erythroid progenitor cells
  • Increases cell division and maturation
  • Increases intestinal iron absorption and hemoglobin synthesis
  • Allows early release of reticulocytes from bone marrow
  • Prevents apoptotic cell death
  • Reduces time for cells to mature in bone marrow
• EPO receptor


  Transmembrane protein homodimer that binds erythropoietin and activates downstream signaling pathways
• EPO induces changes in the adventitial cell layer of the bone marrow/sinus barrier


  Increases the width of the spaces for RBC egress into the sinus