pulmonology1 Flashcards
Pleura
Movement of the lungs within the thoracic cavity during inspiration and expiration is facilitated by a space between the two structures, the pleural space. The pleural space is created by the apposition of the inner lining of the chest wall, the parietal pleura, and the outer lining of the lung, the visceral pleura. A thin film of fluid separates the visceral and parietal pleura and acts as a lubricant. Disruption of this space either by air (pneumothorax), fluid (pleural effusion), or scarring can impair lung function.
Conducting Airways
The airways are a series of dichotomously branching tubes (i.e. a ‘parent’ airway divides into two ‘offspring’ airways) starting with the trachea and ending at the terminal bronchioles (the last conducting airway). On average there are 23 generations of airways in humans (from trachea to the last respiratory bronchiole). The first 16 are the conducting airways because they form a conduit for gas transfer to and from the respiratory exchange units of the lung. The structure of the airway wall changes depending on the generation of the airway. The walls are made up of three principal structures: the inner mucosal surface (epithelial cells, cilia, and goblet cells), the smooth muscle layer, and the outer connective tissue layer. Alterations in any of these layers can have an impact on airway resistance. Morphology of the airway wall changes as generation increases. Note specifically that the loss of cartilage in the outer tissue layer represents the transition from bronchi to bronchioles. Hence disease such as bronchitis and bronchiectasis refer to airways with cartilage whereas bronchiolitis affects the bronchioles or non-cartilagenous airways. Since the conducting airways by definition do not exchange gas, they are known as “anatomic deadspace.” Deadspace refers to parts of the lung that do not exchange gas. It can be anatomically defined or physiologically defined.
Gas-Exchange Regions
This region must permit efficient diffusion of oxygen and carbon dioxide across alveolar and capillary walls. The gas-exchange region (the acinus) begins distal to the terminal bronchiole and includes the respiratory bronchiole, the alveolar ducts, and the alveoli. The simple epithelium of the bronchioles gives way to two different types of alveolar epithelial cells, squamous lining cells (type I cells or pneumocytes) and secretory cells (Type II cells). Type I cells account for 95% of the alveolar surface area and fuse with the capillary endothelium to create a sufficiently thin membrane for adequate gas transfer. These cells can be injured in many diseases [such as the acute respiratory distress syndrome (ARDS)] impairing gas-exchange. Type II cells have two primary functions: 1) to repair or replace injured Type I pneumocytes, and 2) to secrete surfactant, a substance which lowers alveolar surface tension. Other cells found in the acinus (alveolar macrophages). Note that in the lung the pulmonary arteries (and arterioles) run with the bronchi (and bronchioles). Gas-exchange occurs at the capillary-alveolar interface. The pulmonary veins do not run with the airways but are more peripheral. Lymphatics run near the pulmonary arteries and veins to help cope with extravascular lung water.
Development of the Lung
The lungs develop from the lung bud of the gut tube endoderm. This bud eventually branches multiple times into the mesenchyme. The pulmonary circulation develops from the surrounding mesenchyme. The overlapping stages in embryogenesis on the lung include this initial branching, called the embryonic phase (26 days to 6 weeks gestation), the pseudoglandular phase lasting through 16 weeks where 14 more rounds of branching to the terminal bronchioles occurs, and the cannicular phase where the terminal bronchioles branch into respiratory bronchioles (to age 28 weeks). At about 26 to 28 weeks, if a premature infant is born, it has a reasonable chance of survival owing to the production of surfactant that begins at the end of the canalicular stage. Between 28 and 36 weeks, during the saccular phase, the respiratory bronchioles branch into terminal sacs and after 36 weeks, the alveolar phase occurs with maturation of the alveoli, increased surfactant secretion, etc. The lung continues to grow after birth into childhood (with growth occurring with formation of terminal sacs and then alveolarization taking place). Understanding lung development helps us understand why infants born after 36 weeks rarely have respiratory distress due to prematurity
Embryonic stage of lung development
at around 26 days to 6 weeks. The foregut endoderm extends into surrounding mesenchyme and 3 rounds of branching establish lung lobes. Initially asymmetric branching then a dichotomous branching pattern. This forms the proximal structure of the tracheobronchial tree to the level of the subsegmental bronchii and begins to fill bilateral pleural cavaties. Branching pattern determined by mesoderm. At branch points epithelia cell division stopped and collagen is produced. At developing buds, growth factors are produced to induce epithelial mitosis. Other mesodermal and epithelial factors stabilize and develop airways.
