Lung
Obstructive pulmonary disease
Emphysema
Topic Completed: 1 December 2016
Minor changes: 20 July 2020
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: emphysema[title]
Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Radiology description | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Electron microscopy images | Videos | Differential diagnosis | Additional referencesCite this page: Yoshikawa A, Bychkov A. Emphysema. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungnontumoremphysema.html. Accessed January 24th, 2021.
Definition / general
- Pulmonary emphysema is defined as permanent abnormal enlargement of air spaces distal to the terminal bronchioles with destruction of the alveolar septa with little or no fibrosis
- In a broad sense, emphysema refers to the condition when air is abnormally introduced and trapped in the tissue; it can occur in any part of body such as subcutaneous soft tissue, mediastinum, epidural area and solid organs
Essential features
- Destruction of acinar structure and airspace enlargement, especially due to cigarette smoking
- Affects multiple pulmonary functions and causes chronic respiratory symptoms
Terminology
- Major types (Lancet 2004;364:709, Int J Chron Obstruct Pulmon Dis 2008;3:193):
- Centriacinar, centrilobular or proximal acinar emphysema (most associated with smoking and COPD)
- Panacinar or panlobular emphysema
- Paraseptal or distal acinar emphysema
- Minor types
- Combined pulmonary fibrosis and emphysema (CPFE)
- Interstitial emphysema
- Bullous emphysema
- Senile emphysema
- Irregular emphysema
- Congenital lobar emphysema
Epidemiology
- COPD is the third leading cause of global death (Lancet 2012;380:2095)
- Affects 1.4% of adults in the US (CDC, American Lung Associiation)
- Male : Female = 1 : 0.9
- Usually older than 45 years old
Sites
- Centriacinar emphysema
- Upper lobe predominant
- Respiratory bronchioles and surrounding lung parenchyma
- Panacinar emphysema
- Lower lobe predominant
- Entire acinus
- Paraseptal emphysema
- Upper lung
- Distal part of acinus in subpleural area
Pathophysiology
- Destruction of lung parenchymal tissue due to chronic inflammation
- Protease mediated destruction of elastin is an important feature (Thorax 2016;71:105)
- Morphological progression (Int J Chron Obstruct Pulmon Dis 2016;11:2287, Clin Anat 2015;28:227)
- Increase in size and number of small fenestrae in alveolar walls ("pores of Kohn"), which leads to loss of elastic recoil
- Breakdown and merging of fibrovascular trabeculae ("framework")
- Remodeling of acini results in airspace enlargement
Etiology
- Inhalation
- Cigarette smoking and environmental pollutants, especially for centriacinar emphysema
- However, there is individual susceptibility (Annu Rev Physiol 2014;76:493)
- Infections
- Genetic factors
- Alpha-1-antitrypsin deficiency is well known risk factor, especially for panacinar emphysema (Eur Respir J 2016 Oct 20 [Epub ahead of print], Lancet 2004;364:709)
- Telomerase mutations, especially for CPFE (J Clin Invest 2015;125:563)
- Serpin mutation (BMC Med Genet 2010;11:159)
Clinical features
- Dyspnea; chronic, progressive and usually irreversible
- Chest inflation
- CPFE (Chest 2012;141:222, Eur Respir J 2005;26:586)
- Coexistence of interstitial fibrosis and emphysema of unknown causes
- Patients with CPFE have different pulmonary function tests and outcomes than patients with pure emphysema or pure fibrosis
- Interstitial emphysema (Am J Surg Pathol 2014;38:339)
- Air gains access to the pulmonary interstitium to cause air leak and pneumothorax
- Common in premature infants
- Adults: commonly in usual interstitial pneumonia, but can occur in any interstitial lung diseases
- Bullous emphysema
- Formation of multiple bullae > 1 cm with thin wall
- Can cause bullae inflation and pneumothorax
- Senile emphysema
- Due to age related alteration of acini
- Irregular emphysema
- Occurs in relation to scars
- Congenital lobar emphysema (Pediatr Clin North Am 1994;41:453)
- Hyperinflation of one or more lobes due to malformation of bronchioles
- Causes respiratory distress
- Can be sporadic or caused by autosomal dominant inheritance
Radiology description
- X ray: overinflation of the lung, but it may not be seen in early stages
- Chest CT: emphysematous regions are represented by low attenuation areas (Eur Respir J 2016;48:216)
Prognostic factors
- Based on exacerbation risk of COPD (GOLD)
- GOLD score 3 or 4 (severe or very severe airflow limitation)
- Previous history of exacerbation and hospitalization
- Faster loss of forced expiratory volume in 1 sec
- COPD assessment test score ≥ 10 (CATest, Eur Respir J 2009;34:648)
Case reports
- 18 day old infant with interstitial emphysema (BMC Pulm Med 2016;16:139)
- 31 year old woman with congenital lobar emphysema (Surg Today 2013;43:539)
- 32 year old woman with severe bullous emphysema (Asian Cardiovasc Thorac Ann 2016;24:597)
- 34 year old man and his baby with congenital lobar emphysema (J Pediatr Surg 2002;37:799)
- 65 year old woman with severe emphysema (Clin Respir J 2015 Dec 24 [Epub ahead of print])
- 83 year old man died of CPFE (Int J Chron Obstruct Pulmon Dis 2015;10:1299)
Treatment
- Based on treatment of COPD (GOLD)
- Smoking cessation
- Medications: bronchodilators, antimuscarinic drugs, steroids, etc.
