Mechanics of Respiration I & II - 2023 - Syllabus.pdf

R. A. Zoeller & A.W. Young Mechanics of Respiration & Ventilation Learning Objectives: 1) Describe the organization and structure of the airways, and differentiate between the conducting zones and the respiratory zones. 2) Describe the mechanisms by which the volume of th...

R. A. Zoeller & A.W. Young Mechanics of Respiration & Ventilation Learning Objectives: 1) Describe the organization and structure of the airways, and differentiate between the conducting zones and the respiratory zones. 2) Describe the mechanisms by which the volume of the thorax enlarges during inspiration and decreases during expiration. 3) Explain why the pressure in the intrapleural space (PIP) is negative. 4) Plot a compliance curves for the lung. 5) Identify the factors that influence the functional residual capacity (FRC). 6) Describe surfactant and its importance in lung function. 7) Graphically represent and explain pressures (Palveolar and Pintrapleural) and volume changes in the lung during a respiratory cycle. 8) Identify the determinants of airway resistance, and explain the causes of dynamic compression of the airways. 9) Define anatomic and physiologic dead space. 10) Identify specific ventilation volumes and capacities. 11) Understand gas laws as they apply to respiration INTRODUCTION Pulmonary ventilation (the bulk flow of air in and out of the lungs) and blood circulation through the lungs are coordinated to allow for adequate exchange of O2 and CO2 across the alveoli of the lungs. In other words, the lungs function to get O2 into the blood for the body’s metabolic needs and to remove CO2 generated during metabolism. A third major function of ventilation, through modulation of the CO2 levels, is to regulate blood pH. If fact, our ventilation rate (the amount of air we move into and out of the lung per minute) is modulated, in part, to maintain a normal blood pH. ANATOMY The lungs: We have two lungs, the right and the left (Figure 1). These are lined with a layer of cells and connective tissue called the visceral pleura. The lungs are surrounded by the chest wall, which contain the rib cage and the respiratory musculature (the exterior and interior intercostal muscles) and the diaphragm. These are lined with the parietal pleura. The space between the two pleura is known as the intrapleural space. It is filled with about 10-15 ml of intrapleural fluid. Importantly, there is no Figure 1. A simplified illustration of the lung/thoracic air in this space, only fluid. Each lung is lying in cavity a cavity separated from the other lung. This is a closed space (not open to the atmosphere or other body fluids). 1 R. A. Zoeller & A.W. Young The airways: We are concerned with the physical mechanisms involved in moving air in and out. There is a bulk flow of air through a conduit system from the nose, mouth, pharynx, larynx, and trachea into the alveoli. The airways making up each lung are shown in Figure 2. As the trachea enters the chest cavity, there is a bifurcation into the first “generation” of bronchi, entering either the left or right lung. Once in the lung, the airways continue to divide (bifurcate) to generate 23 “generations” of airways. As air is taken into the lungs, it must first go through the conducting zone. This is the first 16 generations of airways which include the trachea, bronchi, and bronchioles. No exchange of gases occur between the blood and lung in this region. The alveoli are little sacs that are only one cell layer thick. It is the alveoli that provide the surface for diffusive gas exchange between the lung gases and blood (hence the rest of the body). Alveoli begin to appear, and gas exchange begins to occur, in the 17th generation of airways and below. Thus, the respiratory zone of the lungs is made up of all airway generations with alveoli (divisions 17-23 comprising Figure 2: Schematic view of the bronchial tree the respiratory bronchioles, and alveolar ducts & and corresponding airways. alveolar sacs). There are about 300 million alveoli making up a surface of approximately 70 square meters (the size of a tennis court) providing a huge surface area for gas exchange. Airway structure: As can be observed in a lateral view (Figure 3) the trachea has significant structural support; it is surrounded by cartilage shaped like a horseshoe. It is therefore, difficult to collapse, it can withstand significant external pressure. The bronchi have some support: they have broken rings or plates of cartilage surrounding them. They are resistant to closure or collapse due to external pressure, but not as resistant as the trachea. The bronchioles have no supportive cartilage Figure 3. Airway structures holding them open or patent; thus the bronchioles are subject to collapse. Therefore, it is important that the pressure inside these lower airways is greater than the pressure surrounding them. 2 R. A. Zoeller & A.W. Young MECHANICS OF VENTILATION To simplify the mechanics, the chest wall includes the intercostal muscles, accessory