0902 - Pathophysiology of Restrictive Lung Disease and Fibrosis

Question 1

What Cells would you find in the alveoli?

Answer 1

Type 1 pneumocytes (40%) - Simple squamous - gas exchange
Type 2 pneumocytes (60%) - Cuboidal - surfactant
In bronchioles - also find Club (Clara) Cells - secrete mucus.

Question 2

What pulmonary factors can affect gas exchange?

Answer 2

Quality of gas inhaled (FiO2)
Expansibility of the lungs (ribs, muscles, pleura, lung parenchyma)
Exchange of gases (basement membranes, interstitial thickness, alveolar deposits)
Perfusion

Question 3

What is a diffuse pulmonary disease?

Answer 3

Involve the entire lung and usually cause dyspnoea. Generally classified as obstructive (airway obstruction) or restrictive (restricted expansion of lung parenchyma).

Question 4

Outline some ways in which lung diseases can be classified:

Answer 4

Functional (Restrictive vs Obstructive)
Clinical (Acute vs Subacute vs Chronic)
Aetiology (Idiopathic, Asbestosis)
HRCT findings (based on patterns)
Pathologic reaction pattern (fibrotic, granular)
Site of injury (pleural, vascular, bronchiolar)

Question 5

Looking at spirometry, what is a quick way to tell between obstructive and restrictive lung diseases?

Answer 5

Obstructive - increases most things, particularly FRC, but decreases FEV1/FVC.
Restrictive - Decreases most things, particularly IRV and TV, but not FEV1/FVC.

Question 6

What are the possible causes of restrictive lung disease?

Answer 6

Disorders of Chest wall (lungs normal) - e.g. neuromuscular or obesity
Disorders of the Pleura
Disorders of the lung:
- Acute (diffuse alveolar damage)
- Chronic - fibrosis, granlomatous inflammation, smoking-related etc.

Question 7

What is the pathogenesis of acute restrictive pulmonary disease (acute respiratory distress syndrome)?

Answer 7

Capillary endothelial or alveolar damage usually secondary to infection, shock, or aspiration of vomit.
Inflammatory response (cytokines, interleukins, neutrophils, increased vascular permeability); leads to
Thickened alveolar walls (hyaline forming), alveolar flooding and decreased diffusion.

Question 8

What are the characteristics of acute restrictive pulmonary disease (acute respiratory distress syndrome)?

Answer 8

Diffuse alveolar damage
Diffuse alveolar capillary damage
Shock
Severe cyanosis and arterial hypoxemia
It is refractory to O2 therapy and often leads to respiratory acidosis and death.

Question 9

What are the histological characteristics of acute restrictive pulmonary disease (acute respiratory distress syndrome)?

Answer 9

Macroscopic - Heavy, ‘boggy’, oedematous, red lungs

Microscopic - air spaces still exist, but significant widening of interstitium and hyaline membranes around alveoli.

Question 10

What are the characteristics of chronic restrictive pulmonary diseases?

Answer 10

Very heterogenous, many idiopathic, and smoking plays a role.
Most commonly environmental (25%), Granulomatous (sarcoidosis 20%), idiopathic (10%) or collagen vascular).
Characterised by diffuse and chronic involement of pulmonary connective tissue (interstitium). Interstitial lung diseases.
History and radiology are very important for a diagnosis.
Prognosis is very varied, but generally poorer with increased fibrosis.

Question 11

How can you tell fresh fibrosis from old?

Answer 11

Fresh has lots of ECM without much collagen - lots of fibroblasts.
Old has lots of collagen, not many fibroblasts or cells at all in affected area.

Question 12

What are the clinical signs of chronic restrictive pulmonary diseases?

Answer 12

Dyspnoea (different onsets, can come and go)
Tachypnea
Inspiratory crackles
Reduced lung compliance and volume.

Question 13

What are the radiologic signs of chronic restrictive pulmonary diseases?

Answer 13

Irregular lines
Small nodules
Ground Glass shadows.
Distribution very important (diffuse or lobular?)

Question 14

What is the common pathogenesis of chronic restrictive pulmonary diseases?

Answer 14

Different mechanisms lead to inflammation of alveoli
Inflammatory response leads to accummulation of inflammatory cells in alveolar walls, and release of mediators (cytokines and interleukins). These damage the alveolar walls
Fibrosis of the alveolar walls - this is irreversible and carries a poor prognosis.

Question 15

What are the pneumoconioses?

Answer 15

Umbrella term for lungs reaction to inhalation of dusts, fumes and vapours - includes silicosis, asbestosis etc.

Question 16

What are the complications of chronic restrictive lung diseases?

Answer 16

End-stage honeycomb lung - lung is destroyed and scar tissue prevalent.
Traction bronchiectasis - scar tissue contracts, pulling bronchi open
Pulmonary hypertension secondary to the lung disease
Right sided heart failure (Cor pulmonale)

Question 17

What factors affect the progression of lung disease?

Answer 17

Duration and length of exposure
Amount of retained dust
Size (small particles can reach and settle in distal alveoli)
Shape and boyancy of particles
Solubility of particles
Additional irritants (SMOKING)
Pre-existing lung disease

Question 18

What are the characteristics of carbon and silica pneumoconioses?

Answer 18

Nodules initially form in upper lobes of lung. They contain the particles, macophages (to clear particles), and collagen.
Macrophages release mediators, attracting lymphocytes and fibroblasts that cause damage to alveolar cells and interstitium.
Macrophages can’t clear all particles, so fibrosis forms around them. This leads to hard, collagenous scars that may be pigmented.

Question 19

What is a granuloma?

Answer 19

Cluster of epithelioid histiocytes. A histiocyte is a macrophage, epithelioid means they have lots of cytoplasm and resemble epithelial cells - characteristically have a bean or footprint-shaped nucleus.
Surrounded by a ‘collar’ of lymphocytes and plasma cells.
Form when immune system isolates a non-degradable or particulate antigen.
Interferon Gamma is the key cytokine (gamma for granuloma)

Question 20

What causes granulomatous diseases?

Answer 20

Hypersensitivity (Pneumonitis) - Reaction to inhaled organic antigens or chemicals - e.g. farmers lung, bird fanciers lung, hot tub lung. In this case, removal of the antigen prevents disease progression.
Sarcoidosis. Idiopathic autoimmune systemic disorder characterised by formation of granulomata around lymphatics, bronchi and blood vessels. Granulomata may heal with hyalinisation and fibrosis, leading to pulmonary fibrosis.

Question 21

What are the characteristics of usual interstitial pneumonitis?

Answer 21

Repeated cycles of acute lung injury/alveolitis leads to progressive fibrosis.
Early stages - fibroblastic proliferation; late stages - collagenous, acellular scarred areas.
Both early and late stages are seen together (temporal heterogeneity), and some areas of the lung are spared (regional heterogeneity)
Median survival - 3 years, short term mortality >50%

Question 22

What are the characteristics of nonspecific interstitial pneumonitis?

Answer 22

Diagnosis of exclusion
Interstitial lymphocytes and plasma cells
Diffuse, but temporally homogenous interstitial fibrosis (i.e. fibrosis should be at the same stage where it exists).
Good prognosis compared to usual interstitial pneumotitis.