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Carbon Dioxide Transport

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Abstract

The sections in this article are:

1 Carbon Dioxide Content of Blood
1.1 Dissolved CO2
1.2 Bicarbonate Ion
1.3 Carbamate Compounds
2 Carbon Dioxide Dissociation Curve
2.1 Buffering of CO2
2.2 Distribution of CO2 Content Between Cells and Plasma
2.3 Haldane Effect
2.4 Relative Contributions to CO2 Exchange
3 Time‐Dependent Factors in CO2 Exchange
3.1 Diffusion of CO2
3.2 Dehydration of Carbonic Acid
3.3 Bicarbonate‐Chloride Exchange
3.4 Interaction of CO2 and O2 Exchange
3.5 Models of Gas Exchange
Figure 1. Figure 1.

Pathways for hydration‐dehydration reaction. The k2k2 reaction is much faster than other two reactions, which are rate limiting for the process.

Figure 2. Figure 2.

Arrhenius plot illustrating effect of temperature on constants involved in CO2 reactions. Straight lines fitted to experimental data are given by Constant (log10) = m [103/T(°K)] + b; m and b values for each process are listed in figure.

Data for feoir from Pinsent et al. and Sirs . Data for from Edsall . Data for from Roughton . Hydration constant Kh computed from and
Figure 3. Figure 3.

Effect of pH on Michaelis constant (Km; A) and turnover number (kcat; B) of human carbonic anhydrase I (HCA‐B) and II (HCA‐C) at 25°C and 0.2 M ionic strength. The pH variation of kcat/Km is result of changes in kcat because Km is constant over this pH range. The following buffers were used in the experiments: ▿, 3,5‐lutidine; ○, imidazole; □, N‐methylimidazole; Δ, 1,2‐dimethylimidazole.

From Khalifah
Figure 4. Figure 4.

Oscilloscopic tracing of change in pH after rapid mixing (STOP) of solution containing CO2 with 4 mM glycylglycine at 37°C. pHA, pH of glycylglycine solution prior to mixing. pHB, pH of mixture after mixing but prior to reaction. pHequil, carbamate equilibrium; subsequent pH change is due to continuing uncatalyzed hydration of CO2. pHc, extrapolation of pH to time of mixing; this pH would occur as result of carbamate formation alone.

From Gros et al.
Figure 5. Figure 5.

Carbamate dissociation curves of human plasma at 37°C.

From Gros et al.
Figure 6. Figure 6.

Carbon dioxide content of deoxygenated solutions of human Hb at constant partial pressure of CO2 (Pco2, 40 Torr). Upper curve obtained in absence of 2,3‐DPG; lower curve obtained after addition of 2 mol 2,3‐DPG/mol Hb tetramer.

From Bauer
Figure 7. Figure 7.

Influence of 2,3‐diphosphoglycerate (2,3‐DPG) on Haldane effect in erythrocytes. •, Data obtained with carbonic anhydrase inhibition, ▴, Data obtained without carbonic anhydrase inhibition. Relative contributions of (clear areas) and carbamate (shaded areas) to total Haldane effect are labeled.

Adapted from Klocke
Figure 8. Figure 8.

Carbon dioxide bound to β‐chain (A) and α‐chain (B) of Hb selectively carbamylated at NH2‐terminal amino groups. ○, □, Deoxygenated solutions. •, ▪, Solutions of Hb liganded with CO. ○, •, Solutions free of 2,3‐DPG. □, ▪, Data obtained in presence of 2 mol 2,3‐DPG/mol Hb tetramer.

From Perrella et al. . Reprinted by permission from Nature, copyright 1975, MacMillan Journals Limited
Figure 9. Figure 9.

Carbon dioxide dissociation curve of human blood plotted on linear (A) and logarithmic (B) axes.

Data from Christiansen et al.
Figure 10. Figure 10.

Reactions of CO2 in pulmonary capillary. CA, carbonic anhydrase, either free inside cell or bound to capillary endothelium. ‐ ‐>, Dehydration reaction proceeds much more slowly in plasma than erythrocyte. →, Processes that proceed rapidly. ‐‐‐>, Participation of H+ associated with Hb buffering.

