16.2: CO₂ Transport
- Page ID
- 34653
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Unlike oxygen, carbon dioxide is soluble enough that it does not need a protein carrier like oxygen needs hemoglobin to enter and exit plasma. However, this does not necessarily mean that CO2 transport is simple. The complication this time is that free dissolved CO2 forms carbonic acid, which can threaten pH homeostasis. So most CO2 is not transported in the dissolved form. Most (approximately 70 percent) of the CO2 that emerges from metabolizing tissue is converted to bicarbonate with the help of enzymes within red blood cells. We will look at this more closely in a moment. About 15–25 percent is transported on hemoglobin.
Transport on Hemoglobin (15–25 Percent)
Carbon dioxide can bind to the terminal amine groups of hemoglobin’s polypeptide chains forming carbaminohemoglobin. It is worth noting a couple of points about this. First, CO2 does not compete with oxygen to bind to Hb—the binding sites are completely different and hemoglobin can hold both CO2 and O2 at the same time. Second, deoxyhemoglobin is a better carrier of CO2 than oxyhemoglobin is; consequently at the tissue where hemoglobin is losing its oxygen it is becoming a more efficient CO2 transporter. This is known as the Haldane effect.
Transport as Dissolved CO2 (About 7 Percent)
A little CO2 combines with water to produce carbonic acid, the dissociated hydrogen form that must be buffered by plasma proteins, such as albumin.
Transport as Bicarbonate (About 70 Percent)
Seventy percent of the CO2 enters red blood cells, and once inside a familiar reaction occurs (equation 16.2.1). The CO2 binds with water in the cytoplasm, producing carbonic acid, which then dissociates into a hydrogen ion and a bicarbonate ion.
This reversible reaction is accelerated by the enzyme carbonic anhydrase and is driven rapidly to the right by the high concentration of CO2 at the tissue.
The hydrogen ion produced helps shift the oxygen saturation curve to the right and so promotes further release of oxygen to the tissue. Hemoglobin then serves yet another purpose by buffering the proton with its polypeptide chains. Deoxyhemoglobin is a better proton acceptor than oxyhemoglobin, so as the hemoglobin loses its oxygen at the tissue it becomes a better pH buffer. This reduces the amount of hydrogen ion on the right side of our equation and moves the equation to the right, promoting the conversion of more CO2.
\[CO_2 + H_2O \leftrightarrow H_2CO_3 \leftrightarrow H^+ + HCO_3- \nonumber \]
High concentrations of CO2 at the tissue push this equation right to produce bicarbonate.
The bicarbonate ion is pumped out of the cell, but without intervention this would leave the inside of the cell too positively charged as the negative charge of the bicarbonate is lost. To maintain electroneutrality the bicarbonate is exchanged for a chloride ion; this process is referred to as the chloride shift. The formation of bicarbonate at the tissue is summarized in figure 16.9.
Figure 16.9: Formation of bicarbonate at the tissue.
The CO2 now travels through the bloodstream as bicarbonate toward the lungs. At the lungs the process is basically reversed. The partial pressure of CO2 at the lungs is low; consequently our equation is driven toward the left-hand side as CO2 leaves toward the low alveolar PCO2 (equation 16.2.2).
\[CO_2 + H_2O \leftrightarrow H_2CO_3 \leftrightarrow H^+ + HCO_3- \nonumber \]
←
High bicarbonate and low CO2 at the lung force the equation leftward.
The high alveolar PO2 also promotes the leftward movement—binding of oxygen to hemoglobin makes hemoglobin a less effective proton binder so it loses the proton and raises the amount of substrate on the right-hand side and thereby promotes reformation of CO2. The Haldane effect is also reversed—as hemoglobin gains oxygen at the lung it loses its affinity for CO2 and releases it into the plasma. This raises plasma PCO2 and promotes diffusion of CO2 into the alveoli for expulsion.
Likewise the chloride shift is reversed and bicarbonate reenters the cell as chloride is pumped back out.
All these moves help promote the right-to-left direction of our now infamous equation and the re-forming of CO2. Alveolar ventilation gets rid of the re-formed CO2 to the atmosphere, maintaining the alveolar PCO2 at relatively low levels and the direction of the equation right-to-left. The reformation of CO2 at the lungs is summarized in figure 16.10.
