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Alveoli represent the major sites of gas exchange. Their presence increases the surface area of the lung to maximize gas exchange, much like villi and microvilli increase the absorptive surface area of the digestive tract. For alveoli to carry out their function efficiently, they must be both a dynamic and stable system. The lung parenchyma must be able to expand and recoil during inspiration and expiration, and the air-blood barrier must be thin to allow for gas exchange to occur. Also, cells of the alveoli must be healthy to form a barrier to keep the lungs dry and be able to regenerate if they are damaged.

COPD (chronic bronchitis and emphysema) COPD is a chronic and irreversible obstructive respiratory disease characterized by a reduction in the elasticity of the lungs, leading to air trapping and symptoms, including difficulty breathing. COPD is most commonly caused by smoking, which leads to the loss of alveolar epithelial cells, alveolar macrophages, and endothelial cells via apoptosis. When alveolar macrophages become disrupted, they are unable to phagocytize bacteria, leading these patients to have increased susceptibility to pulmonary infections. Additionally, alveolar macrophages release high levels of cytokines that promote inflammation, leading to the recruitment of neutrophils and monocytes that also damage the lung via inflammation.[9][10] Asthma Asthma is another chronic obstructive respiratory disease, but in contrast to COPD, it is reversible. This disease characteristically demonstrates airway hyperreactivity and inflammation. Alveolar macrophages are responsible for regulating pro- and anti-inflammatory responses in the lungs, so it may be possible that these cells play a role in asthma.[11][12] Cystic Fibrosis CF is an autosomal recessive disorder characterized by the dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) located on type II pneumocytes and other body areas. The CFTR protein is responsible for the production of sweat production, digestive fluids, and mucous. Specifically, in the lungs, loss of function of the CFTR protein causes mucous lining the alveoli to become thick instead of thin. Additionally, there is an increased number of alveolar macrophages leading to an upregulation of inflammation. Thick mucus and inflammation clog the airways and can cause difficulty breathing, coughing, and pulmonary infections.[13] Pulmonary Fibrosis Pulmonary fibrosis is a restrictive disease of the lower airway characterized by fibrosis and inflammation of the alveoli. Autoimmune or allergic reactions, environmental particulates, infection, or mechanical damage can initiate this disease process, starting with pulmonary injury. After the initial insult, inflammation in the airways results. Subsequent tissue repair and contraction lead to fibrosis and reduced ability to expand alveoli. In an attempt to replace damaged alveolar epithelium, type II pneumocytes become hyperplastic and proliferate and differentiate chaotically.[3][14] Pneumoconioses

Pulmonary fibrosis is a restrictive disease of the lower airway characterized by fibrosis and inflammation of the alveoli. Autoimmune or allergic reactions, environmental particulates, infection, or mechanical damage can initiate this disease process, starting with pulmonary injury. After the initial insult, inflammation in the airways results. Subsequent tissue repair and contraction lead to fibrosis and reduced ability to expand alveoli. In an attempt to replace damaged alveolar epithelium, type II pneumocytes become hyperplastic and proliferate and differentiate chaotically.[3][14] Pneumoconioses Pneumoconioses are interstitial lung diseases caused by the inhalation of organic and inorganic particles that are phagocytized by alveolar macrophages. Subsequently, they secrete cytokines that cause inflammation in the lungs. This process leads to particular diseases, such as coal workers’ pneumoconiosis, silicosis, and asbestosis. When alveolar macrophages engulf asbestosis, it is referred to as ferruginous bodies within the cytoplasm, which appear dumbbell-shaped.[2] Tuberculosis TB occurs when alveolar macrophages phagocytize the bacteria Mycobacterium tuberculosis. M. tuberculosis has developed ways to avoid being destroyed once phagocytized and accumulates within alveolar macrophages. Also, alveolar macrophages attempt to wall off the infection by encircling it, forming multinucleated giant cells (or Langerhans giant cells). Surrounding them are T-cells, and it’s the communication between the alveolar macrophages and the T-cells via TNF-alpha and IFN-gamma that form a granuloma. It is important to note that damage to these alveolar macrophages caused by another infection can trigger the release of M. tuberculosis and cause recurrent tuberculosis.[2] Sarcoidosis Sarcoid is a condition that forms non-caseating granulomas in the lungs of patients by the joining of alveolar macrophages in an attempt to wall off the infectious process. Alveolar macrophages in sarcoidosis also secrete vitamin D, which contributes to the hypercalcemia seen in this disease.[2] Acute Respiratory Distress Syndrome (ARDS)

Sarcoid is a condition that forms non-caseating granulomas in the lungs of patients by the joining of alveolar macrophages in an attempt to wall off the infectious process. Alveolar macrophages in sarcoidosis also secrete vitamin D, which contributes to the hypercalcemia seen in this disease.[2] Acute Respiratory Distress Syndrome (ARDS) ARDS is characterized by non-cardiogenic pulmonary edema caused by some inflammatory condition that causes capillary endothelial leakage. The fluid eventually resolves, but some patients may develop residual fibrous tissue.[15] In infant respiratory distress, premature infants cannot overcome the collapsing surface tension of their alveoli because their type II pneumocytes have not been able to secrete surfactant fully. Bronchioloalveolar or alveolar carcinoma of the lung accounts for about 5% of lung cancers. In addition to bronchial mucous cells and Clara cells, alveolar carcinoma can arise from type II pneumocytes as well.[16] Left-sided congestive heart failure leads to the backup of blood within the pulmonary vasculature. When this happens, erythrocytes can pass into the alveolar septum, where they are taken up by alveolar macrophages, which become filled with hemosiderin. When looking at these cells under the microscope, they take on a brown granule appearance due to the hemosiderin within the cytoplasm of these cells. The name for these cells is hemosiderin-laden macrophages.[17] Influenza pneumonia results from the influenza virus directly infecting alveoli epithelial cells, causing inflammation and alveoli damage. Alveolar macrophages play a role in protecting these pneumocytes from injury by the influenza virus.[18]