Pathology of Obstructive Pulmonary Diseases

Question 1

Define Pneumonitis? Pneumonia? Interstitial?

Answer 1

 “Pneumonitis” – inflammation located in the septal areas (septae, septum as synonyms)

 “Pneumonia” – general term meaning ‘infiltrative,’ non-neoplastic pathology anywhere in the lung

 “Interstitial/interstitium” – ‘supportive’ spaces, like septal, perivascular, and peribronchiolar

Question 2

Obstructive versus Restrictive:

Answer 2

As broad categories, obstructive and restrictive lung processes are ‘medical’ diseases (noninfectious, non-neoplastic, and often non-surgically treated), and have some overall differing features:

Obstructive - Increase in resistance to air flow anywhere from the trachea to the bronchioles
 FEV1/FVC < 0.7  Due to ideally distinct pathologies (see below)

Restrictive - Decreased total lung capacity from reduced expansion of the lung parenchyma
 FEV1/FVC usually normal, because all lung capabilities decrease  Occurs in one of two pathologic categories o Chest wall disorders (that usually limit expansion) o Interstitial and infiltrative diseases (that usually reduce lung plasticity)

Question 3

Explain the clinical entities of obstructive lung disease, their anatomic site, pathologic changes, etiology, and signs/symptoms?

Answer 3

Question 4

Explain Chronic Bronchitis?

Answer 4

Chronic) Bronchiolitis is sometimes referred to ‘small airway disease,’ and may be seen in any type of obstructive disease, and has a restrictive counterpart

Question 5

Obstructive diseases usually what?

Answer 5

This chart above implies these processes are independent and separate, but the reality of obstructive disease is that they are often overlapping (see below)

Question 6

Explain COPD?

Answer 6

COPD-Emphysema-chronic bronchitis

As an interrelated entity, these two conditions (which we’ll discuss separately) are known clinically as chronic obstructive pulmonary disease (COPD). Chronic bronchiolitis often complicates COPD as well.

 80% due to tobacco smoke (35-50% of heavy smokers develop COPD)

 Affects about 10% of population and is the 4th leading cause of death

 Risk factors include environmental/occupational exposures, and certain genetic polymorphisms

Question 7

Explain the diagnosis of chronic bronchitis? Emphysema?

Answer 7

Chronic bronchitis – clinical diagnosis
Chronic/recurrent cough and excess mucus production, starting first in the large airways

Emphysema – morphologic diagnosis
Affects the acinus level

Question 8

what is emphysema? what are the patterns?

Answer 8

Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, with destruction of their walls. Patterns include:

 Centriacinar - upper lobes, apical region, most common in tobacco smokers

 Panacinar - lower lung zones, a-1 antitrypsin deficiency (antiprotease)

 Distal acinar (paraseptal) - adjacent to pleura, lobular connective tissue septae, bullae formation, spontaneous pneumothorax in young adults

 Irregular acinar - acinus is irregularly affected and commonly seen in areas of scarring

Question 9

explain the images?

Answer 9

Images: (left) bullous emphysema;

(middle) centriacinar emphysema with arrows at expanding/microcystic bronchioles;
(right) diffusely expanded spaces representing altered alveoli in panacinar emphysema.

Question 10

pathophysiology of emphysema?

Answer 10

 Tobacco smoke produces reactive oxygen species leading to oxidative stress

 Inflammatory response causes a wide variety of cells and mediators to be attracted to the area, amplifying inflammation

 A protease-antiprotease imbalance can occur which promotes tissue breakdown:

o Neutrophils and macrophages produce elastase in response to tobacco, leading to the inactivation of antiproteases

o MMP’s from neutrophils and macrophages also contribute to tissue breakdown

Protease-antiprotease and oxidant-antioxidant imbalances cause self-perpetuating inflammation that persists even after smoking has ceased, leading to continued tissue destruction.

Question 11

Response to the damage in emphysema is controlled by?

Answer 11

Response to this damage is controlled by multiple genetic factors, thus there is marked individual susceptibility to development of (COPD) emphysema:
 TGF-β – with certain polymorphisms, mesenchymal cell response to TGF-β is reduced resulting in inadequate repair of elastin injury

 Matrix metalloproteinases polymorphisms can result in higher levels of MMP-9 and MMP-12, which are found increasingly in emphysema patients

Question 12

What does this show?

