Q1i / 14A11: Formation, structure, function & fate of RBC

14A11: Exam Report

Outline the formation, structure and function of the adult red blood cell.

19% of candidates passed this question.

Candidates  generally  provided  detailed  description  of  the  cell  lineage  that  led  up  to  the production  of  the mature  red  blood  cell  (RBC),  but  often  omitted  to mention  those aspects unique  to the RBC that were essential  to its  functions  (e.g. biconcave shape gives  the RBC a greater  surface  area  and  shorter  distance  to  central  regions,  thus  optimising  diffusion  of gases; the RBC enhanced ability to change shape and travel through narrow capillaries; lack of organelles  maximises  space  for  Hb,  etc.). Mention  of  RBC  function  often  lacked  detail  (e.g. restricted to just mentioning “O2 carriage”) or failed to mention, and describe, the RBC’s role in acid base buffering and HCO3B production.

Q1i / 14A11: Formation, structure, function & fate of RBC

  • Definition – the commonest cell in the blood
  • 4-6 million RBC/microlitre

Formation

  • KA Erythropoiesis
  • Occurs in Bone Marrow
  • Lineage:

PLUEIRPOTENT HAEMATOPOIETIC STEM CELL

↓

COLONY FORMING UNIT (CFU)

i.e. Myeloid Stem Cell

↓

COLONY FORMING UNIT ERYTHROCYTE (CFU-E)

↓

PROERYTHROBLAST (Nil Hb, nucleus)

↓

BASOPHIL ERYTHROBLAST (little Hb)

↓

POLYCHROMATOPHILIC ERYTHROBLAST (↑ Hb, ↓ nucleus size)

↓

NORMOBLAST (small dense nucleus which is ejected)

↓

RETICULOCYTE (RNA to make Hb, few mitoch., 1% of circulating RBC)

↓ diapededis (squeezes through cap pores) circulates ~2nd & loses RNA

 = MATURE RBC

  • As RBC develops, ↓size, ↑Hb, Nucleus disappears
  • From stem cell →  RBC ~10 days
  • Requires folate, B12, Fe

Regulation

  • Stimulated by EPO
  • EPO = glycoprotein synthesised in peritubular caps of kidney (90%) & liver (10%)
  • EPO circles blood stream
  • Acts on EPO receptor in BM
  • Differentiation & proliferation of cells into RBC
  • ↓O2 delivery due to
    • Anaemia
    • Hmmrg
    • ↑altitude
    • Lung disease
    • HF

Rbc Structure

  • Round, biconcave disc
    • Large SA for gas transfer
  • Diam 7µm, width 2µm
    • Notoriously deformation →  allows movement through tiny caps
  • Smooth contours
  • Lipid bilayer, negative surface charge
  • Enzymes:
    • NA/K/ATPase – allows structure/maintenance
    • Carbonic Anhydrase – allows CO2 + H2O ⮂ H2CO3 ⮂ H+ + HCO3–
    • Anucleus, nil mitochondria
      • Less E. requirements
      • More room for Hb
      • E via anaerobic glycolysis & pentose phosphate pathway

Hb

  • Protein
  • 200 – 300 million molecules Hb in each RBC
  • 2 parts: heme + globin
  • Heme moiety has PROTOPORPHYRIN RING & central iron in Ferrous (Fe2+) state
  • 4 polypeptide chains determine type of Hb
  • O2 binds reversibly to heme
  • 4 hemes →  ∴carries 4 x O2
  • Hb is allosteric →  binding O2 to 1 heme = ↑affinity for remaining O2

Function

1. To Carry Hb

  • Allows Hb to remain a tetramer
  • Protects protein from glomerular filtration
  • Avoids ∆ plasma oncotic P

2. O2 Transport

  • 1° function
  • O2 binds Hb →  transported to tissues
  • BOHR EFFECT enhances this →  ↑PCO2 / ↑H+ causes ↓affinity for O2 & offloads to tissues (because Hb is simply growing BOHR-ed of O2)

3. CO2 Transport

  1. Carbamino compounds →  terminal groups of Hb
  2. HCO3– →  catalysed by CA

4. Acid/Base Buffer

  • H+ binds HbO2
  • Conformational ∆ →  release O2

5. Cl – Shift

  1. Carbamino compounds →  terminal groups of Hb
  2. HCO3– →  catalysed by CA

6. Immunological Role

  • ABO Ags

RBC Fate

  • RBC lifespan ~120 days
  • Ageing RBC undergoes PM ∆ →  recognised by macrophages →   remove old & defective RBCs
  • ­KA ERYPTOSIS
RBC fate