Macroscopically atelectasis is characterized by a dark blue-red color of the lung. On the surface, the atelectatic areas are beneath adjacent lung areas with normal air content. In resorption atelectasis, the border of the atelectatic areas is sharp following the lobular borders, whereas in compression atelectasis, the border is blurred.

Histologically the alveoli are collapsed, and the capillaries are usually prominent, filled with blood. Cave: collapsed alveoli can only be seen, when the lung tissue is properly fixed (see Chap. 23).

The consequences of atelectasis are largely dependent on the size of atelectasis: small foci might not cause symptoms at all. Larger atelectatic areas will cause impaired blood flow and congestion. Long-standing atelectasis is also prone to secondary infection. If the area is large involving a whole lobe or more, also hypertension can result.

Macroscopically emphysema can be diagnosed if the enlarged alveoli can be seen with the naked eye – this is the main and most reliable criterion (Fig. 5.4); normal alveoli are just below the size a human eye can recognize, so they are invisible. Another but less reliable sign is protrusion of the emphysematous segments over adjacent ones. In old German pathology books, there is always a description of depigmentation and of “knistern” (crackles) when pressing the lung: both are not signs of emphysema. As the lung is an organ filled with air, any kind of pressure will cause the air to bypass into other segments/saccules. By applying pressure, channels of Lambert and pores of Kohn are opened and cause these crackles. A normal lung has a rosy-red color. Deposition of pigments from the ambient air causes pigmentation of the lungs over the years. In case of emphysema, there is some depigmentation; however, again this is not a reliable sign of emphysema.

On histologic examination, a proper fixation is required; otherwise, only high grades of emphysema can be diagnosed. Emphysema can be diagnosed, if there is increased size of alveoli with any kind of remodeling of the architecture of the lung. Linear intercept can be used for the diagnosis: a line is drawn between two adjacent bronchioles, which should cross at least seven alveolar walls. Everything below this value can be attributed to emphysema. Emphysema grading can be done according to the work of W. Thurlbeck into grades 1–9 [8]. It can easily be done without morphometry; even the most significant morphometric parameter, linear intercept, can be included. The classification has a good correlation with lung function and HRCT (see below). However, still a lot of correlation studies have to be done.

Emphysema can be classified into:

There are other classifications, such as by size into vesicular and bullous emphysema or by the underlying cause, i.e., obstructive emphysema. None has gained a significant acceptance.

Panlobular (panacinar) emphysema is caused by an inherited α1-antitrypsin deficiency. Usually mutations are located on exons 2–5 of the α1-antitrypsin gene, located on chromosome 14 (SERPINA1). There are different degrees of deficiency, depending on the type of mutation [9]. The most severe form is caused by missense mutations resulting in a truncated nonfunctioning protein. Other mutations, usually base exchange, will result in a change of the amino acid composition of α1-antitrypsin. If the amino-terminal portion of the protein is affected, this causes a biologically less efficient protein. α1-antitrypsin is responsible in counteracting the action of inflammatory proteins/peptides and is thus responsible for maintaining the structure of the lung. Each time a toxic substance is inhaled, an inflammatory response is started, but the action of the inflammation is terminated by α1-antitrypsin and some other anti-inflammatory molecules. Thus, the way for regeneration is paved.

Panlobular emphysema development starts in alveoli, affecting peripheral portions of the primary lobule, but leaving bronchioles and alveolar ducts unaffected. There is no visible inflammatory reaction/infiltration. In later stages, more and more lobules are involved, and also central portions with their alveolar ducts and respiratory bronchioles are included in cyst formation and enlargement. At the final stage, such as in explanted lung at transplantation, it might be almost impossible to separate panlobular from centrilobular emphysema (Figs. 5.5, 5.6, and 5.7).

An enlargement of the bronchioloalveolar unit characterizes centrilobular (centriacinar) emphysema: terminal bronchioles, alveolar ducts, and the centrally located alveoli are widened. Inflammation is often present, especially chronic bronchiolitis. In later stages, the more peripherally located alveoli are also included into the emphysema, and this results in the formation of large vesiculae or bullae. The alveolar septa usually rupture, and remnants can easily be seen (Figs. 5.8 and 5.9) [10]. As a consequence of chronic bronchiolitis, fibrosis of the bronchial and bronchiolar walls can be seen.

In cases of chronic bronchitis and bronchiolitis combined with centrilobular emphysema, the diagnosis of chronic obstructive pulmonary disease (COPD) can be rendered also pathologically. Centrilobular emphysema is most often associated and caused by cigarette smoking. The mechanism is not entirely understood, but there are some data pointing that cigarette smoking shifts the balance of pro-inflammatory and anti-inflammatory proteins toward the pro-inflammatory side, and thus lung tissue is destroyed gradually. Several other factors may interplay, such as defects of degradation-associated enzymes in alveolar macrophages and also phenotypic variation in the expression of different metalloproteinases [11–13]. Recent investigations have shed light on the role of immune mechanisms in emphysema development (detailed discussion below).