Pseudoglandular stage of lung development
6 to 16 weeks. 14 rounds of branching form terminal bronchioles. There is differentiation of conducting airway epithelium. It has a glandular appearance surrounded by mesenchyme. Formation of conduction airways is completed at end of this stage. The presence of cartilage, smooth muscle cells and mucous glands develop from the splanchnic mesenchyme
Canclicular stage of lung development
16 to 28 weeks. Terminal bronchiole divides into 2+ respiratory bronchioles. Surfactant production begins and increases as weeks progress. This stage is characterized by formation of respiratory bronchioles with delineation of pulmonary acinus. Initial development of pulmonary capillary bed. Expansion of airspaces at expense of mesenchyme. Fetal breathing is detected. Epithelial cell differentian beings and it is possible to survive but with respiratory distress problems.
Saccular stage of lung development
28 to 36 weeks. Respiratory bronchioles subdivide to produce terminal sacs (these continue to develop well into childhood. Distal growth and branching of terminal saccule with thinning interstitial space and decrease in cell proliferation. Now have type II and type I epithelial cells
Aveolar stage of lung development
36 weeks to early childhood (4 to 6 years). Lungs grows and alveoli mature: septea thin, single capillary network in alveolar wall, gas exchange unit established. Secondary septal formation. Presence of true alveoli. Type II cells proliferate and differentiate into type I cells. Lengthening and sprouting of capillary network. Fusion of the double capillary network and mature respiration surface for gas exchange.
Type I pneumocytes
90-95% by surface area but 33% by cell number (compared to Type II pneumocytes). Has a flat, thin squamous structure for gas diffusion. Poorly replicative. Form tight junctions with one another which prevent passage of large molecules
Type II pneumocytes
areclustered cuboidal cells that cover ~ 5% of the surface area of the lower area, but comprise ~ 2/3of all the cells in the lower airway(by cell number).Type II pneumocytes contain secretory cytoplasmic inclusions called lamellar bodies which secrete pulmonary surfactant. In addition to secreting surfactant,type II pneumocytes also act as stem cells. They are capable of mitotic division and replace damaged type I and II pneumocytes. The lower airway also contains several other cell types, including: Alveolar macrophages, Mast cells, Club cells (formerly known as Clara cells), and Lymphocytes. Neutrophilsare not normally found in the lower airway, but can be found in there in patients following anacute lung injury (ex: active smokers). In embryology, type II pneumocytes appear at 6 mongths
Surfactant
secreted by type II pneumocytes, acts to decrease alveolar surface tension, leading to an increase in compliance. Surfactants act to decrease surface tension in the alveoli, which ultimatelydecreases the work of inspiration (remember Laplace’s law). Surfactant synthesis does not begin until around week 26 of development. Mature levels of surfactant are not achieved until week 35 of development. Pulmonary surfactant is composed of dipalmitoyl phosphatidylcholine (a type of lecithin). A lecithin-sphingomyelin ratio of > 2.0 in amniotic fluid suggests that the fetal lungs are mature.
An acinus
refers to any cluster of cells that resembles a many-lobed berry, such as a raspberry (acinus is Latin for “berry”). The berry-shaped termination of an exocrine gland, where the secretion is produced, is acinar in form, as is the alveolar sac containing multiple alveoli in the lungs.
Lung embryology
Lung development begins in week 4 and continues until birth, with the majority of development takes place in the third trimester. The respiratory system arises from the embryonic endoderm in the pharyngeal and foregut region. Epithelial cells of primitive foregut invade the splanich mesenchyme. Primitive lung bud develops from an outpouching between the 4th and 6th brachial arches, called the laryngotracheal groove. The respiratory diverticulum is a ventral outgrowth of the foregut that grows anteriorly and inferiorly, developing into the: Trachea, Bronchi, and Bronchioles. Right and left lung bud push into primordial pleural cavity called the pericardioperitoneal. Portions of mesoderm from the paired pericardioperitoneal canals become the visceral and parietal pleura. As the lung buds develop, they push the visceral peritoneum outward expanding to meet the parietal peritoneum against the body wall, shrinking the pericardioperitoneal canals. As the lungs (and the heart) descend into the thorax, the pleuroperitoneal foramen closes. The downward growth of the lungs is halted from the liver. The lungs remain contained within the visceral peritoneum. The lungs develop through progressive division in a sequential order: Main bronchi, Bronchioles, Alveoli. The tracheoesophageal folds on either side of the respiratory diverticulum grow medially to become the tracheoesophageal septum, which separates the foregut into the laryngotracheal tube and the esophagus. The respiratory diverticulum maintains a small, superior communication with the distal pharynx, which will become the laryngeal inlet.