Figure 11. Figure 11.

Variation in Haldane effect as function of extracellular pH at Pco2 of 42.5 Torr in erythrocyte suspensions. •, Data obtained with carbonic anhydrase inhibition. x, Data obtained without carbonic anhydrase inhibition. Contributions of oxylabile carbamate and to total Haldane effect are indicated.

From Klocke
Figure 12. Figure 12.

Carbon dioxide excretion ( ) in isolated, blood‐free perfused rabbit lungs as function of perfusion rate ( ). ▴, Observed CO2 excretion. Δ, Expected excretion of CO2 dissolved in buffer, calculated from simultaneous measurements of excretion of acetylene dissolved in buffer. Shaded areas, CO2 generated in pulmonary capillary from contained in perfusate. Small amount of CO2 generated in presence of acetazolamide (B) is result of uncatalyzed dehydration reaction. Larger amount formed under control conditions (A) is due to catalysis of dehydration by capillary endothelial carbonic anhydrase.

From Klocke
Figure 13. Figure 13.

Lineweaver‐Burk plot of reciprocals of reaction velocity (V) and substrate ( ) concentration in presence of different concentrations of acetazolamide (ACTZ). •, 12 mM in perfusate; ○, 25 mM in perfusate; ▴, 35 mM in perfusate. Data obtained in isolated perfused rat lungs in absence of blood carbonic anhydrase. Catalysis is result of activity of pulmonary vascular carbonic anhydrase.

From Bidani et al.
Figure 14. Figure 14.

Computed effect of erythrocyte permeability ( ) and plasma catalysis (A0) of dehydration reaction on pulmonary CO2 exchange in resting human.

From Crandall and Bidani
Figure 15. Figure 15.

Kinetics of Haldane effect. Deoxygenated erythrocyte suspension was rapidly saturated (‐ ‐ ‐ ‐ ‐, righthand scale) and resulting liberation of CO2 (‐ ‐ ‐ ‐ ‐, lefthand scale) monitored in continuous‐flow rapid‐reaction apparatus. Lower solid curve was obtained during carbonic anhydrase inhibition and represents carbamate formation. Upper solid curve was obtained without enzyme inhibition and represents sum of changes due to both oxylabile and carbamate.

From Klocke


Figure 1.

Pathways for hydration‐dehydration reaction. The k2k2 reaction is much faster than other two reactions, which are rate limiting for the process.



Figure 2.

Arrhenius plot illustrating effect of temperature on constants involved in CO2 reactions. Straight lines fitted to experimental data are given by Constant (log10) = m [103/T(°K)] + b; m and b values for each process are listed in figure.

Data for feoir from Pinsent et al. and Sirs . Data for from Edsall . Data for from Roughton . Hydration constant Kh computed from and


Figure 3.

Effect of pH on Michaelis constant (Km; A) and turnover number (kcat; B) of human carbonic anhydrase I (HCA‐B) and II (HCA‐C) at 25°C and 0.2 M ionic strength. The pH variation of kcat/Km is result of changes in kcat because Km is constant over this pH range. The following buffers were used in the experiments: ▿, 3,5‐lutidine; ○, imidazole; □, N‐methylimidazole; Δ, 1,2‐dimethylimidazole.

From Khalifah


Figure 4.

Oscilloscopic tracing of change in pH after rapid mixing (STOP) of solution containing CO2 with 4 mM glycylglycine at 37°C. pHA, pH of glycylglycine solution prior to mixing. pHB, pH of mixture after mixing but prior to reaction. pHequil, carbamate equilibrium; subsequent pH change is due to continuing uncatalyzed hydration of CO2. pHc, extrapolation of pH to time of mixing; this pH would occur as result of carbamate formation alone.

From Gros et al.


Figure 5.

Carbamate dissociation curves of human plasma at 37°C.

From Gros et al.


Figure 6.

