The pulmonary system exists on the most basic level to facilitate gas exchange from environmental air into the circulatory system. We breathe in oxygen, which diffuses into the blood for systemic circulation and ultimately produces ATP for use as energy on a cellular level, and we breathe out Carbon dioxide along with other metabolic byproducts from the body. This process is facilitated by the respiratory tract organs, which include the nose, throat, larynx, trachea, bronchi, and lungs. The lungs are further divided into five separate lobes, two on the left and three on the right. Each lobe is made up of small sacks of air called alveoli. There are approximately 300 million alveoli in healthy lungs. It is at the surface of alveoli where diffusion from air into pulmonary arterioles occurs.
The overarching mechanism of breathing to ventilate alveoli breaks down into four aspects: lung compliance, chest wall compliance, airway resistance, and rate of ventilation. These components work to facilitate the principle that as the lung expands, the air pressure in the alveoli drops, causing air to move into the lungs. As lung volume decreases, pressure increases, forcing air out of the lungs.
Lung compliance is based on the elastic properties of the supporting tissues surrounding the alveoli and the surface tension of the alveoli. The mathematical equation is:
Elastic properties are best exemplified by rubber bands. When stretched, how easily and forcefully does the tissue return to its original configuration? Elasticity is controlled by the content of elastin (stretchy fibers) and collagen (stiff structural fibers) within lung tissue. The surface tension of the alveoli describes the ease at which the alveoli are allowed to expand. A high surface tension tends to cause alveoli to collapse and not expand with aeration. Surface tension is reduced by type II pneumocyte cells within the lung which produce a liquid secretion composed of approximately 40% dipalmitoylphosphatidylcholine, 40 % other phospholipids, and 20 % other lipids.
Chest wall compliance is similarly based on elastic properties. However, this is more of a balance of chest wall elastic recoil, which tries to increase lung volume, and the lung’s elastic properties, which are trying to decrease lung volume.
Airway resistance is based on the physics principle of Ohm’s law where:
Looking at the math involved, it is important to make some basic assumptions. The viscosity of air does not change, and the length of the airway does not change. This leaves the only variable in the equation that physiologically adjusts to be the diameter of the airway. The resistance of breathing, therefore is primarily controlled by the airway diameter. Diameter change has three primary etiologies: intraluminal, such as secretions blocking the airway; intramural, such as edema or the interstitial space; or extraluminal, such as loss of interstitial collagen and elastic traction tissues.
Finally, the rate of ventilation increases the exchange rate of oxygen from the environmental air into the lung and removes carbon dioxide out of the lung to maintain favorable concentrations of these gasses to facilitate diffusion. 
Diffusion is the principle that substances will passively move from an area of higher concentration into an area of lower concentration. Ventilation functions to create an environment where oxygen is in high concentration in the lung and carbon dioxide is in lower concentration in the lung, relative to pulmonary capillaries. However, equally important to diffusion rate is the solubility of a gas in liquid, gas density, and available surface area for diffusion to occur within the lung. Carbon dioxide is highly soluble in physiologic conditions; therefore, oxygen is the limiting factor of concern here. Gas densities are negligible in physiologic conditions. Total available surface area, however, is a very important variable in pulmonary pathology. As total alveolar surface area decreases relative to available arteriolar perfusion the available potential space to diffuse oxygen into blood decreases. A malformation in any of these parameters may lead to hypoxia. The primary notation for monitoring the diffusion gradient of oxygen is the A-a gradient. A-a oxygen gradient is calculated as:
PaO is measured by arterial blood gas, while PAO is calculated using the alveolar gas equation:
Where FiO2 is the fraction of inspired oxygen (0.21 at room air), Patm is the atmospheric pressure (760 mmHg at sea level), PH2O is the partial pressure of water (47 mmHg at 37 degrees C), PaCO2 is the arterial carbon dioxide tension, and R is the respiratory quotient. The respiratory quotient is approximately 0.8 at steady state but varies according to the relative utilization of carbohydrate, protein, and fat.
Aberrant function of the pulmonary system will inherently manifest in the form of hypoxia. There are four main classifications regarding the etiology of hypoxia: hypoventilation, right-to-left shunt, diffusion limitations, and ventilation/perfusion mismatching (V/Q mismatch).
Essentially, any pathology that decreases ventilation of the alveoli will lead to a hypoventilation defect. These can include central nervous system depression or malformation from neurologic deficit, Guillaine-Barre, amyotrophic lateral sclerosis, or drug overdose where respiratory drive is decreased, obesity hypoventilation (excess weight of the chest prevents proper inflation), muscular weakness, or poor chest elasticity secondary to rib fracture or kyphoscoliosis.
A ventilation-perfusion mismatch is as the name states, an imbalance between available ventilation and available arteriolar perfusion for oxygen to diffuse into circulation. Within a normal lung, there is variation throughout the tissue in response to oxygen and capillary demand. In the base of the lung, perfusion is relatively greater than ventilation leading to a V/Q which is lesser than in the apices. Bronchoconstriction in lung tissue normally occurs to reduce ventilation to poorly perfused lung regions, and likewise, vasoconstriction in capillary arterioles normally occurs in poorly ventilated regions of the lung. Combined, these mechanisms work to balance the V/Q ratio so that the net effect is heterogeneous ventilation and perfusion with minimal pathological dead space or shunting. In disease states such as pulmonary vascular diseases, interstitial disease, or obstructive lung disease, the ratio of available lung ventilation to capillary perfusion is skewed, netting hypoxic environments.
A right-to-left shunt is a pathological alternate pathway of circulation that allows deoxygentated blood to bypass the lungs from the right side of the heart to the left side of the heart. Subsequently, oxygenation does not occur. Shunting is an example of extreme V/Q mismatching. Two main types of shunt exist: anatomical and physiological. Anatomical shunts include intracardiac shunts, pulmonary arteriovenous malformations (AVMs), and hepatopulmonary syndrome. A physiological shunt exists when nonventilated alveoli remain perfused, thus functioning as a shunt even though there is not an anatomic anomaly. Examples include pneumonia and acute respiratory distress syndroime.
Diffusion limitation exists when movement of oxygen from alveoli to pulmonary vasculature is impaired. This etiology is characterized by fibrosis of the lung and parenchymal destruction of alveoli leading to a decreased surface area of alveoli tissue. Often diffusion abnormalities are coexistant with V/Q mismatching and are most prevelant undxer exercise conditions. During rest, blood flow through the lung arterioles is slow enough to allow for proper diffusion, regardless of an increased A-a gradient. However, under exercise conditions, cardiac output increases. When this occurs, there is less time for oxygenation to occur in the lung which leads to transient hypoxia. Examples of limited diffusion disease include lung fibrosis and chronic obstructive pulmonary disease. 
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