The Gases of Breathing Part 2: Carbon Dioxide

While oxygen receives the most attention as the gas that is vital to life, the presence of carbon dioxide is essential in the body for oxygen’s proper utilization. CO2 gets a bad rap in a lot of discussions, sometimes even being called a pollutant. What is implied by this term is that CO2 is harmful to life, but the truth is that CO2 is essential for the proper functioning of our bodies, to say nothing of the plants which absorb CO2 to create sugars. CO2 is essential to homeostasis.

CO2 is produced in our bodies as a biproduct of the metabolism of glucose and fats in what are called mitochondria, which are the power plants of our cells. The majority of the mass that makes up the energy stores in our body leaves our body as CO2 once it is burned, so when we go on a fat loss diet we are literally breathing out the weight we are losing (and before you get any bright ideas just let me say that over-breathing does not help you lose weight!)

One of the major ways that CO2 affects the body is through its influence on blood pH. When CO2 dissolves in blood as a gas, a portion of it bonds with water to synthesize carbonic acid:
CO2+H2O⟶H2CO3
As the term acid implies, the compound lowers the pH. It does this by dissociating into bicarbonate and hydrogen ions, the concentration of latter of which is inversely proportional to pH:
H2CO3⟶HCO3−+H+

The acidity of a fluid like blood plasma has a large impact on the functioning and even the structure of proteins, hence why blood pH is so tightly monitored by the body as a homeostatic parameter. It is through the changes to pH brought about by the concentration of CO2 that CO2 acts on the functioning of the body.

The two major ways CO2 affects the body via changes in pH is by changing (1) the ability of hemoglobin to bind oxygen, and (2) to affect the dilation or construction of blood vessels. Both of these have significant impacts on the ability of tissues themselves to oxygenate.

CO2 and Hemoglobin’s affinity for Oxygen: The Bohr Effect

As a biproduct of metabolism, CO2 concentration in tissues and blood is a marker of the metabolic demand that is being placed on those tissues. Say for example if you are running up a hill. The production of CO2 in the body increases drastically in the legs. Even with the circulation of the blood, the concentration, sometimes called the partial pressure, of CO2 will continue to be higher in the legs insofar as they are working and spending energy. The increase in CO2's concentration causes more CO2 to convert with water to carbonic acid to lower the pH.

Hemoglobin is such a protein affected by pH. Hemoglobin binds oxygen and must release it at the opportune times, i.e. in tissues that are metabolically demanding and requiring more oxygen. If hemoglobin just bound oxygen and held onto it forever, astonishingly little oxygen would be freed up and available to feed our tissues. Hemoglobin releases its oxygen intelligently because as a protein it is sensitive to changes in pH. Lower pH, or higher acidity, driven for example by excess dissolution of CO2 into the blood as carbonic acid, is what causes hemoglobin to hold onto oxygen more loosely. This results in oxygen being released at a higher rate in capillaries where the pH has been driven downward by excess CO2 production in tissues where there greater metabolic demand.

This is called the Bohr Effect, named after the scientist who discovered hemoglobin’s pH-dependent release of oxygen in 1904.

CO2 and Vasodilation

Another role CO2 plays in the body is to relax the muscles which exist around blood vessels, causing the blood vessels to accept greater volumes of blood (i.e. greater perfusion) and therefore greater oxygenation of surrounding tissues. This is another effect mediated by blood pH.

To talk about vasodilation I first need to talk about muscles in general, with particular respect paid to calcium (Ca2+) ions in the blood.

Muscle cells function by maintaining a contrasting concentration of electrolytes within the cell vs outside the cell. On the membrane of muscle cells there are protein pumps which move sodium ions (Na+) out of the cell and potassium ions (K+) into the cell. It does this at a specific ratio to create an electrical potential across the membrane of muscle cells. When a nerve signal reaches a muscle, a chemical messenger called acetylcholine is released from the neuron, which binds to sodium pumps and switches them on, causing sodium to flood the muscle cell and the membrane potential to become progressively depolarized, electrically speaking.

Once a certain threshold is reached, the electrical depolarization of the membrane triggers voltage-gated sodium channels to open, and the muscle cell gets flooded with sodium. This causes calcium ions (Ca2+) stored in compartments in muscle cells called sarcoplasmic reticulum to release into the cell. The presence of calcium ions in muscle cells is what triggers motor proteins to recruit and contract the muscle fiber.

While a high concentration of Ca2+ in the cell triggers muscle contractions, its presence in the extracellular environment, such as the interstitial fluids, has an inhibitory effect on muscle contractions. As a positive ion it also contributes to the electrical potential across the cellular membrane of muscle fibres, and with higher Ca2+ concentrations increasing the amount of sodium needing to cross the cellular membrane to depolarize the membrane sufficiently to trigger a muscle contraction. Conversely, lower levels of Ca2+ in the blood decreases the threshold of activation for voltage-gated channels involved in depolarizing muscle cell membranes. What this means is that higher Ca2+ concentrations dampen the excitability of neurons and muscle cells, while lower Ca2+ concentrations increase the excitability, causing them to be more likely to fire.

Calcium exists in the bloodstream either free-floating as Ca2+ ions or bound to albumin. Albumin’s affinity for binding calcium is regulated by blood pH, holding onto calcium more tightly at higher pH levels. When a tissue or organ, such as the brain, is metabolically active more CO2 is released from the tissues. This lowers the pH, increases the release of Ca2+ from albumin into the blood, and dampens the excitability of the smooth muscles around blood vessels. This causes the vascular muscles to relax, decrease blood pressure, and cause more blood to flow through the area, resulting in rapid release of oxygen in that area (also prompted by the lower pH).

Parting Thoughts

CO2’s constant production in the body as a metabolic biproduct is utilized by the body to determine areas of higher metabolic demand in the body, which impacts the functioning of the circulatory system (heart, blood, and blood vessels) to optimize the release of oxygen to tissues where it is needed most.

Changes in the body due to a variety of conditions, including breathing pattern disorders, can contribute to states of respiratory acidosis or alkalosis, where CO2 is either retained for longer than usual or removed more rapidly than usual respectively. This will be the subject of the next post.