Definition
Restrictive lung diseases are usually chronic, diffused, lung interstitial diseases, usually effecting the most peripheral and delicate interstitium of the alveolar walls.
What is pulmonary Interstitium?
Pulmonary interstitium is composed of basement membranes of the alveolar epithelial cells, vascular endothelial cells, and the tissue between them, mostly made of elastic fibers, collagen, fibroblasts that make more elastic fibers, smooth muscle cells, mast cells, and sometimes mononuclear cells.
In the peripheral parts of the lung where the alveoli are numerous the interstitium is thin and delicate. Sometimes composed of only the two basement membranes fused together.
Figure: Components of the interstitium. Note the alveolar macrophage is not a part of this interstitium. Also, in peripheral areas the interstitium is minimal causing the two basement membranes to fuse.
Hallmark of the restrictive lung diseases
Reduced compliance of the lungs. That is, the lungs are so stiff that they cannot expand easily. Patient has to exert more energy to pull air in the lungs. This is dyspnea.
Damage to the alveolar epithelium and pulmonary vessels hinders gas exchange leading to hypoxia.
Causes of the restrictive lung diseases
- Inhaled irritants for example: dust, blood borne toxins, unknown antigens,
- Chest wall abnormalities
- Parenchymal pathologies
- Most diseases in this category, however, are of unknown origin.
Radiographic changes
Chest X-Ray shows diffused infiltration by small nodules, ground glass appearance, or irregular lines.
Progression of the restrictive lung diseases
With chronic progress of restrictive diseases, patients can develop pulmonary hypertension, cor pulmonale, and respiratory failure.
It is important to note that the end stage of all diseases in this category is diffused interstitial pulmonary fibrosis. Which leads to the pulmonary hypertension cor pulmonale and respiratory failure.
Categories of the restrictive lung diseases can be divided into
- Clinicopathologic
- Histological
The major categories for both the clinicopathologic and histological restrictive lung diseases are
- Fibrosing restrictive lung diseases. Some examples ares:
- Interstitial Pneumonia
- Collagen vascular disease
- Pneumoconiosis
- Drugs, radiations
- Granulomatous restrictive lung diseases. Examples include:
- Sarcoidosis
- Hypersensitivity Pneumonia
- Eosinophilic restrictive lung diseases. For example restrictive lung diseases due to:
- Smoking
- Bronchiolitis
- Desquamative interstitial pneumonia
Pathogenesis
Core Pathology
Pathogenesis of the restrictive lung diseases always includes alveolitis.
Alveolitis is the earliest manifestation of most of the interstitial pulmonary diseases.
Immune cells gather in the alveolar walls and alveolar spaces. They induce and amplify alveolar inflammation.
If mild, the injury resolves and the normal architecture is reestablished. But if the cause of the injury persists then the chronic inflammatory process starts resulting in the fibrosis and restrictive lung disease.
Cellular events during the progress of the restrictive lung diseases
Persistent injury causes activation of the macrophages. Macrophages secret chemoattractants like IL8 (interleukin 8) and LTB4 (leyukotrine B4). These substance recruit and activate neutrophils.
Oxidants and proteases released by the activated macrophages and neutrophils cause injury to the alveolar epithelium and breakdown the interstitial connective tissue.
Damaged epithelial cells result in reduced Type I pneumocytes and proliferation of the type II pneumocytes. These cells also secret chemical substances for example macrophage chemotactic protein 1. This protein recruits more macrophages which in turn amplify the inflammatory process. Pneumocytes also release Platelet derived growth factors (PDGF) and Transforming Growth Factor Beta (TGFB) which activate the fibroblasts and increase fibrosis.
Active macrophages also release fibrogenic factors. These factors include transforming growth factor Beta, fibroblast growth factor, and platelet derived growth factor (PDGF). These growth factors attract fibroblasts and activate them. Activated fibroblasts trigger the repair and scarring process resulting in the fibrosis.
With persistent injury, lymphocytes, macrophages, and neutrophils become involved. These active cells cause parenchymal damage. Resulting inflammation causes fibroblasts to proliferate and make more elastic and collagen fibers. Local damage also causes scarring. The result is interstitial fibrosis.