Pulmonary Pathophysiology II - Restrictive Lung Diseases, Other Pulmonary Diseases PDF

Pulmonary Pathophysiology II: Restrictive Lung Diseases, Other Pulmonary Diseases Joshua Mastin, MD South College School of Pharmacy Restrictive Lung Diseases Restrictive Lung Diseases are characterized by diminished total lung capacity, prevention of complete ventilation, and alveolar dysf...

Pulmonary Pathophysiology II: Restrictive Lung Diseases, Other Pulmonary Diseases Joshua Mastin, MD South College School of Pharmacy Restrictive Lung Diseases Restrictive Lung Diseases are characterized by diminished total lung capacity, prevention of complete ventilation, and alveolar dysfunction. Classically: NORMAL FEV1/FVC; in other words, both inspiration and expiration are adversely affected! Since TOTAL lung capacity is decreased, FVC is decreased along with FEV1, thus making the ratio NORMAL (normal doesn’t equate to “good”, however, since both inspiratory and expiratory capacities are decreased!) Restrictive Lung Diseases typically occur as a result of parenchymal (i.e., lung tissue) disease rather than airway pathophysiology. Restrictive Lung Diseases Restrictive lung diseases classically result in decreased lung compliance. RECALL: Compliance = metric of how well the lungs are able to: 1) expand within the thoracic cavity during inspiration, and 2) expel air during expiration. Decreased lung compliance = inability of the lungs to expand appropriately during inspiration +/- inability of the lungs to utilize elastic recoil to expel air during expiration “Stiff lung” alveoli attempt to expand during inspiration, but since the parenchyma is stiff, the alveoli cannot completely expand results in decreased oxygenation, increased retention of carbon dioxide Causes of Restrictive Lung Disease Diseases which cause pulmonary fibrosis: Interstitial Lung Diseases: Hypersensitivity Pneumonitis Exposure-Induced Pneumoconiosis (Asbestosis, Silicosis, Coal Worker’s Pneumoconiosis) Sarcoidosis Systemic Lupus Erythematosus (SLE) Iatrogenic (Methotrexate, Amiodarone, Nitrofurantoin) Radiation Pneumonitis Acute Respiratory Distress Syndrome (ARDS) Pulmonary Edema Pneumonia, Empyema Pneumothorax Neuromuscular diseases which affect thoracic cage expansion (Guillain-Barre Syndrome, MG) Immunologic Mediated Diseases (Vasculitis, sarcoidosis) Pneumothorax (Tension PTX) Pleural effusions (which can be due to pneumonia, heart failure, cirrhosis, etc.) Neuromuscular Disorders (Myasthenia Gravis, ALS, Guillain-Barre Syndrome) Exposure-Induced Pneumoconiosis Pulmonary Fibrosis occurs as a result of alveolar macrophage-mediated phagocytosis, followed by release of pro-inflammatory cytokines and the attraction of immune cells and fibroblasts: Coal exposure (coal worker’s pneumoconiosis) due to accumulation of coal mine dust Silica exposure (silicosis)- rock quarry workers, stonemasons, glass and cement company workers Asbestos (Asbestosis)- Mineral processing, factories, old houses; can cause mesothelioma (exceedingly rare, but has the potential to metastasize; contrary to popular belief, does NOT only occur in those who work on naval ship yards, as late night TV would have you believe) Beryllium (Berylliosis)- electronics workers; largest potential to cause malignancy Pulmonary fibrosis scarring of lung parenchymaincrease in thickness of the alveolar membrane decreased gas exchange Exposure-Induced Pneumoconiosis Post-mortem lung sample, Coal Worker’s Pneumoconiosis Hypersensitivity Pneumonitis Immune-mediated responses to minuscule antigens Antigens can be either environmental exposures OR biomolecular components (cell surface proteins, glycolipids, cell wall/membrane phospholipids, fragments) of infectious pathogens Common antigens include: Mold/fungi residing in air conditioners, humidifiers Antigens from birds (feathers, excrement) Fur/Dander from feline species Bacteria which reside in unkempt silos, milking sheds, compost areas in farms Sarcoidosis Sarcoidosis is a rare, idiopathic disease characterized by systemic, multi-organ disease characterized by inflammation which is primarily driven by macrophages. Macrophages and CD4 T cells (what flavor?) become hyperactivated and accumulate together. Macrophages join together to become granulomas, large-scale centers which release pro-inflammatory cytokines and promote large amounts of interstitial fibrosis. Epidemiologically, more common in African-American females Classically, granulomas hyper-produce Vitamin D, resulting in hypervitaminosis D (increased presence of vitamin D in the bloodstream) Results in hypercalcemia, hypercalciuria (the form which is produced by granulomas is the 1,25-dihydroxyvitamin D isomer, which is ACTIVE and can penetrate the glomerular filtrate) Management: Corticosteroids are FIRST LINE!  