Carbon dioxide content of deoxygenated solutions of human Hb at constant partial pressure of CO2 (Pco2, 40 Torr). Upper curve obtained in absence of 2,3‐DPG; lower curve obtained after addition of 2 mol 2,3‐DPG/mol Hb tetramer.

From Bauer


Figure 7.

Influence of 2,3‐diphosphoglycerate (2,3‐DPG) on Haldane effect in erythrocytes. •, Data obtained with carbonic anhydrase inhibition, ▴, Data obtained without carbonic anhydrase inhibition. Relative contributions of (clear areas) and carbamate (shaded areas) to total Haldane effect are labeled.

Adapted from Klocke


Figure 8.

Carbon dioxide bound to β‐chain (A) and α‐chain (B) of Hb selectively carbamylated at NH2‐terminal amino groups. ○, □, Deoxygenated solutions. •, ▪, Solutions of Hb liganded with CO. ○, •, Solutions free of 2,3‐DPG. □, ▪, Data obtained in presence of 2 mol 2,3‐DPG/mol Hb tetramer.

From Perrella et al. . Reprinted by permission from Nature, copyright 1975, MacMillan Journals Limited


Figure 9.

Carbon dioxide dissociation curve of human blood plotted on linear (A) and logarithmic (B) axes.

Data from Christiansen et al.


Figure 10.

Reactions of CO2 in pulmonary capillary. CA, carbonic anhydrase, either free inside cell or bound to capillary endothelium. ‐ ‐>, Dehydration reaction proceeds much more slowly in plasma than erythrocyte. →, Processes that proceed rapidly. ‐‐‐>, Participation of H+ associated with Hb buffering.



Figure 11.

Variation in Haldane effect as function of extracellular pH at Pco2 of 42.5 Torr in erythrocyte suspensions. •, Data obtained with carbonic anhydrase inhibition. x, Data obtained without carbonic anhydrase inhibition. Contributions of oxylabile carbamate and to total Haldane effect are indicated.

From Klocke


Figure 12.

Carbon dioxide excretion ( ) in isolated, blood‐free perfused rabbit lungs as function of perfusion rate ( ). ▴, Observed CO2 excretion. Δ, Expected excretion of CO2 dissolved in buffer, calculated from simultaneous measurements of excretion of acetylene dissolved in buffer. Shaded areas, CO2 generated in pulmonary capillary from contained in perfusate. Small amount of CO2 generated in presence of acetazolamide (B) is result of uncatalyzed dehydration reaction. Larger amount formed under control conditions (A) is due to catalysis of dehydration by capillary endothelial carbonic anhydrase.

From Klocke


Figure 13.

Lineweaver‐Burk plot of reciprocals of reaction velocity (V) and substrate ( ) concentration in presence of different concentrations of acetazolamide (ACTZ). •, 12 mM in perfusate; ○, 25 mM in perfusate; ▴, 35 mM in perfusate. Data obtained in isolated perfused rat lungs in absence of blood carbonic anhydrase. Catalysis is result of activity of pulmonary vascular carbonic anhydrase.

From Bidani et al.


Figure 14.

Computed effect of erythrocyte permeability ( ) and plasma catalysis (A0) of dehydration reaction on pulmonary CO2 exchange in resting human.

From Crandall and Bidani


Figure 15.

Kinetics of Haldane effect. Deoxygenated erythrocyte suspension was rapidly saturated (‐ ‐ ‐ ‐ ‐, righthand scale) and resulting liberation of CO2 (‐ ‐ ‐ ‐ ‐, lefthand scale) monitored in continuous‐flow rapid‐reaction apparatus. Lower solid curve was obtained during carbonic anhydrase inhibition and represents carbamate formation. Upper solid curve was obtained without enzyme inhibition and represents sum of changes due to both oxylabile and carbamate.

From Klocke
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Robert A. Klocke. Carbon Dioxide Transport. Compr Physiol 2011, Supplement 13: Handbook of Physiology, The Respiratory System, Gas Exchange: 173-197. First published in print 1987. doi: 10.1002/cphy.cp030410