Lactology Foundation

Lung in Health and Disease

The lung is part of the respiratory system and consists of conducting airways, blood vessels, and gas exchange units with alveolar gas spaces and capillaries

The neural control of the respiratory system includes the brain cortex and medulla, the spinal cord, and peripheral nerves that innervate the skeletal muscles of respiration, airways, and vessels. The airways of the respiratory system include the upper airway—the nose, pharynx, and larynx—where inspired air is humidiied and particulate matter is iltered. The intrathoracic airways continue down the trachea to the carina where the mainstem bronchi branch deining the right- and left-sided airways. Bronchi continue to branch into smaller airways (bronchioles) that eventually take on gas exchange capacity and end in alveolar sacs. Both pulmonary arteries and veins and lymphatics follow the branching patterns of the airways. The lung also has systemic circulation via the bronchial arteries. The bony structure of the chest wall protects the heart, lungs, and liver, and the lungs are maintained in an inlated state by mechanical coupling of the chest wall with the lungs. The skeletal muscles of respiration include the diaphragm and the accessory muscles; the latter are important when disease causes diaphragm fatigue.
The lung is a complex organ with an extensive array of airways and vessels arranged to eficiently transfer the gases necessary for sustaining life. The organ has an immense capacity for gas exchange and can accommodate increased demand during exercise in healthy individuals. In lung disease, however, as exchange becomes compromised, the host’s activities and function become increasingly compromised. The most dramatic consequence of acute and chronic abnormalities in lung function is systemic hypoxemia, which causes tissue hypoxia in multiple other organs.
In addition to gas exchange, the lungs have other functions, such as defense against inhaled infectious agents and environmental toxins. The entire cardiac output passes through the pulmonary circulation, which serves as a ilter for blood-borne clots and infections. Additionally, the massive surface area of endothelial cells lining the pulmonary circulation has metabolic functions, such as conversion of
angiotensin I to angiotensin II. Lung disorders are common and range from well-known conditions such as asthma and chronic obstructive pulmonary disease (COPD) to rarely encountered disorders such as lymphangioleiomyomatosis.
LUNG DEVELOPMENT

The lung begins to develop during the irst trimester of pregnancy through complex and overlapping processes that transform the embryonic lung bud into a functioning organ with an extensive air way network, two complete circulatory systems, and millions of alveoli responsible for the transfer of gases to and from the body. Lung development occurs in ive consecutive stages: embryonic, pseudoglandular,
canalicular or vascular, saccular, and alveolar postnatal. During the embryonic stage (between 21 days and 7 weeks’ gestation), the rudimentary lung emerges from the foregut as a single epithelial bud surrounded by mesenchymal tissue. This stage is followed by the pseudoglandular stage (between 5 and 17 weeks’ gestation), during which repeated extensive branching forms rudi-mentary airways, a process called branching morphogenesis. Coinciding with airway formation, new bronchial arteries arise from the aorta.
The canalicular stage (between 17 and 24 weeks’ gestation) is characterized by the formation of the acinus, differentiation of the acinar epithelium, and development of the distal pulmonary circulation. Through the processes of angiogenesis and vasculogenesis, capillary networks derived from endothelial cell precursors are formed, extend from and around the distal air spaces, and connect with the developing pulmonary arteries and veins. By the end of this stage, the thickness of the alveolar capillary membrane is similar to that in the adult.
During the saccular or prenatal alveolar stage (between 24 and 38 weeks’ gestation), vascularized crests emerging from the parenchyma divide the terminal airway structures called saccules. Thinning of the
interstitium continues, bringing capillaries from adjacent alveolar structures into close apposition and producing a double capillary network. Near birth, capillaries from opposing networks fuse to form a single network, and capillary volume increases with continuing lung growth and expansion.
During the alveolar postnatal stage (between 36 weeks’ gestation and 2 years of age), alveolar development continues, and maturation occurs. The lung continues to grow through the first few years of childhood with the creation of more alveoli through septation of the air sacs. By age 2 years, the lung contains double arterial supplies and venous drainage systems, a complex airway system designed to generate progressive decreases in resistance to airlow as the air travels distally, and a vast alveolar network that eficiently transfers gases to and from the blood.
The processes that drive lung development are tightly controlled, but mishaps occur. Congenital lung disorders include cystic adenomatoid malformation of the lung, lung hypoplasia or agenesis, bullous
changes in the lung parenchyma, and abnormalities in the vasculature, including aberrant connections between systemic vessels and lung compartments (e.g., lung sequestration) and congenital absence
of one or both pulmonary arteries. In children without congenital abnormalities, lung disorders are uncommon, except for those caused by infection and accidents.
Congenital lung disorders are rare compared with the number of infants born annually with abnormal lung function as a result of prematurity. In premature infants, the type II pneumocytes of the lung are underdeveloped and produce insuficient quantities of surfactant, a surface-active substance produced by speciic alveolar epithelial cells that helps to decrease surface tension and prevent alveolar collapse. This disorder is called neonatal respiratory distress syndrome (RDS). The treatment of neonatal RDS is administration of exogenous surfactant and corticosteroids to enhance lung maturation. To sustain life while allowing maturation, mechanical ventilation and oxygen supplementation are required but may promote the development of bronchopulmonary dysplasia.