- Ventilatory support
- Surgical interventions: lung volume reduction surgery, bullectomy, lung transplant
- Augmentation therapy for alpha-1-antitrypsin deficiency (Eur Respir Rev 2015;24:46)
Clinical images
Images hosted on other servers:
Case of alpha-1-antitrypsin deficiency
Centriacinar emphysema
Panacinar emphysema
Paraseptal emphysema
CPFE
Gross description
- Centriacinar: sparse empty spaces with pigmentation (anthracosis) corresponding enlarged airspaces
- Panacinar: airspaces are more or less evenly inflated throughout the secondary lobules
- Paraseptal: inflated subpleural airspaces with thin walls
Gross images
Images hosted on other servers:
Centriacinar emphysema
Panacinar emphysema
Paraseptal (distal acinar) emphysema
Lung with cystic spaces due to destruction of airsac walls
Dilated airspaces with emphysema
Large bullae on surface of lungs
Centrilobular
emphysema with
focally appearing
holes
Microscopic (histologic) description
- General findings
- Airspace enlargement; the size of airspace in the background parenchyma will be a good reference
- Fragmented alveolar walls
- If the acinar arrangement is well remained, it is representing pores of Kohn
- If not, it is representing acinar destruction
- Mild fibrotic change can be seen
- Any degrees of inflammation can accompany
- The subtype is determined with histological landmarks:
- Bronchovascular bundle of terminal bronchiole and arteriole is in the center of acinus
- Connective tissue septa ("secondary lobule of Millar") are the periphery of acinus, which is often ambiguous in less inflamed lung
- Note: similar appearance can be seen due to inadequate inflation or fixation of specimen
- CPFE
- Centrilobular emphysema in upper lobes
- Usual interstitial pneumonia in lower lobes
- Interstitial emphysema
- Elongated or angulated spaces in fibrotic interstitium
- Surrounded by dense fibrosis and lining of multiple giant cells, but not epithelium
- Most commonly around bronchovascular bundles
Microscopic (histologic) images
Contributed by Akira Yoshikawa, M.D.
Nonemphysematous lung; right: peribronchiolar region
Centriacinar emphysema; right: with focal fibrotic change
Panacinar emphysema
Paraseptal emphysema with focal fibrotic change
Interstitial emphysema; right: honeycomb is also seen
Images hosted on other servers:
Subtypes of pulmonary emphysema
Progression model of pulmonary emphysema
Centriacinar emphysema
Virtual slides
Images hosted on other servers:
Severe emphysema
Electron microscopy images
Images hosted on other servers:
Remodeling of elastin and collagen
Videos
Histopathology Lung - Emphysema
Differential diagnosis
- Interstitial emphysema vs. honeycomb of usual interstitial pneumonia: honeycomb is the air space surrounded by bronchiolar epithelium on fibrotic wall
- Lymphangiomyomatosis: cystic air spaces, proliferation of spindle to epithelioid cells (HMB45+)
- Pulmonary Langerhans cell histiocytosis: stellate nodules with fibrosis and Langerhans cells (CD1a+)
