Emphysema

  • Generally lung diseases are of obstructive and restrictive.
  • Obstructive lung diseases or airway diseases are characterized by an increase in resistance to airflow due to partial or complete obstruction at any level from the trachea and larger bronchi to the terminal and respiratory bronchioles.
  • Restrictive diseases are those which are characterized by reduced expansion of lung parenchyma and decreased total lung capacity.
  • Common obstructive lung diseases include emphysema, chronic bronchitis, asthma and bronchiectasis.
  • Emphysema and chronic bronchitis are often clinically grouped together and referred to as chronic obstructive pulmonary disease (COPD)
  • Since the majority of patients have features of both, almost certainly because they share a major trigger-cigarette smoking.

 

Emphysema:

  • Emphysema is characterized by irreversible enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls without obvious fibrosis.
  • Emphysema is classified according to its anatomical distribution within the lobule.
  • Lobule is a cluster of acini, the terminal respiratory units.
  • Based on the segments of respiratory units that are involved, emphysema is classified into four major types
  1. Centriacinar
  2. Panacinar
  3. Paraseptal
  4. Irregular

 

  • Of these , only the first two cause clinically significant airflow obstruction.
  • Centriacinar emphysema is the most common form, constituting more than 95% of clinically significant cases.

Centriacinar (centrilobular) emphysema:

  • In this type of emphysema the central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared.
  • Thus ,both emphysematous and normal airspaces exist within the same acinus and lobule.
  • These lesions are more common and usually more severe in the upper lobes, particularly in the apical segments.
  • Inflammation around bronchi and bronchioles is common
  • In severe centriacinar emphysema, the distal acinus may also be involved , making differentiation from panacinar emphysema difficult.
  • Centriacinar emphysema occurs predominantly in heavy smokers ,often in association with chronic bronchitis (COPD)

 

Panacinar (panlobular) emphysema:

  • In this type,the acini are uniformly enlarged from the level of respiratory bronchiole to the terminal blind alveoli.
  • The prefix pan refers to the entire acinus , not the entire lung.
  • In contrast to centriacinar emphysema, panacinar emphysema tends to occur more commonly in the lower zones and in the anterior margins of the lung , and it is usually most severe at the bases.
  • This type of emphysema is associated with alpha1-antitrypsin deficiency.

 

Distal acinar (paraseptal) emphysema:

  • In this type,the proximal portion of the acinus is normal, and the distal part is predominantly involved.

 

 

Irregular emphysema:

  • It is named so because the acinus is irregularly involved, and is involved with scarring.
  • It is airspace enlargement with fibrosis.
  • It is clinically insignificant.

Pathogenesis:

  • Inhaled cigarette smoke and other noxious particles cause lung damage and inflammation, which results in parenchymal destruction (emphysema) and airway disease (bronchiolitis and chronic bronchitis).

 

  • Factors that influence the development of emphysema include

 

  • Inflammatory mediators and leucocytes:
  1. Inflammatory mediators like leukotriene B4 ,IL-8 ,TNF and others have been increased in the affected parts.
  2. These mediators are released by resident epithelial cells and macrophages, and attract inflammatory cells from the circulation(chemotactic factors), amplify the inflammatory processes and induce structural changes.

 

  • Protease-antiprotease imbalance:
  1. Several proteases are released from the inflammatory cells and epithelial cells that break down connective tissue components.
  2. In patients who develop emphysema, there is relative deficiency of protective antiproteases, which in some cases may be genetic bases

 

  • Oxidative stress:
  1. Substances in tobacco smoke, alveolar damage,and inflammatory cells all produce oxidants, which may beget more tissue damage and inflammation.
  2. Here NRF2 gene is inactivated
  3. NRF2 encodes a transcription factor that serves as a sensor for oxidants in alveolar epithelial cells and many other cell types.
  4. Intracellular oxidants activate NRF2 , which upregulates the expression of multiple genes that protect cells from oxidant damage.

 

  • Infection:
  1. It may not be the initiator for tissue destruction but it exacerbate the associated inflammation and chronic bronchitis.

 

Clinical course:

  • Symptoms do not appear until atleast one third of the functioning pulmonary parenchyma is damaged.
  • Dyspnea usually appears first, beginning insidiously but progressing steadily.
  • Cough or wheezing is the chief complaint.
  • Cough and expectoration are extremely variable.
  • Weight loss
  • Barrel shaped chest
  • Impaired expiratory airflow
  • Patients may overventilate and remain well oxygenated and are designated as pink puffers.

Morphology:

  • Advanced emphysema produces voluminous lungs, often overlapping the heart and hiding it when the anterior chest wall is removed.
  • Generally, upper two thirds of the lungs are more severely affected.
  • Large apical blebs or bullae are more characteristic of irregular emphysema secondary to scarring and of distal acinar emphysema
  • Microscopically, abnormally large alveoli are separated by thin septa with only focal centriacinar fibrosis.

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