The lung functionally comprises 2 mechanisms: conduction and respiration. The conduction zone encompasses the movement and conditioning of inhaled air. The site of gas exchange and blood oxygenation involves the respiratory zone.
The conduction portion of the lung begins at the trachea and extends to the terminal bronchioles. Outside the lungs, the conduction system consists of the nasal cavities, nasopharynx, larynx, and trachea. Entering the lungs, the conducting portion spits into paired main bronchi. The bronchi begin a branching pattern, splitting next into lobar (secondary) bronchial branches and then again into segmental (tertiary) bronchi. The tertiary bronchi continue to divide into small bronchioles where the first change in histology takes place as cartilage is no longer present in the bronchioles. The end of the conduction portion of the lungs is at the final segment called the terminal bronchioles. The terminal bronchioles open into the respiratory bronchioles. This is the start of the respiration function of the lung.
The conducting portion provides the pathway for the movement and conditioning of the air entering the lung. Specialized cells collaborate to warm, moisturize, and remove particles that enter. These cells are the respiratory epithelium and comprise the entire respiratory tree. Most the respiratory epithelium is ciliated pseudostratified columnar epithelium. The following 5 types of cells are in this region:
The ciliated cells are the most abundant. They control the actions of the mucociliary escalator,, a major defense mechanism of the lungs that removes debris. While the mucus provided by the goblet cells traps inhaled particles, the cilia beat to move the material towards the pharynx to swallow or cough out.
Goblet cells, so named for their goblet-shaped appearance, are filled with mucin granules at their apical surface with the nucleus remaining towards the basilar layer. Goblet cells decrease in number as the respiratory tree gets progressively smaller and are eventually replaced by club cells (previously Clara cells) when they reach the respiratory bronchioles.
The basal cells connect to the basement membrane and provide the attachment layer of the ciliated cells and goblet cells. They may be thought of like the stem cells of the respiratory epithelium as they maintain the ability to potentiate ciliated cells and goblet cells.
Brush cells occasionally referred to as a type III pneumocyte cells are sparsely distributed in all areas of respiratory mucosa. Brush cells may be columnar, or flask-like and are identified by their squat microvilli covered apical layer–resembling a push broom or appropriately, a brush. No function has been officially assigned to the brush cells though there are many proposed mechanisms. One popular proposal suggests they have a chemoreceptor function, monitoring air quality, due to their associated with unmyelinated nerve endings. 
The bronchial mucosa also contains a small cluster of neuroendocrine cells, also known as Kulchitsky cells. They have neurosecretory type granules and can secrete several factors, including catecholamine and polypeptide hormones, such as serotonin, calcitonin, and gastrin-releasing factors (bombesin). Like brush cells, these neuroendocrine cells make up only a small portion of mucosal epithelium, around 3%.
Within the bronchial submucosa are submucosal glands composed of a mixture of serous and mucinous cells, similar to salivary gland tissue. Secretions are emptied into ducts and then on the bronchial mucosa. Older individuals may show oncocytic metaplasia of these glands. Smooth muscle bundles are present at all levels of the airway to allow for regulation of airflow. There are progressively fewer smooth muscle fibers progressing from bronchi to alveoli.
In the conducting zone, air is moistened, warmed, and filtered before it reaches the start of the respiratory zone at the respiratory bronchioles. The respiratory zone is where gas exchange occurs, and blood is oxygenated in exchange for carbon dioxide. As the respiratory tree transitions from the conducting zone at the terminal bronchioles, goblet cells diminish as club cells increase and the cartilage present in the conducting zone is absent once it reaches the respiratory bronchioles.
The acinus is directly distal to the terminal bronchioles and where the respiratory zone begins. The acinus is composed of respiratory bronchioles, alveolar ducts, and alveolar sacs. It is roughly spherical, resembling a bunch of grapes. Each respiratory bronchiole gives rise to several alveolar ducts and alveolar sacs–giving it that characteristic grape bunch appearance. The alveolar sacs are the ends of the respiratory tree and the site of gas exchange.
Alveolar epithelium is composed to type I pneumocytes, type II pneumocytes, and the occasional brush cell. Also present in the alveolar walls are the club cells and alveolar macrophages. The alveolar walls contain the pores of Kohn which allow communication between adjacent alveoli. This allows air to flow from one alveolus to another which may be beneficial if there is any blockage preventing air from entering alveoli through a direct route.
Type I pneumocytes make up roughly 90% to 95% of the alveoli. They are flat, squamous epithelia that resemble plate-like structures that allow gas exchange. Their thin membrane allows for easier gas permeability between the alveoli and the blood vessels. Despite being the primary method of respiration, they cannot replicate and are very susceptible to toxic injury.
Type II pneumocytes make up much of the remaining cell type in the alveoli, accounting for nearly 5%. Despite their low number, they are vital as they secrete pulmonary surfactant. The surfactant is necessary to maintain an open airway. It lowers the surface tension and prevents the alveoli from collapsing upon themselves during exhalation. By histology, these cells have foamy cytoplasm which results from surfactant that is stored as lamellar bodies. Type II pneumocytes are also mitotically active and can replace the easily damaged type I pneumocytes. Type II pneumocytes cells can be recognized on histology by their rounded shapes that bulge into the alveolar space.