Pulmonary arteries
arise from the 6th aortic arch and muture into pulmonary arch. Pulmonary veins are out growths to left atrium.
General Overview of structure and Anatomical Terms of the Lungs
The lungs are contained within the pleural cavity and are connected via the trachea to the region of the larynx. The conduction system, beginning with the trachea, distributes air in up to about 20 generations of branching to the gas exchange system of the lung. Branching of the trachea to the left and right primary bronchi permits air to enter the left and right lungs, respectively. The primary bronchi branch to the secondary or lobar bronchi (three in the right lung, two in the left) that enter the five lobes of the lung (Upper right, middle right, and lower right, up- per and lower left). These then branch into segmental bronchi that respectively aerate individ- ual segments of the lung (10 in the right lung, 8 in the left). The medical relevance of segments is that each has its own air and blood supply and function as separate subunits. Should disease be restricted to one seg- ment, it can be surgically resected.
Pleura
The lung is contained in the pleural cavity and is covered by a thin elastic layer (the visceral pleura), which is com- prised of elastic fibrocol- lagenous tissue embed- ded with small amounts of smooth muscle, and contains nerves, lymphat- ics and blood vessels, covered by a surface layer of mesothelial cells.
The parietal pleura
lies against connective tissue that is continuous with the periosteum of the ribs and connective tissue of the intercostal muscles. The potential space between the pleural linings is normally negative in pressure relative to the atmosphere, hence, a puncture of the pleural cavity can lead to partial collapse of the lung.
Conduction System of the Lungs
The segmental bronchi further branch, giving rise to smaller bronchi, then to the bronchioles, which can further branch to terminal bronchioles which connect with the respiratory bronchioles of the exchange system.
Histology of the trachea and bronchi
The trachea contains about 20 “c-shaped” cartilagenous rings along its length, connected posteriorly by the trachealis muscle, whereas primary bronchi have segmented cartilagenous plates around their entire diameter. They are similar in their histologic structure, having an inner pseudostratified epithelial layer and a lamina propria that comprise the mucosa, an underlying submucosa of connective tissue, the cartilagenous layer and an adventitia connecting them to surrounding tissues. Larger bronchi contain a circumferential layer of smooth muscle, the muscularis, between the epithelial layer and the submucosa, which is not continuous in smaller bronchi or in the trachea. The tracheal and bronchial epithelium is similar. It is primarily comprised of ciliated epithelial cells, goblet cells, and basal cells. Also present are neuroendocrine cells, albeit in less abundance. The submucosae of the trachea and bronchi contain glands that contribute mucous and serous secretions to the mucosal surface.
Neuroendocrine cells
have small granules and secrete serotonin, bombesin, and other regulatory peptides. They sometimes cluster near nerve terminals and are thought to play roles in reflexive control of vascular or airway diameter.
Goblet cells
secrete mucins and other proteins which accumulate on the surface of the epithelium. A major proportion of incoming particulates bind to the sticky surface of the mucous layer, which therefore serves as the first line of defense against infection and congestion. The degree of hydration of the mucous layer is regulated by ionic channels. The ciliated cells contain 100-200 cilia which move in synchrony, the wave-like action continually pushing the mucous layer, in conveyor-belt fashion, toward the esophagus where it is swallowed. The basal cells are progenitor cells for the goblet and ciliated cells.
Mucosal associated lymphoid tissue
In addition, nodes of lymphocytes (mucosal-associated lymphoid tissue, or MALT) are present in the submucosa and serve as a second line of defense against infectious agents which might have obtained a “foothold” on the epithelial lining.
Bronchioles
Branching of bronchi leads to smaller air- ways which, when the diameter is about 1 mm, no longer have cartilage or glands, called bronchioles. Bronchioles have smooth muscle underlying the lamina pro- pria. They have ciliated cells and goblet cells in the epithelial layer and actively move mucous toward the larger bronchi. As bronchioles branch they give rise to a terminal bronchiole which leads to the ex- change system. Toward the exchange sys- tem, the terminal bronchiole epithelium contains comparatively more club cells, which secrete surface-active substances.