Red blood cells

• What is the structure and function of red blood cells?


  • bioconcave disc
  • no nucleus
  • pliable, high surface area
  • unable to divide or make new proteins - bag of haemoglobin and enzymes for glycolysis
  • main function - O2 and CO2 transport, acid/base balance
  • able to maintain membrane integrity and prevent oxidation
• What is the distribution of haematopoesis by age?


  Yolk sac (0-2 months), Liver (1 month to birth)

  Post birth - bone marrow

  • from birth to around 20 - 25 your blood comes from your tibia and fibula
  • most of your blood comes from your vertebra, sternum and ribs - in order
• What are the stroma (cells) of the bone marrow?


  • Fibroblasts
  • macrophages
  • endothelium
  • fat cells
• What growth factors drive the maturation of RBC?


  • tend to mature towards the venous blood channels
  • Drives red blood cell creation
  • erythropoietin
  • interleukin 3
  • androgens - more in men
  • thyroxine - from thyroid, people with under active thyroid tend to be slightly anaemic
  • growth hormone
• Where do Red blood cells develop?


  Around macrophages (iron store) in marrow - RBC get transferred iron from the macrophages
• What are reticulocytes?


  • Red cell that has left the marrow in the last 24 hours, nucleus has been taken out but hasn't fully matured
  • can tell by the prensence of reticulin - remnants of ribosomal mRNA, will be removed by the spleen
  • Useful measure of marrow response to anaemia or treatment
• What is required to make blood?

  • iron
  • folic acid
  • B12
• Where does iron come from?

  Haem iron - from meat based products

  Non - haem iron - from leafy green veg, like beans, lentils etc.
• How is iron absorption regulated?

  • Hepcidin regulates the absorption and the release from macrophages
  • the release increases during inflammatory disease - less iron is available
  • We have no mechanism to excrete iron
• How is iron transported?

  • transferrin - transport/recycling - circulate in the blood
  • when passing cells that need iron, cell expresses transferrin receptors, transferrin attaches to the cell and is internalised where it releases the iron and then is let go
• what is ferritin?


  The insoluble form of storage iron - better measure of iron stores
• How can iron be lost?


  • through mestruation
  • minor trauma
  • blood sampling
  • very small amounts in urine/ skin shedding
• Where is folic acid absorbed?


  • in the upper small bowel
• Where is B12 absorbed?


  • in the terminal ilieum
• Where is B12 stored?


  • in the liver, taken there by transcobalamin via portal circulation
• Why are B12 and folate required in RBC production?


  • required to make thymidine to make DNA
• What is erythropoetin?


  • Hormone that is produced mostly in the kidney, some in the liver
  • there are no body stores of this hormone so production is switched on by;
  • tissue hypoxia or anaemia
  • high altitude
  • epo producing tumours eg renal
• How is erythropoietin regulated?


  Perinephric cells - cells in the kidney - sense a low oxygen level in the blood - more erythropoietin is produced - homeostasis
• What is the membrane of RBC made of?

  • lipid bi layer with protein 'skeleton' bound to it
  • Malleable - contain spectrin - tethered to the inside of the cell membrane - very springy
• What is the structure of Haemoglobin molecule?


  • 2 alpha - like chains - each chain will have one heam attached to it
  • 2 beta - like chains
  • Hb A (adult) - 2 alpha, 2 beta
  • Hb F (foetus) - 2 alpha, 2 gamma
• What is the oxygen dissociation curve?


  A graphical representation of oxygen being offloaded by blood cells

  • Key function is to bind haemoglobin to oxygen at high oxygen tension and release it at low oxygen tension
  • Oxygen gets delivered to the tissues that need it
• What could cause the oxygen dissociation curve to shift to the right?


  • acidosis
  • increased temperature - exercise, illness etc will cause more oxygen to be delivered to the tissues that need it
• How is oxygen released from the haemoglobin?


  2,3 DPG (diphosphoglycerate) enters the globin chains releasing oxygen

  • 2,3 DPG levels increase in exercise/anaemia/high altitude
• What is myoglobin?


  Myoglobin is a protein that is responsible for the storage and transport of oxygen - only in muscles

  • it is a 'last ditch' oxygen reserve in severe exertion - oxygen dissociation curve far to the left of haemoglobins
  • after this is used up - anaerobic respiration is used to continue to supply oxygen to the muscles
• What is the normal pH of the body?


  7.35 - 7.25
• Why is the acid base balance important?


  • enzymes work optimally at physiological pH - must be maintained or enzymes won't work as well, may become denatured
  • Cell membranes become leaky in acidoses - leak potassium
  • Neurones become less able to transmit in acidoses - hyperactive in alkalosis
• The body has to have natural buffer systems to try to maintain the optimal pH. Explain these buffer systems.


  Haemoglobin buffer

  • once haemoglobin has gotten rid of its oxygen, it can bind with hydrogen
  • a low pH decrease haemoglobins affinity for oxygen

  Bicarbonate buffer

  • Naturally occurring bicarbonate in the blood neutralises hydrogen through a reaction that produces water and carbon dioxide
• What occurs as RBC age?


  • membrane becomes more rigid - doesn't deform as well when going through blood vessels
  • Loss of glycolytic enzymes
  • New-antigens exposed on cell surface - due to surface being so worn away
• How is haemoglobin recycled?


  • Free haemoglobin is 'mopped up' by haptoglobin and delivered to liver
  • Globin chains can be broken up into their individual amino acids
  • Iron bound becomes bound to transferrin and is returned to macrophages
  • Porphyrin ring become bilirubin (yellowy pigment in blood) - head to liver