Sarcoidosis Bilateral Hilar Lymphadenopathy Cutaneous Sarcoidosis (lymph node swelling), a classic finding associated with Sarcoidosis Iatrogenic (Medication-Induced) Pneumonitis Multiple possible mechanisms, depending on the drug involved, but the vast majority involve increased reactive oxygen species (ROS) formation and increased chemotaxis of innate immune cells  pulmonary fibrosis Drugs commonly implicated: Nitrofurantoin Methotrexate, Bactrim (Trimethoprim-Sulfamethoxazole) Amiodarone Cyclophosphamide Hydralazine Clinical symptoms may not manifest for months! Questions???? Acute Respiratory Distress Syndrome (ARDS) Acute Respiratory Distress Syndrome (ARDS) is a syndrome characterized by diffuse, acute inflammatory damage to the lungs, resulting in: Alveolar wall fibrosis, resulting in impaired gas exchange between the alveoli and pulmonary capillaries Surfactant inactivation, resulting in decreased alveolar recruitment Significantly increased vascular permeability, resulting in significant pulmonary edema Two primary types: Direct ARDS usually due to direct pulmonary consequences Chest wall trauma (penetrating or blunt force), Pneumonia (aspiration, community acquired, etc.), acute and robust exposure to environmental/chemical substrates which carry the risk of pulmonary toxicity, drowning Indirect ARDS usually due to extra-pulmonary causes of significant inflammation Sepsis, Acute Pancreatitis, Transfusion-associated lung injury, Coagulopathies Requires unique approach to mechanical ventilation to manage! Patients need increased PEEP positive end-expiratory pressure (think of this as “blowing air into a balloon to inflate it); increases the expansion and Anterior Chest X Ray--> recruitment of smaller alveoli over a period of time significant pulmonary edema, diffuse airspace disease ARDS, Pathophysiology Inactivated surfactant decreased recruitment of alveoli decreased number of alveoli involved with gas exchange Increased Chemotaxis of Innate Immune Cells (neutrophils, macrophages) increased leukotriene, pro-inflammatory cytokine release alveolar damage Increased vascular permeability (secondary to increased pro-inflammatory cytokine expression) increased fluid extravasation (edema) into the alveolar capillary membrane decreased oxygen diffusion into the bloodstream, decreased expiration of carbon dioxide Increased recruitment of fibroblasts increased scarring (fibrosis) of the alveolar capillary membrane + intra-alveolar Pneumothorax “Pneumothorax”= air in the thorax/chest MEDICAL AND SURGICAL EMERGENCY!!!!! Multiple subtypes, but most involve: Trapping of air within the pleural space (outside the alveoli), which compresses the lungs and raises intrathoracic pressure. This increase in intrathoracic pressure decreases venous return to the heart and causes pulmonary compromise via lung collapse. Etiologies: Trauma (traumatic PTX) Wounds which allow air into the thorax but does not allow it to exit (tension PTX) Infections which destroy the alveoli and release air into the pleural space (secondary spontaneous PTX) Pneumothorax Tension PTX on CXR; notice the darker appearing “bleb” which projects down the majority of the lung, not appearing to be sequestered to any particular lobe Pneumothorax Diagnosis: Chest x-ray is KEY; usually won’t have time to do anything else due to the acuity of the situation. Management: For Tension PTX immediate needle decompression – a large bore needle inserted into the affected side to remove excessive air and decrease intrathoracic pressure Mid-clavicular line, second intercostal space… For most cases chest tubes to remove excessive air and to allow for lung re-expansion Thoracic Cage Diseases Diseases which affect the thoracic cage prevent thoracic cage expansion decreased propensity for alveoli to fill with air Mostly neuromuscular diseases/myopathies Myasthenia Gravis Guillain-Barre Syndrome Muscular Dystrophies Kyphoscoliosis Pulmonary Embolism (PE) Clot within the pulmonary arterial circulation which embolizes (travels) from a distant site (usually from a focus of thrombosis, such as DVT’s in the lower extremity venous system) Epidemiology: Affects a multitude of Americans, but most common factors which increase risk include: Obesity Pregnancy Smoking history History of prolonged recumbency (happens commonly in truck drivers) History of thrombophilias/hypercoagulable states OCP’s, Factor V Leiden, Antiphospholipid Syndrome Recent surgery or delivery of infant Noncompliance with anticoagulant therapy Venous Stasis of the lower extremities Pulmonary Embolism (PE) Pathophysiology: Embolism occlusion of perfusion to a particular portion of the lungs. If occlusion is large enough (approx. 50% of the vessel or more) significant cardiopulmonary compromise due to right heart strain heart failure, hemodynamic instability Embolus can also release pro-inflammatory cytokines such as thromboxane A2, which stimulates platelets to further coagulate and either worsen the clot OR form a new embolism which can travel elsewhere to cause ischemia Pulmonary Embolism (PE) Clinical Presentation: OFTEN SILENT; DEADLY, however, so do not underestimate it! In some patients severe right sided chest pain with shortness of breath; pain is usually knife-like, constant… may have small hemoptysis (coughing up blood) PE + hemodynamic instability (significantly decreased blood pressure) = obstructive shock Pulmonary Embolism (PE) CT Angiogram, revealing a large pulmonary embolus QUESTIONS???