Carbon Dioxide Transport

1. Carbon Dioxide in the Arterial Blood
2. The pH of the Plasma
3. Production and Control of Hydrogen Carbonate Ions
4. Buffers
5. Carbon Dioxide in the Venous Blood
6. Summary of Carbon Dioxide Transport
7. Quiz

• Carbon dioxide is about 20 times more soluble than oxygen. Arterial blood contains about 21.1 mmol/L (millimoles per litre) of total carbon dioxide, mostly as hydrogen carbonate ions, compared with 8.8 mmol/L of oxygen, mostly bound to haemoglobin.
• Carbon dioxide reacts with water molecules to produce hydrogen ions and hydrogen carbonate ions (also called bicarbonate ions).
• The pH of the plasma depends on the ratio of hydrogen carbonate to dissolved carbon dioxide. The concentration of dissolved carbon dioxide depends on the partial pressure of carbon dioxide in the blood (the share of the total gas pressure that is due to carbon dioxide).
• There is a high concentration of hydrogen carbonate ions in the plasma. These do not stop dissolved carbon dioxide reacting with water. They act as a buffer, and the ratio of hydrogen carbonate to dissolved carbon dioxide keeps the pH of the plasma slightly alkaline (pH 7.35 - 7.45).
• The reaction between carbon dioxide and water is sped up by the enzyme carbonic anhydrase in red blood cells (erythrocytes). The hydrogen ions react with haemoglobin, whilst the hydrogen carbonate ions move into the plasma of the blood.
• Hydrogen carbonate ions are able to react with acids that the body has produced (like lactic acid), and the carbon dioxide produced is breathed out, resulting in minimal changes to the pH of the plasma.
• There are three forms in which carbon dioxide can be transported around the body: dissolved in the plasma, as hydrogen carbonate ions, and as carbamino compounds (carbon dioxide bound to haemoglobin).

Carbon dioxide is more soluble than oxygen (about 20 times more). Arterial blood contains about 21.1 mmol/L of total carbon dioxide, mostly as hydrogen carbonate ions, compared with 8.8 mmol/L of oxygen, mostly bound to haemoglobin. The carbon dioxide in the blood reacts with the water and haemoglobin molecules to allow this large amount of carbon dioxide to be carried. It is important to know that carbon dioxide binds to a different site to oxygen molecules on the haemoglobin molecule.

Carbon Dioxide in Arterial Blood

Arterial blood contains a relatively high concentration of carbon dioxide. This seems almost wrong, because carbon dioxide is seen as a waste product that would only be present in venous blood. However, carbon dioxide has an important role in controlling the pH of the blood, which is necessary to prevent the denaturation of proteins (their loss of shape and function) in the blood.

Carbon dioxide dissolves in water and once dissolved, the carbon dioxide molecules are able to react with the water molecules to form carbonic acid (H₂CO₃). Carbonic acid quickly dissociates into hydrogen ions (H⁺) and hydrogen carbonate ions (HCO₃^-). The reaction described is reversible, meaning it is dependent on the concentration of reactants (carbon dioxide and water) and products (hydrogen ions and hydrogen carbonate ions).

Diagram - The reaction between carbon dioxide and water to form hydrogen and hydrogen carbonate ions

SimpleMed original by Dr. Peter Parkinson

The pH of the Plasma

The overall pH of the plasma of the blood depends upon the concentration of dissolved carbon dioxide and on the concentration of hydrogen carbonate ions (the Henderson-Hasselbalch equation below shows how the two combine). Taking dissolved carbon dioxide first, a large amount of dissolved carbon dioxide will push the reaction to the right hand-side (meaning more H⁺ and HCO₃^- ions are produced). A high concentration of H⁺ and HCO₃^- ions will push the reaction to the left hand-side (increasing the amount of CO₂ produced).

