Carbon Dioxide Transport in the Blood

What Is Carbon Dioxide Transport?

Carbon dioxide transport is the carriage of carbon dioxide by the blood from the body's cells, where it is produced, to the lungs, where it is released into the air and exhaled. It is the mirror image of oxygen transport, which carries oxygen in the opposite direction on the same journey.

Every cell makes carbon dioxide as it breaks down glucose and fats for energy in cellular respiration. A resting adult produces roughly 200 milliliters of carbon dioxide every minute, and much more during exercise. If it were not removed, it would combine with water to form acid and quickly lower the pH of the body fluids. The blood therefore has to pick it up continuously and deliver it to the lungs, where gas exchange passes it into the alveoli.

Why the blood needs special carrier forms

Carbon dioxide dissolves in water about 20 times more readily than oxygen, but even so, simple solution could carry only a small part of what the body makes. Most of it is therefore converted to other forms: bicarbonate ions and carbamino compounds. These forms let each 100 milliliters of blood hold about 50 milliliters of carbon dioxide, far more than dissolved gas alone, and release it again in the lungs within the second or so a red blood cell spends there.

Explained simply

Think of carbon dioxide as trash from your cells. A little floats loose in the blood, some is clipped onto the outside of red blood cells' hemoglobin, and most is turned into a different form, bicarbonate, that dissolves easily in the watery plasma. When the blood reaches the lungs, everything is turned back into carbon dioxide gas and breathed out.

What Ways Is Carbon Dioxide Transported in the Blood?

Carbon dioxide is transported in the blood in three ways: as bicarbonate ions in the plasma (about 70%), as carbamino compounds bound to hemoglobin and plasma proteins (about 20 to 23%), and as dissolved carbon dioxide (about 7 to 10%). These are typical textbook shares for venous blood, and they shift a little with activity and oxygen level.

1. Dissolved in plasma (about 7 to 10%)

A small amount of carbon dioxide simply dissolves in the plasma, like the gas in a soft drink. The amount depends on the partial pressure of carbon dioxide and its solubility. Although it is the smallest share, dissolved carbon dioxide matters most for sensing, because it sets the partial pressure that the respiratory chemoreceptors respond to, and it is the form that actually diffuses across membranes.

2. Bound to hemoglobin as carbaminohemoglobin (about 20 to 23%)

Carbon dioxide can attach to the free amino groups at the ends of the protein chains of hemoglobin, forming carbaminohemoglobin. It binds to the globin protein, not to the iron-containing heme groups where oxygen binds, so the two gases do not compete for the same site. Plasma proteins form carbamino compounds too, but in much smaller amounts. Deoxygenated hemoglobin binds carbon dioxide more readily than oxygenated hemoglobin, which is one reason venous blood carries more.

3. As bicarbonate ions (about 70%)

Most carbon dioxide enters red blood cells and is converted into bicarbonate ions, which then move out into the plasma. This is the main route because bicarbonate is very soluble and the conversion is extremely fast inside red cells. The next two sections explain how bicarbonate is made and why chloride ions move in return.

How Does Carbon Dioxide Become Bicarbonate?

Carbon dioxide becomes bicarbonate when it combines with water to form carbonic acid, which then splits into a hydrogen ion and a bicarbonate ion; inside red blood cells the first step is speeded up enormously by the enzyme carbonic anhydrase. The reaction can be written as:

CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃^-

The double arrows matter: the same reaction runs forward in the tissues, where carbon dioxide is plentiful, and backward in the lungs, where carbon dioxide is being removed. Which way it runs depends only on the concentrations on each side.

The role of carbonic anhydrase

In plasma, carbon dioxide combines with water only slowly, because plasma has almost no carbonic anhydrase. Red blood cells are packed with it, and it is one of the fastest enzymes known, speeding the reaction by thousands of times. That is why bicarbonate is made almost entirely inside red cells, even though most of it ends up carried in the plasma.

