To understand ARDS, it is important to review how the lungs work. Air, which contains oxygen, is inhaled through the nose and mouth, and passes into the windpipe (trachea). From the trachea, air flows through tubes called bronchi into microscopic air sacs called alveoli. Very small blood vessels (capillaries) are imbedded in the walls of these air sacs. Oxygen passes through the thin walls of the alveoli into the bloodstream. Carbon dioxide, a waste product of cellular function throughout the body, passes from the bloodstream into the alveoli and then is exhaled. At the onset of ARDS, lung injury may first appear in one lung, but then quickly spreads to affect most of both lungs.

When alveoli are damaged, some collapse and lose their ability to receive oxygen. With some alveoli collapsed and others filled by fluid, it becomes difficult for the lungs to absorb oxygen and get rid of carbon dioxide. Within one or two days, progressive interference with gas exchange can bring about respiratory failure requiring mechanical ventilation.

As the injury continues over the next several days, the lungs, fill with inflammatory cells derived from circulating blood and with regenerating lung tissue. Fibrosis (formation of scar tissue) begins after about 10 days and cam become quite extensive by the third week after onset of injury. Excessive fibrosis further interferes with the exchange of oxygen and carbon dioxide. The sequential stages of ARDS are described in further detail below.