Emphysema

EMPHYSEMA

• Chronic obstructive pulmonary disease –

  Group of pathological conditions with chronic, partial / complete, obstruction of the airflow at any level from trachea to the smallest air ways resulting in functional disability of the lungs

• Entities included under COPD are

  • Chronic bronchitis

  • Emphysema

  • Bronchial asthma

  • Bronchiectasis

  • Bronchiolitis

EMPHYSEMA

• Definition – Abnormal permanent dilatation of air spaces distal to the terminal bronchioles along with destruction of the walls of dilated air spaces without obvious fibrosis

PATHOGENESIS OF EMPHYSEMA

• Etiologic factors

  • Tobacco smoke & Air Pollutants

  • Occupational exposure

  • Infections

  • Familial and  Genetic

• Initiating factor – chronic irritation by inhaled substances tobacco smoke, cotton and silica dust

• Bacterial and viral infections exacerbate the disease

• Factors influencing the development of emphysema are –

  • Inflammatory mediators and leukocytes – attract more inflammatory cells causing tissue damage

  • Protease and Antiprotease imbalance – protease released from inflammatory cells and damaged epithelial cells cause tissue destruction

  • Oxidative stress – substance in tobacco smoke, damaged alveolar cells and inflammatory cells produce oxidants which cause more tissue damage

  • Infection – exacerbates the associated inflammation

• Inflammatory mediators and leukocytes

  • Inhaled cigarette smoke and other irritants cause lung damage and inflammation

  • Inflammatory cells like macrophages, CD8+T cells and neutrophils infiltrate lung tissue and release variety of mediators like Leukotriene B4, IL-8, TNF and other mediators which damage lung structures or sustain neutrophilic infiltration

  • Neutrophils release elastases and proteases which damage the lung tissue

• Protease – antiprotease hypothesis

  • Genetic deficiency of antiprotease α1 antitrypsin have enhanced tendency to develop pulmonary emphysema

  • Alpha -1 antitrypsin (α1 protease inhibitor) is a α1-globulin protein encoded by the proteinase inhibitor locus on chromosome 14. Normal phenotype is PiMM.

  • Synthesized in liver and is distributed in circulating blood, tissue fluids and macrophages

  • Alpha -1 antitrypsin inhibits proteases particularly elastase secreted by neutrophils during inflammation

  • Abnormal phenotype is PiZZ – inhibits the release of Alpha -1 antitrypsin from liver.

 

• Deleterious effect of smoking

  • Neutrophils and macrophages accumulate in alveoli possibly due to chemoattractant effects of nicotine and ROS present in smoke

  • Neutrophils are activated and release their granules rich in elastase, proteinase 3 and Cathepsin G which causes tissue damage

  • Smoking activates macrophages which release elastase and metalloproteinases causing tissue damage

 

MORPHOLOGY

• • Gross :

    • Lungs – Voluminous, pale with little blood

    • Mild cases – Dilatation of airspace   

    • Advanced – Subpleural bullae and  blebs  

    • Bullae – Air filled cystic structures  > 1 cm 

    • Blebs – Rupture of alveoli directly into subpleural interstitial tissue

  • Depending upon the anatomic distribution within lobule emphysema is classified into

    • Centriacinar (Centrilobular)

    • Panacinar (Panlobular)

    • Paraseptal (Distal acinar)

    • Irregular          (Para – Cicatrical)

    • Mixed (Unclassified)   

  • CENTRIACINAR EMPHYSEMA

    • Involvement of central or proximal part of the acinus where as distal part is spared

    • Usually co-exists with chronic bronchitis

    • Predominant in smokers /  coalminers pneumoconiosis

    • Morphology-

      • Gross : Common in upper lobes of lungs

      • C/S : Distended air spaces in centre of lobules surrounded by a rim of normal lung parenchyma

    • Microscopy :

      • Distension & destruction of respiratory bronchiole & narrowing of terminal bronchiole

  • PANACINAR EMPHYSEMA

    • All portions of the acinus are affected

    • Often associated with α1-AT  deficiency in  smokers

    • Gross :

      • Common in lower zone of lungs

      • Enlarged & over inflated lungs

    • Microscopic examination :

      • All portions of acini are distended with thin & stretched alveolar walls

      • Spurs of broken septa due to rupture of  alveolar walls

    • Special stains :  Loss of elastic tissue

  • PARASEPTAL (DISTAL) EMPHYSEMA

    • Involves only distal part of acinus whereas proximal part is normal

    • Localised along the pleura & perilobular septa

    • More severe in the upper half of the lungs

    • Common cause of spontaneous pneumothorax in young adults

  • IRREGULAR (PARA-CICATRICAL) EMPHYSEMA

    • Seen surrounding scars from any cause

    • Irregular involvement

    • Usually asymptomatic

    • May be incidental autopsy  finding

  • MIXED EMPHYSEMA

    • Usually occurs in severe cases

    • Mixture of Centriacinar in upper lobes, Panacinar in lower lobes & Paraseptal in subpleural region

COMPLICATIONS OF EMPHYSEMA

• • Respiratory failure

  • Right heart failure

  • Coronary artery disease

  • Massive collapse of the lungs secondary to pneumothorax

Reference 

1. Vinay kumar, Abul K.Abbas, Nelson Fausto, Jon C. Aster. Robbins and Cotran Pathologic basis of disease. 8th edition.