Carbon Dioxide Gas Transport Charles L. Webber, Jr., Ph.D.

Learning Objectives: You should be able to:

• List the three forms of carbon dioxide carried by the blood and how they interact to form the total CO2 dissociation curve.
• Diagram using pertinent chemical reactions how CO2 is processed by red blood cells traversing tissue and lung capillaries.
• Specify how hemoglobin functions as a hydrogen ion buffer in venous blood, contrasting principles of reduction versus titration.
• Contrast the changes in blood gas contents and partial pressures of oxygen and carbon dioxide during hyperventilation and hypoventilation.

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1. Three Forms of Carbon Dioxide in the Blood
   • physically dissolved CO2 (10%)
     • dissolved CO2 increases linearly with increases in PCO2 (obeys Henry's law)
     • CO2 solubility = 0.06 mL CO2/dLblood per mm Hg (20 times higher than O2 solubility)
     • dissolved CO2 fraction cannot be neglected
   • carbamino compounds (22%)
     • CO2 joins reversibly with non-ionized terminal amino groups (-NH2) of blood borne proteins
     • primary sites are 4 terminal amino groups of hemoglobin which are not ionized at pH = 7.40
     • 44 other terminal amino groups of hemoglobin are ionized and unusable (-NH3+)
   • bicarbonate ion formation (68%)
     • most CO2 in the blood is transported in the bicarbonate ion form
     • bicarbonate ion is formed from the CO2 hydration reaction accelerated by carbonic anhydrase: CO2 + H2O H2CO3 H+ + HCO3-
     • red blood cells are crucial for production of HCO3- from CO2 because of the presence of carbonic anhydrase

    

2. Total CO2 Dissociation Curve

   

   • total CO2 content depends on the summation of the three CO2 components
   • total CO2 content in blood is a hyperbolic function of PCO2

      

    

3. Shifts in the CO2 Dissociation Curve

   

   • oxygen shifts the carbon dioxide dissociation curve to the right (Haldane effect)
     • presence of O2 decreases the affinity of hemoglobin for CO2
     • at PaO2 = 95 mm Hg, CO2 curve is shifted down and to the right (lower curve)
     • at PvO2 = 40 mm Hg, CO2 curve is shifted up and to the left (upper curve)
   • total CO2 content in the blood must be read from proper curve
     • at PaCO2 = 40 mm Hg; CaCO2 = 50 mL CO2/dLarterial blood (point a)
     • at PvCO2 = 46 mm Hg; CvCO2 = 54 mL CO2/dLvenous blood (point v)
   • concurrent changes in PO2 and PCO2 form a physiological dissociation curve (dashed line)
     • in the tissues, CO2 content moves up from point a to point v
       low PO2 in the tissues facilitates CO2 loading (reverse Haldane effect)
       high PCO2 in the tissues facilitates O2 unloading (Bohr effect)
     • in the lungs, CO2 content moves down from point v to point a
       high PO2 in the lungs facilitates CO2 unloading (Haldane effect)
       low PCO2 in the lungs facilitates O2 loading (reverse Bohr effect)

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C02 Processing by Red Blood Cells

1. Carbon Dioxide Reactions in the Blood

   

   • plasma reactions
     • 10% CO2 processing
     • lack of carbonic anhydrase
   • red blood cells
     • 90% CO2 processing
     • presence of carbonic anhydrase

        

    

2. Gradients Established Across the Red Blood Cell Membrane
   • diffusion gradient
     • CO2 is produced by tissue metabolism
     • CO2 moves down its partial pressure gradient from tissue space to capillary blood
   • concentration gradient
     • rapid hydration of CO2 produces a high concentration of HCO3- within RBCs
     • HCO3- diffuses out of RBCs down its concentration gradient
   • electrical gradient
     • HCO3- movement builds up a net positive charge within RBCs
     • H+ cannot move across membrane (cation barrier)
     • Cl- from the plasma moves into RBCs down its electrical charge gradient
     • a Donnan equilibrium is established between HCO3- and Cl- across RBC membrane
   • pH gradient
     • not entirely buffered, H+ ions accumulate within RBCs
     • increase in intracellular [H+] leads to a fall in pH below that of plasma
   • osmotic gradient
     • summed reactions leads to increased RBC osmolarity
     • water moves into RBCs down its osmotic gradient
     • RBCs swell on the venous side of the circulation
   • diffusion gradient
     • partial intracellular buffering of H+ drives O2 from hemoglobin (Bohr effect)
     • O2 moves down its partial pressure gradient from capillary blood to tissue space

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Hemoglobin as a Hydrogen Ion Buffer

• pH Gradient Across RBC Membrane and Respiratory Quotient
  • respiratory quotient (RQ) = mmol CO2 produced/mmol O2 consumed (in tissues)
  • respiratory gas exchange ratio (R) = mmol CO2 exhaled/mmol O2 inhaled (in lungs)
  • RQ = R in steady state (ventilation matched to metabolic demands)

  Fuel	RQ	mmol H+	pH RBC	Ph ven	pH art
  fats	0.7	0.7	7.40	7.40	7.40
  proteins	0.8	0.8	7.25	7.37	7.40
  carbohydrates	1.0	1.0	7.10	7.34	7.40

   

  Titration Curves of Oxygenated and Deoxygenated Blood (Fig. 30)

  • HHB in venous blood is a weaker acid (higher affinity for H+)
  • HHBO2 in arterial blood is a stronger acid (lower affinity for H+)
  • hemoglobin reduction pathway (point A to B)
    • for RQ = 0.7, H+ produced perfectly buffered without fall in pH
  • hemoglobin titration pathway (point B to C)
    • for RQ > 0.7, H+ produced partially buffered with fall in pH
  • slope of tritation curve depends directly upon hemoglobin concentration

   

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Blood Gas Contents and Ventilation

• Superimposition of Dissociation Curves

  

  • points N and N': normal operating points during eupnea
  • points I and I': shifted points during increased ventilation (hyperventilation)
  • points D and D': shifted points during decreased ventilation (hypoventilation)

   

• Hyperventilation and Hypoventilation Maneuvers (Fig. 31)
  • changes in _A cause large changes in PaO₂ and PaCO2
  • large changes in PaO2 result in small changes in CaO₂ (flatness of O₂ curve)
  • large changes in PaCO₂ result in large changes in CaCO₂ (steepness of CO₂ curve)

     

   

• Significance
  • it is possible to effect changes in blood CO₂ levels without jeopardizing oxygen content of the blood
  • this is important for acid base regulation in health and disease

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