The CO2 "Dissociation" Curve
So, for want of a better name, we can also draw a CO2 dissociation or saturation curve, as is shown in figure 16.11. The graph shows the CO2 concentration in blood across a wide range of PCO2 and shows the effect of Hb O2 saturation on CO2 carriage. The CO2 dissociation curve is unlike the oxygen saturation curve and is virtually linear (i.e., the higher the PCO2, the higher the CO2 content of the blood); there is no plateau to the curve as we saw with O2 transport. The ramification of this is that the lower the alveolar PCO2, the lower the blood PCO2, and the higher the alveolar PCO2, the higher the blood PCO2. It is a very simple relationship that ends with the obvious statement that the more you breathe, the lower arterial CO2 becomes. It is worth reminding ourselves here that this is not a relationship seen with oxygen that is limited by the capacity of hemoglobin (breathing more does not necessarily result in more oxygen in the bloodstream). The other aspect to note here is the effect of hemoglobin’s oxygen saturation on carbon dioxide carriage. This has clinical ramifications, so we will look at this more closely.
When deoxygenated, hemoglobin’s structure promotes binding of CO2 and buffering of protons by the polypeptide chains. So when O2 saturation is zero, the CO2 and proton carrying capability of Hb is high. As already mentioned, this means that when Hb is in its deoxygenated form at the tissue, its CO2 carrying ability is increased.
Figure 16.10: Reformation of CO2 at the lungs.
Figure 16.11: CO2 dissociation curve.
When we get to the lung, however, the Hb is exposed to the high alveolar PO2 and oxygen binds to the heme sites and becomes saturated; this causes a conformational change, and the CO2 and proton carrying ability is reduced. So conveniently CO2 release is promoted at the lung.
Summary
Although CO2 is highly soluble, very little of it can be transported as dissolved CO2 in plasma because of its effect on pH. The majority is converted to bicarbonate in red blood cells and transported in plasma, while about 25 percent is transported bound to hemoglobin.
References, Resources, and Further Reading
Text
Levitsky, Michael G. "Chapter 7: Transport of Oxygen and Carbon Dioxide in the Blood." In Pulmonary Physiology, 9th ed. New York: McGraw Hill Education, 2018.
West, John B. "Chapter 6: Gas Transport by the Blood—How Gases Are Moved to the Peripheral Tissues." In Respiratory Physiology: The Essentials, 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams and Wilkins, 2012.
Widdicombe, John G., and Andrew S. Davis. "Chapter 6." In Respiratory Physiology. Baltimore: University Park Press, 1983.
Figures
Figure 16.1: Basic structure of hemoglobin. OpenStax College. 2013. CC BY 3.0. https://commons.wikimedia.org/wiki/File:1904_Hemoglobin.jpg [added polypeptide chain]
Figure 16.2: Hemoglobin saturation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.2_20220125
Figure 16.3: The hemoglobin saturation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/15.1-needs-numbering
Figure 16.4: Effect of temperature on the saturation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.4_20220125
Figure 16.5: Effect of PCO2 on the saturation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.5_20220125
Figure 16.6: Effect of pH on the saturation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.6_20220125
Figure 16.7: Oxygen carriage. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.7_20220125
Figure 16.8: Compartment of blood oxygen content. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/16.8_20220125
Figure 16.9: Formation of bicarbonate at the tissue. Grey, Kindred. 2022. CC BY-SA 3.0. Added Erythrocyte deoxy by Rogeriopfm from WikimediaCommons [added text around image]. CC BY-SA 3.0. https://archive.org/details/15.2-needs-numbering
Figure 16.10: Reformation of CO2 at the lungs. Grey, Kindred. 2022. CC BY-SA 3.0. Added Erythrocyte deoxy by Rogeriopfm from WikimediaCommons [added text around image]. CC BY-SA 3.0. https://archive.org/details/15.3
Figure 16.11: CO2 dissociation curve. Grey, Kindred. 2022. CC BY 4.0. https://archive.org/details/15.4_20220125