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Nonrespiratory Functions of the Lung Pulmonary Defense Mechanisms Nonrespiratory Functions of the Pulmonary Circulation Metabolic Functions of the Lung Pulmonary Defense Mechanisms Air Conditioning Olfaction Filtration and Removal of Inspired Particles Filtration and Removal of Inspired Particles Filtration of Inspired Air Removal of Filtered Material Reflexes: Cough and Sneeze The Mucociliary Escalator Mechanisms of the Terminal Respiratory Units Alveolar Macrophages Other Methods Of Particle Removal or Destruction Figure 10-1 sphenoidal sinus turbinates adenoid tissue orifice of auditory tube uvula epiglottis antrum ethmoidal sinus septum middle meatus turbinates antrum Sphenoidal sinus Turbinates Adenoid tissue Orifice of auditory tube Uvula Ethmoidal sinus Epiglottis Tongue Turbinates Antrum Septum Filtration of Inspired Air Hairs at the inlet filter particles greater than 10-15µ Nasal turbinates force inspired air to pass in narrow streams so particles pass close to either the nasal septum or mucosa of the turbinates and impinge directly on mucosa or settle by gravity Particles greater than 10µ are almost completely removed in the nose, along with some smaller ones Particles between 2 - 10µ usually settle on the mucuslined walls of the trachea, bronchi, and bronchioles Particles between 0.3 and 2.0µ and all foreign gases reach the alveolar ducts and alveoli Particles less than 0.3µ in diameter usually remain as aerosols and are almost entirely expired Particles removed may include: silica, asbestos, inert dust, bacteria Mucociliary Escalator Cilia line entire respiratory tract (except part of pharynx, anterior 1/3 of nose, and the terminal respiratory units) Beat 600-900 times/min Appear to be coordinated so sheet of mucus (containing trapped foreign particles) secreted by goblet cells and mucous glands is propelled toward the pharynx where is it swallowed or expectorated Mechanism of control is not well understood. Nerves do not appear to be involved. Inhaled irritants may slow down or "paralyze" cilia Figure 10-2 Alveolar Macrophages Large mononuclear ameboid cells - scavenge the alveolar surface and engulf inhaled particles Contain lysosomes capable of killing bacteria Many other functions, including secretion of components of immune and inflammatory responses such as cytokines, arachidonic acid derivatives, enzymes, and growth factors Life span 1-5 weeks Appear to emigrate to the sheet of mucus on the walls of terminal bronchioles and "ride" up to larger airways Figure 10-3 Other Methods of Particle Removal or Destruction Reach the mucus sheets by upward movement of the alveolar fluid lining Penetrate into the interstitial space for phagocytosis by tissue histiocytes, and/or entrance into the lymphatic channels Particles may also be destroyed by surface enzymes (lysozymes, lactoferrin) or removed by immunologic reactions (interferon, complement, etc.) mucociliary escalator pulmonary arteriole Figure 10-4 bronchial-associated lymphoid tissue terminal bronchiole centripetal lymphatics respiratory bronchiole alveolar sac bronchoalveolar junction pleura alveolar macrophage cell and/or particle pathway particle fluid absorption pathway Integrated System for Defense of the Respiratory Tract Natural Mechanical Defenses Filtration and impaction remove particles Sneeze, cough, and bronchospasm expel particles Epithelial barriers and mucus limit particle penetration Natural Phagocytic Defenses Effected by airways, interstitial, and alveolar macrophages; polymorphonuclear leukocytes Phagocytosis of particulates, organisms, and debris Microbicidal and tumoricidal activities Degradation of organic particles Integrated System for Defense of the Respiratory Tract Acquired Specific Immune Defenses Humoral immunity Effected by B lymphocytes Biologic activities mediated by specific antibody Augments phagocytic and microbicidal defense mechanisms Cell-mediated immunity Effected by T lymphocytes Biologic activities mediated by: Delayed-type hypersensitivity reaction T cell cytotoxicity Augments microbicidal and cytotoxic activities of macrophages Mediates subacute, chronic, and granulomatous inflammatory responses Nonrespiratory Functions of the Pulmonary Circulation Reservoir for left ventricle Filter to protect the systemic circulation Fluid exchange and drug absorption Figure 10-5 200 arterial pressure, mmHg 100 0 120 SVC pressure, cmH2O 0 220 260 distal PA pressure, 230 mmHg 0 aortic flow, ml/s 300 200 100 0 PA flow, ml/s 300 200 100 0 balloon occlusion ECG Metabolic Functions of the Lungs Uptake or conversion by lungs of chemical substances in mixed venous blood Formation of chemical substances in lungs and release for local use: surfactant, histamine, serotonin, leukotrienes, PAF, PG’s, etc. Release into blood of substances stored in pulmonary tissues or cells, including macrophages: bradykinin, histamine, serotonin, PGE2, PGF2 , heparin, etc. Uptake or Conversion by the Lungs of Chemical Substrates in Mixed Venous Blood SUBSTANCE IN MIXED VENOUS BLOOD RESULT OF A SINGLE PASS THROUGH THE LUNG Prostaglandins E1, E2, F2 Prostaglandins A1, A2, I2 Leukotrienes Serotonin Acetylcholine Histamine Epinephrine Norepinephrine Isoproterenol Dopamine Bradykinin Angiotensin I Angiotensin II Vasopressin Oxytocin Gastrin ATP, AMP Almost completely removed Not affected Almost completely removed 85-95 % removed Inactivated by cholinesterases in blood Not affected Not affected Approximately 30% removed Not affected Not affected Approximately 80% inactivated Approximately 70% converted to Ang II Not affected Not affected Not affected Not affected 40 - 90% removed Figure 10-6 Air TM Aqueous subphase MAC LB MVB Type I cell Type I cell G ER Interstitium Type II cell Basal membrane