The concentration of carbon dioxide dissolved in the plasma depends on the partial pressure of carbon dioxide of the blood (pCO₂). This in turn depends on how much carbon dioxide is present in the alveoli (the partial pressure of carbon dioxide in the alveoli). The ventilation rate (how quickly and deeply we breathe) controls this.

If the pCO₂ increases, the pH of the plasma will decrease and become more acidic because this pushes the reaction to the right, which produces more H⁺ ions. However, if the pCO₂ decreases, the pH of the plasma will increase and become more alkaline. This is because a lower pCO₂ pushes the reaction to the left, which reduces the amount of H⁺ ions.

Plasma contains around 25 mmol/L of hydrogen carbonate ions. Hydrogen carbonate participates in the reversible carbon dioxide/carbonic acid buffer system; it does not prevent carbon dioxide from reacting with water or stop further carbon dioxide dissolving. The concentration of dissolved carbon dioxide depends on its partial pressure and solubility. Plasma pH depends on the balance between hydrogen carbonate and dissolved carbon dioxide, as described by the Henderson-Hasselbalch equation below.

Diagram - The reversible carbon dioxide/hydrogen carbonate buffer equilibrium. The arrows illustrate the influence of reactant and product concentrations; hydrogen carbonate does not prevent carbon dioxide reacting with water or dissolving in plasma.

SimpleMed original by Dr. Peter Parkinson

It is possible to calculate the pH of the plasma by using the Henderson-Hasselbalch equation. The equation uses the values of pCO₂ and concentration of HCO₃^- ions. 

Henderson-Hasselbalch Equation: pH = 6.1 + log₁₀([HCO₃^-] / (0.03 x pCO₂)). In this form, [HCO₃^-] is in mmol/L and pCO₂ must be in millimetres of mercury (mmHg), not kilopascals (kPa).

The value for pK is a measure of how strong an acid is (the lower the pK, the stronger the acid). For the carbon dioxide and hydrogen carbonate buffer system, the pK is about 6.1 at normal body temperature (37°C).

Multiplying pCO₂ in mmHg by 0.03 converts it to the concentration of dissolved carbon dioxide in mmol/L at 37°C. If a pressure is reported in kPa, multiply it by 7.5 to convert it to mmHg before using this coefficient.

It is also important to note that in this equation, HCO₃^- is divided by CO₂. This means that if HCO₃^- increases, the pH will increase, but if CO₂ increases, the pH will decrease. A fall in pH when CO₂ rises also makes sense, because CO₂ dissolves to produce H⁺ ions. 

While an understanding of this equation is important for skills like interpretation of an arterial blood gas (a blood test that measures oxygen, carbon dioxide and pH in arterial blood), in clinical practice the analyser measures the pH and pCO₂ directly and calculates the hydrogen carbonate from them.

Production and Control of Hydrogen Carbonate Ions

Within the erythrocytes, carbon dioxide reacts with water molecules within the cytoplasm of the cell to form hydrogen ions and hydrogen carbonate ions as shown above. This reaction is sped up by the action of the enzyme carbonic anhydrase.

H⁺ ions bind to haemoglobin inside the erythrocyte, reducing their free concentration. HCO₃^- ions are exported into plasma through the chloride-bicarbonate exchanger (a membrane protein that swaps bicarbonate out of the cell for chloride in). Buffering hydrogen ions and exporting bicarbonate favour continued conversion of carbon dioxide into bicarbonate. Bound hydrogen remains inside the cell, and some free H⁺ and HCO₃^- ions always remain, so the reaction is pulled forward but never runs to completion.

Diagram - The production of hydrogen carbonate ions in erythrocytes

SimpleMed original by Dr. Peter Parkinson

The concentration of HCO₃^- ions produced in this way depends on the concentration of H⁺ ions that bind to haemoglobin. The kidneys are responsible for controlling excretion of H⁺ ions in urine.

Overall, pH of the plasma depends on the pCO₂ and the concentration of HCO₃^- ions.

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