In my last posting, we discussed the adaptive response to lack of oxygen in wounds and in solid tumors. These are situations in which only a small area of the body is affected, while the oxygen supply to the rest of the body remains normal. There are situations, however, in which the whole body suffers from lack of adequate oxygen supply. The most common is emphysema, a chronic lung condition often related to cigarette smoking.


The structure of our airway

Our airway looks like a tree. The trunk, the main windpipe, is called the trachea. It branches into smaller caliber branches, or bronchi, and those, in turn, give rise to progressively smaller branches called bronchioles. The last and smallest twig, the terminal bronchiole, opens into an air sack (alveolus) which looks like a tiny balloon. The alveolus is made up of a very thin wall enclosing an air space. Thousands of these air sacks (alveoli) make up the lung.

When we inhale, our chest expands, the lungs expand, and air rushes into the alveoli. Oxygen is then taken up by the blood vessels (capillaries) that course through the walls of the alveoli and carbon dioxide is released from the blood into the alveolar airspace. When we exhale, the elastic alveolar walls contract, chest volume decreases, and carbon dioxide is expelled outside of our body. Think of a balloon letting out air through its elastic contraction.


What is emphysema?

To understand what happens to the emphysematous lung, think of a balloon that has seen better days before losing its elasticity. Air is not expelled as forcefully and completely as before; in fact, a relatively large volume of air remains within the balloon.

When a disease process destroys the all-important alveolar wall, several things happen. Adjacent alveoli whose walls are destroyed “merge” into larger air sacks that are physiologically ineffective. The capillaries of the alveolar walls are destroyed as well. When this happens, the elasticity of the lung is severely compromised. The consequence of that is reduced air flow in and out of the lung as well as impaired oxygen delivery and carbon dioxide clearance. The patient ends up with low oxygen (hypoxia) and high carbon dioxide (hypercapnia) in the blood.

And the consequences are…

Quite devastating. I am sure everybody is familiar with the wheelchair-bound person with emphysema who must inhale oxygen from an attached tank. The reason for this should be clear by now. In previous posts, we examined the role of oxygen in providing energy to the body’s cells.

Glucose is oxidized aerobically (with the help of oxygen) and provides energy in the form of ATP. When oxygen supply is limited, cells oxidize glucose anaerobically (without oxygen), a process that provides only a meager amount of ATP. This explains the lack of energy and limited exercise tolerance of people with emphysema. But wait, there is more!

The end product of anaerobic oxidation of glucose is lactic acid. Anybody who has done vigorous exercise knows the feeling of lactic acid accumulation in the muscles. Marathoners call it “hitting the wall”. Emphysema patients hit the wall after the slightest exertion. There are other complications that are out of the purview of this posting: low blood pH (acidosis) and heart failure, among others. But the root cause of all of them is low oxygen in the blood.


Who gets emphysema?

A lot of people—the numbers are truly alarming. The National Institutes of Health estimates that there are 12 million Americans with diagnosed emphysema and an additional 12 million who have it but haven’t yet been diagnosed.

Emphysema is now the fourth leading cause of death in the U.S. and is expected to be the third leading cause by the year 2020. As mentioned above, the leading cause of the disease, about 80% of cases, are due to tobacco smoking. The other 20% (which translates to about 2.4 million people) is made up of second-hand smoking, exposure to dust and air pollution, and a rare genetic deficiency disease (alpha 1 anti-protease deficiency).

One of the vivid pictures I still remember from my medical school days are the black lungs of two deceased people contained in a jar in the pathology lab. One lung belonged to a smoker; the other, to my great surprise, belonged to a non-smoker who lived in Los Angeles.

There is another chronic lung disease that is growing at an alarming rate due to air pollution: asthma, especially in children. The mechanism of this disease is different from emphysema, but the biochemical outcome is the same: impaired airflow to the lung, low oxygen delivery to the tissues. Are there any lingering doubts about the dangers of smoking? Or air pollution?


What is being done about it?

It is amazing to me that we know the ravages of tobacco and air pollution down to the molecular level—the science is irrefutable and beyond reproach. Yet, we had to fight the tobacco industry for many years to overcome their PR and the money they used to what amounts to bribery of our legislators. We continue to do less than is optimal to clean up air pollution. And, we still have a government that, rather than acknowledge science as a basis for public policy, uses the tactics similar to the tobacco and other vested industries to raise bogus doubts about the quality of the science and bullies scientists who simply report the facts.

Where is the outrage?