PULMONARY DISEASE
Epidemiology
Diseases of the adult respiratory system are some of the most common clinical entities confronted by physicians. According to the Centers for Disease Control and Prevention data for 2017, chronic lower respiratory diseases, inluenza or pneumonia, and cancer (including lung cancer) are among the top 10 causes of death due to medical illnesses in the United States. COPD is a leading cause of both death and disability in the United States. At a time when the age-adjusted death rate for other common disorders such as coronary artery disease and stroke is decreasing, the death rate for COPD continues to increase. More than 16 million Americans are estimated to have COPD, but the number is expected to rise because COPD takes years to develop and the incidence of cigarette smoking (the most common etiologic factor for COPD) is staggering. In 2017, more than 34.3 million Americans were daily smokers and 16 million Americans had a smoking-related illness. The true disease burden of COPD is much greater than these numbers indicate. Other pulmonary conditions are also common. Asthma affects 8% of adults and 9.5% of children in the United States. The prevalence, hospitalization rate, and mortality rate related to asthma continue to increase. In 2016, there were 257,000 hospital visits related to pneumonia and almost 50,000 deaths. Sleep-disordered breathing affects an estimated 7 to 18 million people in the United States, and 1.8 to 4 million of them have severe sleep apnea. Interstitial lung diseases are increasingly recognized, and their true incidence appears to have been underestimated. For example, idiopathic pulmonary ibrosis, the most common of the idiopathic interstitial pneumonias, affects 85,000 to 100,000 Americans annually.These conditions affect males and females of all ages and races. However, a disproportionate increase in the incidence, morbidity, and mortality related to lung diseases exists for minority populations.
This inding is true for COPD, asthma, certain interstitial lung disorders, and other diseases. Although these differences point to genetic differences among these populations, they also indicate differences in culture, socioeconomic status, exposure to pollutants (e.g., inner city living), and access to health care.

Classification
Lung diseases are often classiied on the basis of the affected anatomic areas of the lung (e.g., interstitial lung diseases, pleural diseases, airways diseases) and the physiologic abnormalities detected by pulmonary function testing (e.g., obstructive lung diseases, restrictive lung diseases). Classiication schemes based exclusively on physiologic factors are inaccurate because distinctly different disorders with different causes, consequences, and responses to therapy have similar physiologic abnormalities (e.g., restriction from pulmonary ibrosis versus restriction from neuromuscular disease).

The obstructive lung diseases have in common a limitation of airlow, called an obstructive pattern, as determined by pulmonary function testing. Obstructive lung diseases include COPD, asthma, and bronchiectasis. The interstitial lung diseases are less common disorders and are more dificult to categorize because they include more than 120 distinct entities, some of which are inherited, but most of which are with out an obvious cause. These disorders are characterized by a restrictive physiologic condition due to decreased lung compliance and small lung volumes, which is the reason they are often referred to as restrictive lung disorders (e.g., idiopathic pulmonary ibrosis). However, not all interstitial lung diseases exhibit a purely restrictive pattern on pulmonary function testing. They may have airlow limitation as a result of small airway involvement (e.g., sarcoidosis, cryptogenic organizing
pneumonia). In the pulmonary vascular diseases, involvement of the pulmonary vasculature causes increased pulmonary vascular resistance. These diseases range from disorders caused by obstruction to blood flow as a result of blood clots (e.g., pulmonary embolus) to disorders characterized by tissue remodeling and obliteration of blood vessels by vascular remodeling (e.g., pulmonary arterial
hypertension).Disorders of respiratory control include conditions in which extrapulmonary abnormalities cause respiratory system dysfunction and abnormal ventilation. Included are sleep disorders such as obstructive sleep apnea and neuromuscular system disorders such as myasthenia gravis and polymyositis, in which ventilatory abnormalities result from poor excursion of the respiratory muscles.
Disorders of the pleura, chest wall, and mediastinum are classiied as such because they affect these structures. Infectious agents, commonly viruses and bacteria, cause infectious diseases of the lung. Neoplastic disorders of the lung include benign (e.g., hamartomas) and malignant (e.g., lung carcinoma) tumors, which can affect the lung parenchyma or its surrounding pleura (e.g., mesothelioma).