muscles, ribs, and diaphragm. Upon inspiration, the external intercostals and diaphragm contract, the diaphragm moves downward and the chest wall moves outward. The chest cavity has increased in size (volume) during this inspiration. The external intercostals muscles are coordinated during inspiration. Contraction moves the lower rib toward the upper rib. The main direction of expansion of the rib cage is forward and lateral (this is known as the pump handle model; Figure 4). Fig. 4 During inspiration when the external intercostal muscles contract (left), the ribs are pulled upward and forward (far right). They rotate on an axis where the tubercle and head of the rib are joined. This rotation axis is angled so that both the lateral and anteroposterior diameters of the thorax increase. (This is known as the pump handle model.) Contractions of the internal intercostals pull the ribs downward (center and right figures) and cause the chest cavity to decrease in size. Now that the chest cavity has increased in volume what is happening to the lung? The lung is following the movements of the chest wall because the intrapleural space does not expand in size. It is not a space at all but is filled with a few milliliters of fluid. Because the fluid does not expand to any great degree the lung must move with the chest wall. The cohesive forces between the fluid and pleural walls cause them to move as one. How does the lung move with the chest wall? The lung has elastic properties allowing expansion and elastic recoil. Elastin and collagen fibers, arranged in a lattice structure, provide part of the lung’s elasticity. It is the overall lattice structure that renders the elasticity; no single fiber stretches. Forces and pressures: At rest, the forces imposed by the lung and chest wall oppose and balance one another. If not attached to the lungs, the chest wall would spring outward (outward recoil). Similarly, if not attached to the chest wall, the lung would recoil inward, collapsing to a volume of baseball (inward recoil). Thus, the outward recoil forces of the chest wall and the inward recoil forces of the lungs pull on the intrapleural space in opposite directions. Therefore, the pressure in the intrapleural space (the intrapleural pressure or PIP) is slightly negative (sub-atmospheric). Throughout the discussion we shall refer to atmospheric pressure at sea level (1 Atmosphere = 760 mm Hg = 760 Torr = 1,033 cm H2O) as relative 0. We will use cm H2O in the examples below. At the end of a quiet expiration (Figure 5A) the lung and chest wall are at equilibrium lung volume, called the functional residual capacity (FRC). This is the lung volume at which the tendency 3 R. A. Zoeller & A.W. Young of the lung to recoil is exactly balanced by the tendency of the chest wall to expand. No muscular contraction is occurring at this volume. Any change in volume from FRC requires the contraction of respiratory muscles. At FRC, the typical intrapleural pressure is – 5 cm H2O (5 cm H2O below the atmospheric pressure). This pressure can be measured in a subject using an esophageal balloon. The esophagus has such soft tissues that intrapleural pressures are transmitted to a balloon that is inflated enough to touch the esophageal walls. The balance of forces at FRC is lost if air is introduced into the intrapleural space by, for example, a knife wound. Since atmospheric pressure is greater than intrapleural pressure, air rushes into the intrapleural space, and PIP rises until it equals atmospheric pressure. The result is that the chest wall expands outward and the lung recoils inward, collapsing (Figure 5B). This Figure 5. The tendency of the lung to recoil is balanced by that of the rib cage to spring out. As a result the intrapleural condition is known as a pneumothorax or pressure is subatmospheric. Pneumothorax allows the lung to collapsed lung. collapse and the thorax to spring out. The negative pressure in the intrapleural space at FRC is made less negative by any factor decreasing the inward recoil of the lung tissue as with age, and in conditions such as emphysema (a condition in which alveoli are distended due to loss of elastic fibers). PRESSURE CHANGES DURING THE NORMAL RESPIRATORY CYCLE Let us consider the pressure changes and consequent air flow during a normal respiratory cycle below. The most important term in this discussion is the “transpulmonary pressure” (TPP). It is defined as the difference between the alveolar pressure (PALV; the pressure inside the airways and alveoli) and the intrapleural pressure (PIP). [TPP = PALV - PIP.] The transpulmonary pressure is also sometimes referred to as the “distending pressure”. During a normal breathing cycle in a healthy individual, the TPP is always positive. This is important to keep the compressible airways open, allowing proper airflow. Inspiration Prior to lung inflation (at FRC) the alveolar pressure (PALV) is zero, and the intrapleural pressure (PIP) is about -5 cm H2O (Figure 6A). The transpulmonary pressure (TPP) is, therefore: PALV - PIP = 0 – (-5) = +5 cm H2O. During inspiration (Figure 6B), the volume of the chest (and lungs) increases when the inspiratory muscles (diaphragm and external intercostals) contract. Flattening of the diaphragm and elevation of the ribs, which results in chest expansion, pulls open the lungs. Intrapleural pressure, which is transmitted to the outside of all alveoli because of their physical interdependence, falls as the expanded lung increases its recoil force away from the chest wall. Alveolar pressure also falls during chest expansion (increase in volume), and it generates a pressure gradient that promotes flow of air into the lungs. With lung expansion, the transpulmonary (distending) pressure (PALV - PIP) increases. End inspiration is the state of the lung after pressure gradients between gases in the alveoli and the outside air are dissipated, and the flow of gases into the lung has stopped. The lung is at the largest volume of the respiratory cycle, and in the example of Fig. 6C the transpulmonary pressure has risen to +9 cm H2O [ TPP = PALV – PIP = 0 – (-9) = +9 cm H2O ]. 4 R. A. Zoeller & A.W. Young Figure 6. Relative pressure changes during respiration. Distending pressures of the airways are boxed. During inspiration, the expansion of the lung lowers alveolar pressure relative to atmospheric pressure and causes gas to flow into the lung. During expiration, the recoil of the lung and chest wall raises alveolar gas pressure and reverses the flow of air. The increases in lung volume during inspiration are also associated with increases in the distending pressure of the lung. Similarly, during expiration, lung volume and lung distending pressures fall. Note that in “B” and “D”, the lung volumes must be the same because they have the same distending pressures, i.e., +6 cm H2O. (For this analysis we are neglecting hysteresis and assuming that the compliance of the lung is the same during inspiration and expiration.) Expiration: At the end of inspiration the nerves to the diaphragm and inspiratory intercostal muscles cease firing, and the muscles relax. The lungs, expanded beyond FRC, pull the chest wall back toward the resting position at FRC. During the decrease in thoracic volume, air in the alveoli becomes compressed, exceeds atmospheric pressure and flows into the atmosphere. During normal quiet breathing, expiration is completely passive. Expiration becomes active during exercise or forced expiration. During forced expiration, the internal intercostals contract, draw the ribs downward and pull the chest wall in. Contraction of the abdominal muscles increases intra-abdominal pressure and forces the diaphragm upward. These actions actively decrease chest volume. The volume changes and resulting changes in pressures during a normal respiratory cycle can be represented graphically (Figure 7). Notice that the pressures are in mm Hg, not cm H2O (that’s how the book chose to express pressure). A change of 1 mm Hg in pressure is equivalent to a change of 1.36 cm H2O. Importantly, notice that the alveolar pressure is always greater than the intrapleural pressure throughout the respiratory cycle. Figure 7. Changes in pressure during normal tidal breathing. 5 R. A. Zoeller & A.W. Young COMPLIANCE We see the changes in volume that occur with changes in transpulmonary pressure. Essentially, when we talk about “compliance” (C) of the lung, we’re talking about how much of a change in the transpulmonary pressure is required to increase the lung volume. In other words, how much effort it takes to inflate the lung. Compliance is determined by the inward recoil forces of the lung. The stronger these forces, the less compliant the lung is (more effort will be required to inflate the lung). Figure 8 depicts a compliance curve of an excised lung. The lung is inflated by decreasing the pressure surrounding it by known amounts (the X axis) and measuring the increase in lung volume (Y axis). This is similar to the decreasing intrapleural pressure observed during inflation of the lung (Fig. 6). C = ∆V CL = ∆VL ∆P ∆(PALV -PIP) Note: where (PALV -PIP) = transpulmonary pressure Figure 8: Measurement of the pressure-volume curve of excised lung. The lung is held at each pressure for a few seconds while its volume is measured. The curve is nonlinear and becomes flatter at high expanding pressures. (West- Resp. Physiol) The compliance is the slope of this curve at any point. The higher the compliance the easier it is to expand the lungs at any given pressure. With low lung compliance the intrapleural pressure must be made more negative than usual. That is, during inspiration in order to expand the lung one must use increased respiratory effort. Note that the compliance curve is not linear; the curve becomes flatter at the higher volumes indicating the lung is less compliant when it is filled with air (the recoil forces of the lung increase). Also note that the lung with no expanding pressure (P=0) still has air inside. It is not completely collapsed because there is some air that gets trapped