Pulmonary Pathophysiology II: Restrictive Diseases

Pulmonary Pathophysiology II: Restrictive Lung Diseases

• Restrictive lung diseases are characterized by decreased total lung capacity, preventing complete ventilation, and alveolar dysfunction.
• Normal FEV1/FVC ratios are observed; both inspiration and expiration are impaired.
• Total lung capacity is reduced, resulting in lower FVC and FEV1 values, but the ratio remains normal.
• Primarily caused by parenchymal (lung tissue) diseases, not airway issues.

Causes of Restrictive Lung Diseases

• Interstitial Lung Diseases:
  • Hypersensitivity pneumonitis
  • Exposure-induced pneumoconiosis (e.g., asbestosis, silicosis, coal workers' pneumoconiosis)
  • Sarcoidosis
  • Systemic lupus erythematosus (SLE)
  • Iatrogenic (e.g., methotrexate, amiodarone, nitrofurantoin)
  • Radiation pneumonitis
• Acute Respiratory Distress Syndrome (ARDS)
• Pulmonary Edema
• Pneumonia
• Empyema
• Pneumothorax
• Immunologic Mediated Diseases: (e.g., vasculitis)
• Neuromuscular Diseases: Affecting thoracic cage expansion (e.g., Guillain-Barre syndrome, myasthenia gravis, ALS)
• Pleural Effusions (caused by various conditions like pneumonia, heart failure, or cirrhosis)

Exposure-Induced Pneumoconiosis

• Pulmonary fibrosis results from alveolar macrophage-mediated phagocytosis, releasing pro-inflammatory cytokines and attracting immune cells and fibroblasts.
• Exposure to various substances can lead to these lung diseases, such as coal dust, silica dust, asbestos, and beryllium.
• Significant scarring and thickening of the alveolar membrane decrease gas exchange.

Hypersensitivity Pneumonitis

• Immune-mediated response to minuscule environmental antigens or biomolecular components of pathogens.
• Common triggers include mold/fungi in air conditioners, humidifiers, bird antigens, feline dander, and bacteria in certain farm environments.

Sarcoidosis

• Rare idiopathic multi-organ disease characterized by systemic inflammation primarily driven by macrophages and CD4 T cells.
• Macrophages accumulate, forming granulomas, and release pro-inflammatory cytokines, promoting interstitial fibrosis.
• Epidemiologically more prevalent in African-American females.
• Classically, granulomas hyper-produce vitamin D, leading to hypervitaminosis D and hypercalcemia.

Iatrogenic (Medication-Induced) Pneumonitis

• Multiple mechanisms, but most involve increased reactive oxygen species (ROS) formation and increased chemotaxis of innate immune cells, leading to pulmonary fibrosis.
• Specific drugs implicated include nitrofurantoin, methotrexate, Bactrim, amiodarone, cyclophosphamide, and hydralazine.
• Clinical symptoms might take months to manifest.

Acute Respiratory Distress Syndrome (ARDS)

• Syndrome characterized by diffuse, acute inflammatory lung damage.
• Causes include alveolar wall fibrosis and impaired gas exchange, surfactant inactivation, and increased vascular permeability resulting in pulmonary edema.
• Two primary types are direct (due to direct pulmonary consequences) and indirect (due to extra-pulmonary causes)

Pathophysiology of ARDS

• Inactivated surfactant, decreased alveolar recruitment, reduced gas exchange.
• Increased chemotaxis of innate immune cells, leading to alveolar damage.
• Increased vascular permeability causing edema reduced gas exchange and impaired oxygen diffusion into the blood stream.
• Increased scarring (fibrosis) of alveolar capillary membrane.

Pneumothorax

• Air in the pleural space, leading to lung collapse.
• A medical and surgical emergency, requiring immediate management due to its potential for compromise of venous return to the heart and pulmonary compromise.
• Multiple subtypes, including trauma (traumatic PTX) if it occurs from wounds, tension PTX if air trapping causes high pressure and secondary spontaneous PTX if this damage happens from infection.

Pneumothorax (Dx/Tx)

• Diagnosis crucial using Chest X-ray.
• Management usually involves immediate needle decompression and chest tubes to remove air and allow lung re-expansion.

Thoracic Cage Diseases

• Diseases affecting the thoracic cage prevent expansion, reducing the alveoli's propensity to fill with air.
• Diseases commonly include myasthenia gravis, Guillain-Barré syndrome, muscular dystrophies, and kyphoscoliosis.

Pulmonary Embolism (PE)

• Clot within the pulmonary arterial circulation from a distant site (typically deep vein thrombosis).
• Risk factors include obesity, pregnancy, smoking history, prolonged recumbency, and certain medical conditions.
• Symptoms can range from silent presentation to severe right-sided chest pain with shortness of breath, hemoptysis, and hemodynamic instability.
• Significant cardiopulmonary compromise and potential heart failure or hemodynamic instability due to large embolus in part of the lungs.
• Possible diagnosis using specialized CT imaging.

Pathogenesis (PE)

• Occlusion of pulmonary perfusion resulting in reduced gas exchange.
• Release of pro-inflammatory cytokines.
• Potential for thrombus worsening through platelet stimulation and further embolism formation.