The buildup of extravascular fluid in the lungs is called pulmonary edema. Pulmonary edema is a common complication of cardiac and noncardiac disorders. Cardiogenic pulmonary edema results from left heart failure, valvular heart disease, and obstruction in the left chambers of the heart (pulmonary edema can be the first sign of coronary heart disease). Noncardiogenic causes include fluid overload, renal failure, acute respiratory distress syndrome, drug reactions, narcotics (heroin), toxic inhalation, and near drowning. The actual mechanism may be due to increased hydrostatic pressure in the capillaries and venules and/or changes in vessel permeability. Pulmonary edema can be a chronic condition, or it can develop suddenly and quickly become life threatening. The life-threatening type of pulmonary edema occurs when a large amount of fluid suddenly shifts from the pulmonary blood vessels into the interstitium and/or alveoli.

The sequence of events for the development of pulmonary edema is always the same, regardless of the etiology. It consists of an early interstitial phase, where fluid accumulates in the alveolar interstitium, and a second stage, where fluid is present in the alveoli. The pathologist depends on the staining of protein within the edema fluid to make a histologic diagnosis of edema. If there is edema fluid with a minimal amount of protein, it may be difficult to make the diagnosis of pulmonary edema even when clinical, radiologic, and physiologic methods detect the presence of edema in the patient. The protein that accompanies edema fluid is seen as intra-alveolar eosinophilic material filling the airspaces. Other conditions in which eosinophilic material occupies alveoli are pulmonary alveolar proteinosis and Pneumocystis carinii pneumonia. Pulmonary edema lacks the granularity, coarse granules, cholesterol clefts, and macrophages of alveolar proteinosis. Pneumocystis pneumonia also shows intra-alveolar eosinophilic material, but the intra-alveolar material displays a foamy appearance that corresponds to the cysts.