inside. There are 2 major factors that contribute to the recoil forces of the lung: elastic recoil and surface tension Elastic recoil: The airways and alveoli are held together and interconnected by an elastic meshwork of fibers made up of the proteins collagen and elastin. When the inspiratory muscles contract, this meshwork can be stretched and the lung volume can increase. When the inspiratory muscles relax, this elastic network 6 R. A. Zoeller & A.W. Young pulls back, decreasing the lung volume. You can compare this to a nylon stocking, which can be stretched to fit the foot and leg, but snaps back to its original form when you take it off. The further you stretch this meshwork, the more difficult it becomes to further stretch it (i.e. you need more force or an increased transpulmonary pressure). Disease can modify the compliance of the lung. Emphysema is a condition where the fibrous meshwork has been destroyed or greatly damaged. This reduces the elastic recoil and makes the lungs much more compliant. This may seem like a good thing, but it’s not. The fibrous meshwork interconnects all the airways, pulling on them and thus, helping to keep them open. When this meshwork is damaged, airways can easily collapse and stop airflow. Interstitial fibrosis causes thickening of the lung’s interstitium and therefore decreases compliance of the lung. Structural changes in the lung can alter the compliance of the lung. If there is an increase in blood volume in the pulmonary capillaries there is decreased compliance. Also, in the case of pulmonary edema (interstitial fluid buildup) there is decreased compliance. As we age our lungs become more compliant, probably due to gradual loss of the elastic fibers. Surface Tension: A second determinant of compliance is the surface tension of the lung. Alveoli are covered with fluid that sits between the alveolar gas and the alveolar epithelium. Attractive forces between water molecules (surface tension) cause the alveoli to tend to shrink (to minimize surface area) and resist further expansion of the lung. LaPlace's Law P = 2T r Figure 9: With decreasing radius the pressure exerted by an alveolus increases. Where T= surface tension, r = radius & P = pressure exerted by the alveolus The law of LaPlace describes the pressure required to maintain a certain size alveolus is proportional to the surface tension, and inversely proportional to the radius. Thus, given the same surface tension, the pressure exerted by a smaller alveolus is greater than that exerted by a larger alveolus. So, smaller alveoli have a tendency to empty into larger alveoli. This can be overcome by reducing the surface tension using surfactant. Pulmonary surfactant is produced by the Type II alveolar cells starting at the 26th week of gestation. Deep breathing stimulates the production of surfactant. Surfactant is comprised mostly of dipalmitoyl phosphatidylcholine (DPPC; a phospholipid) and surfactant proteins (SPA, SPB, SPC & SPD). Importantly, surfactant lowers surface tension in a 7 R. A. Zoeller & A.W. Young manner that is inversely related to the surface area, so as the alveoli increase in size, surface tension increases, counteracting the effects of increased radius (see LaPlace’s Law). The mechanism behind this phenomenon is not well understood. In premature infants the lack of surfactant leads to Respiratory Distress Syndrome or Hyaline Membrane Disease which is the 2nd leading form of death in infants. The increase in surface tension (due to the lack of surfactant) decreases compliance of the lungs, making it difficult or impossible for the infant to inspire properly. If a premature birth is anticipated the administration of cortisol to the mother increases the rate of maturation of cells producing surfactant. AIRWAY RESISTANCE AND AIR FLOW Now that we understand the forces involved in the pressure-volume changes in the lung, we can consider how these mechanical forces allow ventilation. Ventilation or bulk flow of air (usually expressed in L/min) occurs between atmosphere and alveoli from a region of high total pressure to a region of low pressure. According to the Poiseuille equation (as already considered for laminar flow of fluids). F = PALV - Patm = ∆P 1) R α Viscosity of air R R 2) R α Length of the airway 3) R α 1/r4 where r = radius of airway Figure 10: Location of the chief site of airway resistance. The location of the site of airway resistance can be located in the graph above. Twenty-five to fifty percent of the total resistance to airflow is in the upper airways (nose, nasopharynx, larynx). Normally the greatest resistance in the bronchial tree occurs in the medium sized bronchioles (up to 7th generation) and not in the very small bronchioles because there are so many of them. There are so many parallel pathways from the branching of the pulmonary tree and the resistance is: 1 1 1 1 ── = ─── + ─── + ─── RT R1 R2 R3 8 R. A. Zoeller & A.W. Young Usually resistance is low such that small pressure differences (transpulmonary pressure differences) of less than