Answer 12

typical micro of emphysema with expanded/destroyed alveoli.

Question 13

What is chronic bronchitis? who gets this?

Answer 13

This is a clinical entity defined as persistent cough with sputum production for at least 3 months in at least 2 consecutive years.

 Cigarette smokers

 Long-term urban dwellers or those in smoggy cities

 20-25% of men aged 40-65

Chronic bronchitis overlaps and co-exists with emphysema, exacerbating decreased lung function.

Question 14

Pathogenesis of chronic bronchitis?

Answer 14

 Mucus hypersecretion in large airways as a protective response to inhaled, noxious agents

 General inflammation (as always) can be somewhat detrimental when long-term and in continued response to the noxious agent exposure

 Long-term chronic bronchitis can lead to atypical metaplasia and dysplasia

Question 15

Microscopic features of chronic bronchitis?

Answer 15

Microscopically, the characteristic feature would appear as mucus gland hyperplasia in the bronchi; bronchioles can also show mucus plugging and potentially fibrosis long-term.

Question 16

What is asthma? Hallmarks of asthma?

Answer 16

This immune-mediated cause of obstructive disease is a chronic inflammatory disorder of the conducting airways. Symptoms are typically episodic, and patients complain of cough, dyspnea, wheezing, and chest tightness. When asthmatic attacks last over several days (or even weeks), cyanosis and death can result (and is called status asthmaticus).

Hallmarks of asthma include:

 Intermittent & reversible airway obstruction

 Chronic bronchial inflammation with eosinophils

 Bronchial smooth muscle cell hypertrophy & hyperreactivity

 Increased mucus production

Question 17

What is the pathogenesis of asthma?

Answer 17

 Atopic etiology – IgE mediated, with evidence of an allergic sensitization (classic Type I hypersensitivity reaction

 Non-atopic etiology – May be due to respiratory viruses, inhaled air pollutants, or a drug reaction; pathogenesis is poorly understood

Triggers for both types are diverse and include infections, inhaled irritants, cold air, exercise, and gastroesophageal reflux disease (GERD), among many other causes, including genetic susceptibility.

Question 18

Gross and microscopic features of asthma?

Answer 18

Grossly, lungs appear hyperemic and overinflated, with the latter feature demonstrated by near touching of the lobes when the patient/body is lying prone; mucus and/or pus (if infection is present) can fill airways and form casts.
Microscopically, several features are seen:
 Mucus plugging with many eosinophils

 Increased in submucosal glands, with Goblet cell hyperplasia

 Hypertrophy/hyperplasia of smooth muscle

 Other airway remodeling, including thickened walls, sub-basement membrane fibrosis, increased vascularity

Question 19

what is this image depicting?

Answer 19

In sputum or bronchoalveolar lavage specimens, mucus plugs can be extruded from submucosal gland ducts or bronchi, and may take a shape called a Curshman spiral.

In asthma.

Question 20

What are these images showing?

Answer 20

Eosinophils are the typical inflammatory cell in asthma, both in mucus and in the tissue (see below left); an eosinophil protein called galactin-10 can aggregate and form Charcot-Leyden crystals (below right) in any medical condition with abundant eosinophils (not just asthma).

Question 21

What is Bronchiectasis?

Answer 21

This occurs when a chronic and often necrotizing infection causes permanent dilation of bronchi and bronchioles. Any condition that predisposes to airway obstruction increases the likelihood of bronchictasis occuring:

 Obstructive lung diseases (asthma, chronic bronchitis, emphysema), or other obstructions like tumors or foreign bodies

 Congenital and hereditary conditions (CF, Kartagener syndrome)

 Immunodeficiency states or autoimmune disorders leading to chronic infections

The pathogenesis is the eventual inflammatory-mediated destruction of smooth muscle and elastin that supports and surrounds the airways. This eventually leads to irregular dilation (see above image) of the airway and the potential for mucus plugging (see below image) and airway collapse. Notice in the bottom right of the image the cystic appearance characteristic of concomitant emphysema.