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INTRODUCTION

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While the primary function of the respiratory system is gas exchange, the lungs serve several additional physiologic roles. Some of the nonrespiratory functions of the lungs include defense against inhaled particles and pathogens, filtration of blood-borne substances, metabolism of endogenous and exogenous substances, and provision of a vascular reservoir.

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CLEARANCE

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Inhaled particle size determines lung removal method. Larger particles (>3 μm) are captured within the airway’s mucus layers. These particles are propelled away from the lungs by cilia and later expectorated or swallowed. Smaller particles are removed by exhalation or macrophage ingestion. Smoking, dry gas inspiration, extreme temperature exposure, dehydration, inhaled anesthetics, opioids, atropine, and alcohol decrease cilia activity. High-dose ketamine and fentanyl have been shown to increase cilia activity.

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PROTECTION AGAINST INFECTION

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Multiple defense mechanisms against pathogen inhalation exist. Like inhaled particles, pathogens may be directly captured by the pulmonary mucous membrane, propelled cephalically by cilia, then expectorated or swallowed. For pathogens that escape the mucus membrane, chemical inactivation is used to render pathogens harmless. Type II alveolar epithelial cells produce surfactant, which increases bacterial cell wall permeability, leading to pathogen death. Additionally, surfactant stimulates macrophage migration, production of reactive oxygen species, and synthesis of immunoglobulin and cytokines. Lactoferrin contributes to bacterial destruction by blocking iron uptake and impairing proliferation of bacteria. Defensins are peptides that cause bacterial cell wall defects and stimulate respiratory epithelium chemokine release. If pathogens escape direct and chemical removal, the humoral and cellular immune systems are the final line of respiratory defense. The humoral immune system consists of IgA in the upper respiratory tracts and IgG in the lower respiratory tracts. IgA is responsible for preventing bacterial binding and invasion in the respiratory mucosa. IgG surrounds the pathogen and enhances phagocytosis by macrophages. The cellular immune response increases pathogen phagocytosis by respiratory endothelial release of adhesion molecules, chemokines, cytokines, growth factors, and extracellular matrix proteins.

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FILTRATION

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The lungs filter systemic venous return of blood and prevent the passage of endogenous and exogenous substances to systemic circulation. The lungs prevent passage of most microemboli to the arterial system while maintaining gas exchange for moderate to small clots. Abundant anastamoses throughout the pulmonary circulation maintain gas exchange despite the microemboli present. Inefficiencies in filtration lead to thrombi bypassing the lungs, such as when a patient has a patent foramen ovale. The pulmonary endothelium produces substances that both lyse clots and promote clot formation. The lung is rich in plasmin activator, which catalyzes the conversion of plasminogen to plasmin, which then promotes the conversion of fibrin to fibrin degradation products. The lung contains heparin, which prevents future clot formation. Additionally, the lung contains prothrombotic agents such as thromboplastin, which converts prothrombin to thrombin.

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METABOLISM

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The lungs facilitate many metabolic processes. The lungs metabolize noradrenaline, serotonin, atrial natriuretic peptide, and endothelins, but ...

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