Alveolar macrophages (or dust cells) may be free within the alveolar space or connected to the alveolar wall. If particles make it down to the acinus, the macrophages are the last defense and janitors of the respiratory epithelium. The black staining seen in lungs of smokers results from macrophages cleaning and sequestering particles that make their way inside.
The visceral pleura of the lung is lined by a mesothelial layer with underlying connective tissue and elastic fibers. An elastin stain may be used to identify the elastic layer.
Infant Respiratory Distress
Infant respiratory distress is the leading cause of death in premature babies. Type II pneumocytes produce surfactant starting around 20 weeks gestation, but it is not fully secreted until nearly 30 weeks of gestation. Without ample surfactant, premature infants cannot overcome the collapsing surface tension in the respiratory alveoli. Physicians hope to prevent infant respiratory distress when a patient goes into premature labor by offering the parent glucocorticoids. Glucocorticoids stimulate the production of surfactant in the fetus and may increase its production enough to help the infant overcome any potential respiratory distress. Testing for fetal lung maturity may be performed on the amniotic fluid by several methods, including the measurement of phospholipids in amniotic fluid (phosphatidylglycerol (PG) or lecithin-sphingomyelin ratio) and the lamellar body counts (LBC).
The most common cause of emphysema is smoking; although, it can be caused by repetitive inhalation of any foreign particulate material. Emphysema, or chronic obstructive pulmonary disease (COPD), is characterized by poor airflow and difficulty exhaling because of narrowing bronchioles and the destruction of the alveolar wall. The collapse of the alveoli results in a significant loss of surface area for gas exchange.
Healthcare professionals assume that the destruction of the alveolar wall is a result of excessive lysis of elastin in the interalveolar septum. The abundance of macrophages and neutrophils that migrate to the acinus due to an increase in particulate bring an equal increase of elastase and other proteases. Alpha 1-antitrypsin deficiency also causes emphysema because of an increase in elastin; however, in this disease, it is because the deficient antitrypsin usually inhibits elastin.
Cystic fibrosis may also cause chronic obstructive pulmonary disease. It is an autosomal recessive disease caused by a mutation to the CFTR gene on chromosome 7. This gene controls the Cl- channel protein involved in a variety of cells, including goblet cells in the lungs. The defective Cl-channel affects the viscosity of the mucus in the lungs, thickening it due to increased absorption of sodium (Na) and water from the lumen. The thickened mucus disrupts the mucociliary escalator filtration function of the lungs resulting in obstruction. One of the supportive treatments for cystic fibrosis breaks the disulfide bonds found in mucous plugs, thinning out the sputum so it can be pushed out by the respiratory cilia.
Heart Failure Cells
In heart failure, the heart's inability to move blood efficiently results in congestion of the lungs. The increase in pressure of the blood in the pulmonary vasculature results in erythrocytes passing into the alveolar septum. The erythrocytes are promptly taken up by resident alveolar macrophages. As the macrophages engulf any red blood cells present they are filled with hemosiderin and take on a brown granule appearance viewable under light microscopy with staining. Hemosiderin-laden macrophages are more accurately called siderophages and are not specific to a certain disease but may be present whenever blood cells enter the alveolus.
When staging primary carcinoma of the lung, it is important to identify invasion of the elastic layer of the visceral pleura. This finding will increase the T stage of the tumor. Since the elastic layer is difficult to visualize with routine stains, a special elastin stain may be used to demonstrate this finding.
|||Ganesan S,Comstock AT,Sajjan US, Barrier function of airway tract epithelium. Tissue barriers. 2013 Oct 1 [PubMed PMID: 24665407]|
|||Evans MJ,Van Winkle LS,Fanucchi MV,Plopper CG, Cellular and molecular characteristics of basal cells in airway epithelium. Experimental lung research. 2001 Jul-Aug [PubMed PMID: 11480582]|
|||Brody AR, The brush cell. American journal of respiratory and critical care medicine. 2005 Nov 15 [PubMed PMID: 16275741]|
|||Drozdov I,Modlin IM,Kidd M,Goloubinov VV, From Leningrad to London: the saga of Kulchitsky and the legacy of the enterochromaffin cell. Neuroendocrinology. 2009 [PubMed PMID: 18562785]|
|||Desplechain C,Foliguet B,Barrat E,Grignon G,Touati F, [The pores of Kohn in pulmonary alveoli]. Bulletin europeen de physiopathologie respiratoire. 1983 Jan-Feb [PubMed PMID: 6850150]|
|||Cordingley JL, Pores of Kohn. Thorax. 1972 Jul [PubMed PMID: 5075613]|
|||Bolt RJ,van Weissenbruch MM,Lafeber HN,Delemarre-van de Waal HA, Glucocorticoids and lung development in the fetus and preterm infant. Pediatric pulmonology. 2001 Jul [PubMed PMID: 11416880]|
|||Tomkiewicz RP,App EM,De Sanctis GT,Coffiner M,Maes P,Rubin BK,King M, A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog. Pulmonary pharmacology. 1995 Dec [PubMed PMID: 8819180]|
|||Zampieri FM,Parra ER,Canzian M,Antonângelo L,Luna Filho B,de Carvalho CR,Kairalla RA,Capelozzi VL, Biopsy-proven pulmonary determinants of heart disease. Lung. 2010 Jan-Feb [PubMed PMID: 19862572]|