The Biology Of Emphysema - How Does Copd Develop: Respiratory Health

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The biology of emphysema

The underlying mechanism of emphysema is the destruction of the walls surrounding the alveoli, the tiny air sacs in the lungs. Normally, with every breath you take, air fills these millions of tiny sacs, and then oxygen slips through their thin walls into your bloodstream. At the same time, carbon dioxide, a waste product, passes from your bloodstream through the alveolar walls and into the air-filled sacs to be eliminated from your body when you exhale. The leading theory on the development of emphysema is that the process begins with an imbalance between certain types of proteases, enzymes that destroy the walls of the alveoli, and antiproteases, chemicals that keep the proteases in check (see Figure 3).

Figure 3: Close-up on emphysema Alveoli (air sacs) are intact and lined by blood-filled capillaries that absorb oxygen efficiently into the bloodstream. A proper balance of antiprotease keeps in check the elastase, which breaks down elastin in the walls. The walls of the alveoli are broken down, impeding air exchange. Destructive elastase attacks the elastin fibers, destroying the walls of the air sacs. The result is a lack of surface space and capillaries to deliver oxygen to the rest of the body.

Scientists who study emphysema have focused most of their attention on neutrophil elastase, a protease that breaks down lung tissue. Neutrophil elastase attacks elastin, a protein that forms a matrix of connective tissue in the alveolar walls. Under normal circumstances, antiproteases keep the proteases from degrading too much elastin, but when protease production is pumped up — because of chronic inflammation of the respiratory tract, for example — the antiproteases are far outnumbered. As a result, the neutrophil elastase attacks the elastin in your lungs, and the alveolar walls come toppling down. Fewer walls between air sacs result in larger but fewer sacs. And that's a problem because it means less surface area to absorb oxygen into the bloodstream.

To envision this, imagine that normal air sacs look like bunches of tiny grapes sprouting from stems in the lungs. But when damaged, the sacs become swollen and oddly shaped. Where once a cluster of tiny grapes nestled, a larger, misshapen balloon now exists with less total surface area filled with blood vessels that ferry oxygen into the blood and take carbon dioxide out of the blood. Each breath is less productive, so you have to work harder at breathing.

Smoking delivers a one-two punch. First, it increases the production of proteases that degrade elastin, and it may increase other proteases that attack the lungs as well. Second, it can interfere with the activity of protective antiproteases. Specifically, oxidants — destructive chemicals derived from cigarette smoke and inflammatory cells — appear to initiate a chemical chain of events that ultimately inhibits the activity of the major antiprotease in the lungs, called alpha-1-antitrypsin. Together, these assaults lead to the deformity of the air sacs.

As lung tissue breaks down, your lungs lose elastic recoil, the natural tendency to spring back into their resting position when you exhale. Elastic recoil is also helpful in pulling your airways open, allowing air to pass freely through them. When your lungs lose elastic recoil, two things happen. First, there is no longer that springing force that pushes air out when you exhale, so air gets trapped in the lungs. That makes it harder for you to exhale, and it also means you can't inhale as easily because the old air is taking up space in the lungs. Second, when the lungs lose elastic recoil, the airways leading to them narrow and tend to flop shut, adding to your difficulty inhaling and exhaling.

As you keep trying to breathe with air trapped in your lungs, your lungs become stretched too far (a condition called hyperinflation), like a balloon that's filled beyond capacity. The difference between lungs with emphysema and healthy lungs is like the difference between a tight new balloon and an old, stretched-out balloon. If you fill the two balloons with equal amounts of air and release the ends, the new balloon will expel the air much faster than the stretched-out balloon. Additionally, the overexpanded lungs push down on the diaphragm — a muscle between the chest and the abdomen that contracts with each inhalation — impairing its normal action. This also makes it harder for you to breathe and contributes to the sensation of shortness of breath.

By the time people begin to have symptoms of emphysema, they have usually lost 50% to 70% of their lung tissue. Even then, experiences vary. You may unconsciously breathe faster to compensate for the difficulty inhaling and exhaling. But if you can't compensate, the level of oxygen in your blood may get so low that it causes serious complications. One complication is pulmonary hypertension, elevated blood pressure in the pulmonary arteries, the vessels that carry blood from the heart to the lungs. Another complication is cor pulmonale, the enlargement and weakening of the right pumping chamber of the heart.

Last updated:	May 23, 2007