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In a previous post, we talked about oxygen in connection with pregnancy and COVID-19, but oxygen is only half of the story of breathing. Just as the lungs serve as a portal for oxygen to enter the bloodstream from the air, these organs of breathing also serve as a portal for another gas, carbon dioxide, to exit the blood and go into the air around you. The basic idea that we take in oxygen from air that we inhale in order to support our cells and exhale carbon dioxide as a waste product is something that we humans learned less than 300 years ago. From Antiquity up to about the 17th century, doctors had little idea what the lungs do. One popular idea was that lungs functioned simply to cool the heart. They also had no idea at all that air is a mixture of gases. Clinging to ideas from the ancient Greeks, doctors thought about health and disease in terms of a proper versus improper balance between four “humors” that they believed comprised everything in the body: blood, phlegm, yellow bile, and black bile. Similarly, they thought of the air as one of four basic “elements” that combined in various proportions to produce all matter, the other “elements” being fire, water, and earth. The concept of the four elements dated back to the Greek philosopher Empedocles, but Empedocles also performed an experiment that proved for the first time that air was a thing that took up space.
During the 17th century, the anatomist William Harvey proved what a tiny handful of researchers had been suggesting since the Middle Ages, but that most physicians believed was false: that blood from the right side of the heart passed through the lungs before entering the left side of the heart. In the middle of the next century, the Scottish researcher Joseph Black produced carbon dioxide from limestone and realized that the same gas was present in air exhaled from the lungs. He didn’t call the gas carbon dioxide, because the science of chemistry, based on the idea that things are made of molecules and atoms, would not come to life, but for the work of a French researcher a generation later, Antoine Lavoisier. Building on a discovery of the English researcher, Joseph Priestley, of how to generate oxygen in pure form, Lavoisier gave oxygen its name, demonstrated that oxygen and hydrogen combined explosively to produce water, and really was the first person to understand what the gases comprising air actually were. Thanks to Black, Priestley, and Lavoisier, humans quickly came to understand that oxygen gas consists of molecules, each made of two oxygen atoms (so we call it O2), and that carbon dioxide consists of molecules, each made of one carbon atom plus two oxygen atoms (so we call it CO2). Scientists also figured out that plants, algae, and certain bacteria could transform CO2 into food, while splitting up molecules of water (H2O), thus releasing O2 into the air that we breathe.
When you are pregnant, the O2 that you take in through your lungs must reach the blood of the fetus, while CO2 produced in the cells of the fetus must move from the fetal blood to your blood, so that you can release it through your lungs. The exchange of both gases occurs in the placenta, in a special system of capillaries (microscopic blood vessels) that bring material blood into close proximity with fetal blood. Most of the oxygen in blood is carried by a protein called hemoglobin, which fills red blood cells. Mostly because oxygen is attracted to fetal hemoglobin a little more strongly than it is attracted to adult hemoglobin, oxygen moves from the maternal blood into the fetal blood. At the same time, CO2 moves from the fetal blood to the maternal blood for a few reasons. The main reason is that the mother’s lungs continuously remove CO2 from her own blood, creating an opportunity for fetal CO2 to move to where it is less abundant –just like if you pour a salty liquid or a sweet liquid into water, the saltiness or the sweetness spreads out. While inside the blood, CO2 makes the blood more acidic, which means that the mother’s lungs are vital to controlling both the acidity of her own blood and of the blood of her fetus.
While an inadequate supply of oxygen through the lungs leads to what doctors call cyanosis, a bluish discoloration of the skin, the rate and depth of breathing is controlled mostly by the amount of CO2 in your blood. If you are healthy and doing some activity, such as running or walking up flights of stairs, the increased production of CO2 stimulates your breathing in a way that gets enough O2 into your blood to meet increased demands of your muscle cells. Consequently, you do not become cyanotic. Furthermore, if you place a device called a pulse oximeter on your finger, it will show that the hemoglobin in your red blood cells is carrying close to 100 percent of the O2 that it is capable of carrying. Another way of saying this is that your oxygen saturation (O2 sat) is almost 100 percent. While healthy people often have an O2 sat of 98 to 100 percent, any reading of 95 percent and higher is considered normal.
Now, when it comes to COVID-19, in many cases, the O2 sat of people with moderate disease drops way down into the low 80s, or sometimes much lower, suggesting that their lungs are not doing a good job getting O2 into the blood. Even so, their lungs are still doing a good job removing CO2 from the body. Because this makes the CO2 level in the blood close to normal, the drive to increase breathing is not stimulated and they don’t even have a sensation of breathing difficulty. Sometimes this phenomenon is called silent hypoxia, meaning that oxygen levels coming in through the lungs are low, without triggering any kind of alarm, if the person is not wearing a pulse oximeter. Since silent hypoxia also may not trigger any discomfort, sometimes silent hypoxia called happy hypoxia.
Silent hypoxia has been documented in several medical conditions, but it has been particularly noteworthy in COVID-19. In some ways, silent hypoxia is baffling, given that about 10 percent of the CO2 transported in the blood is carried by hemoglobin. When hemoglobin comes into contact with elevated levels of oxygen, such as in the lungs or in the placenta, it is triggered to let go of the CO2 that it has been carrying. This is called the Haldane effect, named for John Scott Haldane, one of the great pioneers of physiology in the early 20th century. If the lungs of people with COVID-19 are exhaling normal quantities of CO2, then, based on the Haldane effect, we should expect that good amounts of oxygen are entering capillaries of the lungs’ air sacs. However, oxygen is not entering the blood adequately in many COVID-19 patients. Researchers are thus debating the nature of the abnormality that occurs in the lungs with this disease.
But the problems in COVID-19 are not limited to the lungs. Based on what is known so far, although infection with SARS-CoV2 (the virus that causes COVID-19) certainly harms the lungs in many people, scientists are finding that the lungs furthermore serve as the main port of entry for the virus into the body. The virus enters lung cells utilizing a protein on the cell surface called the ACE-2 receptor, but lung cells are not the only cells that have this receptor. Rather, the ACE-2 is present on many other types of body cells, and furthermore, the virus doesn’t do harm only by using ACE-2 to getting into cells. ACE-2 isn’t sitting on cells waiting around for a virus. ACE-2 has a job, which the virus prevents it from doing. In connection both with infecting cells and taking ACE-2 away from its job, it is now known that the SARS-CoV2 has a range of effects including the formation of blood clots and problems that can occur in various organs –organs that also are harmed in those who cannot get enough oxygen into their blood on account of the lung problems. Consequently, the COVID-19 disease process is characterized by a particularly high level of complexity, and so we should expect that the disease will continue to surprise us.