Pathophysiology of Emphysema

Jennifer Kong

Learning Objectives

At the end of this section, you will be able to:

  • Outline the physiological cause of emphysema as a disease of repeated injury, inflammation and remodelling.
  • Define the role of alpha-1-antitrypsin (AAT) in health and its role during the development of emphysema.
  • Identify key features of emphysema in lung tissue on a gross and histological level.
  • Explain how chronic inflammation and remodelling during emphysema leads to exhalation being an active process.


Emphysema is a  progressive respiratory disease whereby chronic injury and inflammation to the airways & alveoli result in their deformation and destruction.  The end result is a significant loss of gas exchange surface and  serious impairment of the lung’s natural elasticity needed for ventilation – particularly exhalation. Emphysema manifests in the mid- to later stages of life.

Causes of emphysema

For emphysema to develop, the lungs have had years worth of constant, repeated damage to the airways and alveoli, thus involving chronic inflammation and tissue remodeling.  Causes that are considered modifiable (i.e. there’s an opportunity to remove the recurrent injury) and non-modifiable (i.e.  can not avoid the recurrent injury).
Figure 5.13 Modifiable and Non-modifiable Causes of Emphysema
Modifiable causes Non-modifiable causes
Chronic inhalation of foreign particulate (eg.  air pollution, second hand smoke, working with fine dust or powders)  A rare, inheritable alpha-1-anti-trypsin deficiency
Chronic infection/inflammation of the lungs – especially in childhood
Recall that emphysema is one of the diseases lumped under the umbrella term COPD.  Thus, emphysema can concurrently occur with other COPD conditions like chronic bronchitis.

Pathophysiology of Emphysema

Regardless of the cause, emphysema is caused by repeated injury and inflammatory response in the lung tissue. As part of the inflammatory response, leukocytes – especially neutrophils – are recruited to the site of injury. Neutrophils release enzymes which degrade proteins in the irritant/pathogen.  Such enzymes (i.e.  proteases such as trypsin, elastase) can also degrade one’s own tissue’s proteins if it weren’t for the special protein alpha-1-antitrypsin (AAT) that deactivates any proteases approaching normal cells – akin to a  protective forcefield.  AAT is predominantly made in the liver, circulates continuously in the blood, and accumulates in lungs since lungs are exposed to pathogens (and hence, possible infection) with each breath.

But what happens if one frequently inhales harmful irritants?  The acute inflammatory process works as needed, but the lungs run out of AAT. Rather, AAT is consumed by the frequent inflammatory response, faster than the liver can make it and circulate. As a result, the proteases released by neutrophils during inflammation will go uninhibited:  digesting the proteins in both the irritant/pathogen AND the lungs.  As a result, the lungs get damaged by its own cells – causing more of an inflammatory response and so forth.  The result:  loss of lung tissue and remodeling of airways to a non-elastic tissue (since proteases repeatedly digest the lung’s natural elastin).  The loss of lung tissue particularly alveolar walls – is noticed microscopically and by gross inspection in that the fine holes/bubbles in lung tissue are larger, distorted blebs as airspaces from digested alveoli coalesce to form a single larger air space.  Similarly, alveoli & airways – particularly bronchioles – are remodeled due to chronic inflammation, becoming inelastic.  This is particularly noticeable in the airways as the airways have narrowed and lost its ability to stay open during exhalation (i.e. airways collapse). At the same time,  alveoli, with their larger than normal airspace, can’t recoil to a smaller volume during exhalation due to their remodeled inelastic nature.  The end effect is that air is “trapped” inside lungs because the elastic-driving force of exhalation has been lost to remodeling.


a flow chart of the pathogenesis of emphysema
Figure 5.14 – Pathophysiology of Emphysema by Jennifer Kong. Created under a CC-BY-NC license

Gross pathology of emphysema

For a stark contrast in the effects of emphysema, compare the normal lung to the emphysema specimen – suspended in formalin.

Figure 5.8 DHPLC specimen: A000Normal Lung Tissue With Blood Washed Out. All rights reserved


Note the striking difference in colour:  the emphysema lung is black with the cigarette tar of frequent tobacco use.  The emphysema lungs have ‘shaggy’ tissue with large holes – one hole is so large that is perforates through the entire specimen (top left). Notice that bronchioles in normal lung are numerous and can be easily identified whereas the emphysema specimen airways are smaller in number and not as  discretely identifiable.

Key Features of Emphysema at Gross Level by Jennifer Kong, licensed under  All rights reserved


To visualize the smaller and finer bronchioles, we now present Gough sections of normal and emphysema lung, both photographed at the level of the  naked eye.


Figure 5.16 Normal lung  (Gough section). All rights reserved

The emphysema specimen gives the impression of a decaying leaf – which is a good comparison considering the amount of lung tissue lost during years of chronic injury and inflammation. The emphysema lung has obvious signs of large air spaces, a result of alveolar wall destruction and coalescing of air spaces. Much of the lung tissue has become very thick with the impression of being stiff.  Like the previous specimens, the emphysema lung retains much of the black residue from cigarette usage.

Histopathology of Emphysema

Critical thinking Exercise

Before viewing histopathologist Jon’s video, consider what you already know about emphysema and what you would expect to see histologically. Privately record your answers to these questions before viewing the video

  • In the histology chapter, you learned there are certain epithelial types you see within lung tissue. Which cell type would form the alveolar wall?  the airways?
  • What do you expect to see with respects to alveolar size, knowing there is destruction & remodeling?
  • What do you think those enlarged airspaces, easily visible with the naked eye, will look like microscopically?
  • What do you think the overall pattern of the emphysema tissue sample be?  Will it be a predictable, homogeneous pattern?
  • What do you think cigarette residue within lung tissue will look like microscopically?
  • How would you observe the remodeling of lung tissue into inelastic connective tissue?

Histopathology of Emphysema by Jonathan Bush.  All rights reserved

Section Review

  • Due to chronic injury and/or insufficiency of alpha-1-antitrypsin in the lung, the inflammatory process destroys both the inhaled irritant AND normal healthy lung tissue.  As a result, there is loss of lung tissue – particularly evident in alveolar walls – and remodeling of lung tissue to  thicker, stiffer, less compliant properties.
  • Because the lungs have lost their elasticity through remodeling, airways are narrowed and collapsible – especially during exhalation – resulting in an incomplete exhalation of the normal expiratory volume. The end result is some air being ‘trapped’ in the alveoli and thus lungs with each breath.
  • Exhalation becomes progressively more difficult as the elastic recoil of healthy lung tissue is lost and the airways become narrowed and more likely to collapse.  As a result, exhalation changes from a passive process to an active effort.
  • Repeated inflammation causes loss of alveolar tissue. Thus causing expansion of alveolar air spaces with less area for gas exchange.  These coalesced air spaces are visible histologically.
  • Emphysema lung tissue may retain some of the inhaled irritants, thus changing the colour of lung tissue.

Review Questions



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Pathology Copyright © 2022 by Jennifer Kong is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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