What happens to the hydrogen ions

Each bicarbonate ion made also releases a hydrogen ion, which on its own would make the blood much more acidic. Most of these hydrogen ions are picked up by hemoglobin, which acts as a buffer. Hemoglobin that has just given up its oxygen in the tissues is a better buffer than oxygenated hemoglobin, so the unloading of oxygen and the loading of carbon dioxide help each other. This binding of hydrogen ions also lowers hemoglobin's grip on oxygen, the Bohr effect.

What Is the Chloride Shift?

The chloride shift is the exchange of bicarbonate ions leaving red blood cells for chloride ions entering them, which keeps the electrical charge of the cell balanced while carbon dioxide is converted to bicarbonate. It is also called the Hamburger shift, after the Dutch physiologist Hartog Jakob Hamburger, who first described it.

Bicarbonate builds up inside the red cell as carbonic anhydrase works, so it diffuses out into the plasma, where it is carried to the lungs. If negative ions simply left the cell, the inside would become positively charged and the process would stall. Instead, a membrane protein called band 3, also known as anion exchanger 1, swaps one bicarbonate ion out for one chloride ion in. Band 3 is one of the most abundant proteins in the red cell membrane, so the exchange is very fast.

Effects of the chloride shift

• Venous red blood cells contain more chloride than arterial ones, and the plasma of venous blood contains a little less.
• The extra ions inside venous red cells draw in some water, so they are slightly larger than arterial red cells.
• Removing bicarbonate from the red cell keeps the carbonic anhydrase reaction running forward, so more carbon dioxide can be loaded.

The reverse chloride shift in the lungs

In the lung capillaries everything runs the other way. Bicarbonate re-enters the red cells in exchange for chloride, which leaves for the plasma. Inside the cell, bicarbonate combines with hydrogen ions released from hemoglobin to form carbonic acid, and carbonic anhydrase turns it back into water and carbon dioxide, which diffuses into the alveoli.

Carbon Dioxide Transport Process: What Happens Step by Step?

The carbon dioxide transport process has two halves: loading in the tissue capillaries, where carbon dioxide enters the blood and is converted to carrier forms, and unloading in the lung capillaries, where the carrier forms are turned back into gas and exhaled. The steps below follow one red blood cell around the circuit.

Loading in the tissues

1. Diffusion out of the cell. Carbon dioxide made in the mitochondria diffuses out of the tissue cell, through the fluid around it and into a systemic capillary, down its partial pressure gradient.
2. Some stays dissolved. A small share remains dissolved in the plasma.
3. Entry into red cells. Most diffuses into red blood cells, where some binds to hemoglobin as carbaminohemoglobin.
4. Conversion to bicarbonate. Carbonic anhydrase turns the rest into carbonic acid, which splits into hydrogen ions and bicarbonate.
5. Buffering. Hemoglobin, which is releasing oxygen at the same time, binds most of the hydrogen ions.
6. Chloride shift. Bicarbonate leaves the red cell for the plasma in exchange for chloride.

Unloading in the lungs

1. Diffusion into the alveoli. Dissolved carbon dioxide diffuses from the plasma across the respiratory membrane into the alveoli, lowering the plasma level.
2. Release from hemoglobin. As hemoglobin picks up oxygen, it releases its carbon dioxide and hydrogen ions.
3. Reverse chloride shift. Bicarbonate re-enters red cells as chloride leaves.
4. Back to gas. Bicarbonate and hydrogen ions form carbonic acid, which carbonic anhydrase turns into carbon dioxide and water.
5. Exhalation. The carbon dioxide diffuses into the alveoli and leaves the body with the next breath out, as described on our inhalation and exhalation page.

Blood flows from the tissues to the lungs through the veins, the right side of the heart and the pulmonary arteries, the route described on our pulmonary circulation page.

How Does Oxygen Affect Carbon Dioxide Transport?

Oxygen affects carbon dioxide transport through the Haldane effect: hemoglobin that has released its oxygen can carry more carbon dioxide and hydrogen ions, while hemoglobin that is loading oxygen releases them. This makes the blood pick up carbon dioxide better in the tissues and give it up better in the lungs.

