T3 L1: Function and formation of RBCs and Hb

• Why is Hb needed to carry O2?

  because O2 is poorly soluble in plasma

  hence it is possible for arterial PO2 to be normal but hypoxia to occur (as there is no Hb to carry O2)

  
• What is Haemoglobin?

  95% of dry weight of RBC

  each subunit has small haem group + large globin peptide

  Haem: coloured, contains one iron atom, site of O2 binding

  allosteric properties: cooperativity (binding at one point of molecule changes its structure at another point)

  
• What is the Haem group?

  carries O2

  porphyrin ring

  rigid, 2D, highly coloured due to sharing of electrons

  conjugated to Ferrous Fe2+ ion

  O2 molecule binds to Fe2+ without oxidising it

  
• What is myoglobin?

  oxygen-storage compound in muscle cells

  has only one globin subunit so does not have cooperativity
• What is 'cooperativity' of Haemoglobin?

  each subunit can carry one O2 molecule in its haem

  O2 binds to haem → radical conformational change of globin subunit → influence its 3 neighbours:

  • Above 50% sat: O2 binding causes more O2 binding
  • Below 50% sat: O2 release causes more O2 release
• What is HbA?

  adult haemoglobin

  2 alpha + 2 beta subunits (tetramer)

  'maternal haemoglobin)
• What is HbF?

  foetal haemoglobin

  2 alpha + 2 gamma subunits

  adults have small percentage of HbF (some pathologies may have higher)

  binds O2 more strongly than HbA
• What is the 'Bohr effect'?

  increased blood CO2 level causes decreased affinity of Hb for O2

  decreased pH too
• How is CO2 transported in blood?

  10% as dissolved

  22% as carbamino Hb

  68% as HCO3-

  
• What is 'chloride shift'?

  more Cl- inside RBCs in venous blood than arterial

  as Cl- taken into RBC to get HCO3- out

  
• What does the Hb saturation curve show?

  1. exercising tissue
  2. Resting tissue
  3. lungs

  
• Why is the Hb saturation curve sigmoidal in shape?

  above 93% saturation is not sensitive of PaO2

  
• What does left shifting of the Hb saturation curve mean?

  more O2 stays on Hb, less delivered

  
• What is the difference between PaO2 and SpO2?

  PaO2 = partial pressure of O2 dissolved in arterial plasma

  SpO2 = the nominal saturation of Hb in peripheral tissue as measured by a pulse oximeter on the finger.
• What would be a case of a patient's both oxygen readings (SpO2 and PaO2) to be normal, yet O2 delivery to be low?

  anaemia

  Hb dysfunction
• What does a right shift mean in the Hb saturation curve?

  decreased affinity for O2

  less O2 stays on Hb, more O2 delivered

  
• What factors cause a right shift in the haemoglobin dissociation curve when increased levels in blood?

  CO2

  H+

  Cl-

  2,3-DPG
• What is 2,3-DPG?

  binds to Hb and lowers affinity for O2

  
• What type of Hb has a lower affinity for 2,3-DPG?

  HbF

  less likely to be bound to 2,3-DPG which decreases affinity

  hence HbF higher affinity for oxygen

  
• What is the difference between O2 saturation curves of HbA and myoglobin?


  HbA: S shaped (due to cooperativity)

  Myoglobin: exponential

  
• What are the characteristics of blood in active muscle?


  low O2, high CO2, acidic, high temperature, myoglobin

  causes:

  • O2 leaves Hb
  • CO2 and H+ bind to Hb (shift saturation to right)
  • HCO3- leaves RBC → plasma
  • Cl- leaves plasma → enters RBC (Cl- shift)
• What is the main drive to increase respiratory rate?

  H+ in cerebrospinal fluid
• What are eryhtrocytes?


  red blood cells
• What is 'Packed cell volume' (PCV)?

  proportion of blood that is made up of cells
• What is 'Mean Cell Haemoglobin' (MCH)?


  Amount of hemoglobin in a red blood cell.
• What is 'Mean Corpuscular Volume' (MCV)?

  Red blood cell size.
• What is the site of erythropoiesis after birth?


  bone marrow only

  after age 20: primarily central bones (eg vertebrae)
• What is the site of erythropoiesis during embryogenesis?


  • liver
  • spleen
  • lymph nodes
  • yolk sac
• What is Haematopoiesis?


  development of blood cells
• Erythrocytes are of myeloid origin.
• How is the development of eryhtrocytes from stem cells?


  multipotent stem cells → multipotent progenitor cells → lineage-committed progenitor cells → mature cells (terminal differentiation)
• What are erythroblasts?


  lineage committed progenitor cells, but still very different than RBCs
• What are the 4 stages of the RBC?

  hematopoietic stem cell → erythroblast → reticulocyte → erythrocyte (RBC)

  
• What is Eryhtropoietin (EPO)?


  A cytokine / hormone that drives erythropoiesis

  can be used as a performance enhancing drug for athletes

  Or to treat anaemia
• What are reticulocytes?


  immature RBC precursor

  lasts 2 days in blood (then become RBC)

  reticulocyte count is a diagnostic tool for anaemia
• What can reticulocyte count be used to diagnose?


  anaemia

  indicator of bone marrow activity

  high reticulocyte count in haemolytic anaemias (homeostatic - destruction of RBCs)

  machine counts cells and detects those with basophilic material (eg DNA)
• What is Methaemoglobinaemia?


  Hb cannot transport O2

  Fe in Hb oxidised to Fe3+

  Symptoms: dyspnoea, pallor/cyanosis

  Diagnosis: eg PaO2 appears normal but O2 delivery low

  Due to:

  • congenital globin mutations
  • hereditary decrease of NADH
  • various toxic substances, poisons, drugs
• What is Carbon monoxide poisoning?


  CO displaces O2 from Hb

  affinity for CO is 250x stronger

  Hb cannot transport O2

  PO2 dissolved in blood remains normal

  Symptoms: blood turns bright red

  Brain affected first: disorientation

  Treatment: 100% O2 (replaces CO by mass action)
• What are Polycythaemias?


  increased number of RBCs (high PCV) → increased blood viscosity → clog blood vessels

  Two types:

  1. Physiologic polycythaemia: due to living at high altitude
  2. Polycythaemia vera: neoplasm
• What is Polycythaemia vera?


  neoplasm

  increased PCV → increased blood viscosity → clog blood vessels

  risk of thrombotic events

  no cure, treat with venesection (removal of excess blood by blood letting)

  often asymptomatic