The effect works in two ways. Deoxygenated hemoglobin forms carbaminohemoglobin more easily, and it binds hydrogen ions more strongly, which pulls the carbonic anhydrase reaction toward more bicarbonate. When the blood reaches the lungs and hemoglobin fills with oxygen, both effects reverse, pushing carbon dioxide out of the blood. Our glossary entry on the Haldane effect explains it in more depth.

Haldane effect and Bohr effect together

The Haldane effect describes how oxygen changes carbon dioxide carriage, while the Bohr effect describes the reverse: how carbon dioxide and acid change oxygen carriage, shifting the oxygen-hemoglobin dissociation curve to the right. In the tissues, carbon dioxide helps unload oxygen and oxygen loss helps load carbon dioxide; in the lungs, both effects run backward. The two gases therefore help each other move in the right direction at both ends of the trip.

The carbon dioxide dissociation curve

Unlike the S-shaped curve for oxygen, the curve relating blood carbon dioxide content to its partial pressure is fairly straight across the normal range and does not level off. There are in fact two curves, one for oxygenated and one for deoxygenated blood, and the gap between them is the Haldane effect. Because the curve stays steep, small changes in breathing change blood carbon dioxide noticeably.

How Does Carbon Dioxide Transport Affect Blood pH?

Carbon dioxide transport affects blood pH because every molecule converted to bicarbonate releases a hydrogen ion, so the more carbon dioxide the blood holds, the more acidic it tends to be. The lungs and kidneys together keep arterial pH in a narrow range, about 7.35 to 7.45.

The bicarbonate made during carbon dioxide transport is also the body's most important chemical buffer in the blood. The balance between dissolved carbon dioxide and bicarbonate sets the pH, which gives the body two levers: the lungs adjust carbon dioxide within minutes by changing ventilation, and the kidneys adjust bicarbonate over hours to days. Venous blood, which carries more carbon dioxide, is therefore slightly more acidic than arterial blood.

When breathing changes

• Breathing too little lets carbon dioxide build up, so the blood becomes more acidic, a state called respiratory acidosis.
• Breathing too much removes extra carbon dioxide, so the blood becomes more alkaline, called respiratory alkalosis.
• Acid from other sources, such as a buildup of lactic acid during very hard exercise, uses up bicarbonate, and faster breathing removes carbon dioxide to limit the fall in pH.

This link between carbon dioxide and pH is why carbon dioxide is the main signal used by the control of breathing, and it is a central part of how the respiratory system maintains homeostasis. Our page on hyperventilation and hypoventilation describes both extremes.

Common Conditions That Affect Carbon Dioxide Transport

Carbon dioxide transport is disturbed mainly when the lungs cannot remove carbon dioxide fast enough, when breathing is too fast or too slow for the body's needs, or when the acid-base balance of the blood is upset. Our respiratory diseases section covers lung conditions in more depth, and anyone with breathing symptoms should see a doctor.

• COPD: in severe cases, damaged airways and alveoli limit how much carbon dioxide can be breathed out, and its level in the blood rises over time.
• Hypoventilation: slow or shallow breathing from drug effects, weakness of the breathing muscles or severe obesity lets carbon dioxide accumulate.
• Sleep apnea: repeated pauses in breathing during sleep cause short rises in carbon dioxide and falls in oxygen.
• Hyperventilation: breathing faster than needed, for example during anxiety, lowers blood carbon dioxide and can cause tingling and lightheadedness.
• Asthma attacks: narrowed airways make breathing out harder; a rising carbon dioxide level during a severe attack is a warning sign doctors watch for.
• Ventilation-perfusion mismatch: when air and blood flow are poorly matched in parts of the lung, both oxygen uptake and carbon dioxide removal suffer; see the ventilation-perfusion ratio.

Doctors measure carbon dioxide in arterial blood with a blood gas test, and in exhaled air with a sensor called a capnograph.