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Physiology 2130
Anita Woods

Respiratory System Section 10.1 – Objectives • Explain the basic anatomy of the respiratory system. • Describe the anatomical relationship of the lungs to the chest wall, pleural membrane, and diaphragm. • Explain the significance of a low intrapleural pressure (compared to the alveolar pressure) and what happens during a pneumothorax. • Define Boyle's Law. • Describe the processes of inspiration and expiration and the muscles involved in each event. • Explain the characteristics that contribute to elasticity in the lungs. • Define and explain compliance. • Define surface tension and explain why it tends to cause the lungs to collapse. • Explain the function of surfactant. • Describe all the static lung volumes and capacities as measured using a spirometer. • Define pulmonary ventilation. • Explain the significance of alveolar ventilation and how it differs from pulmonary ventilation. • Describe how partial pressures are calculated. • Describe the diffusion of gases across the respiratory membrane. • Describe the partial pressures of gases throughout the circulatory system. • Describe the transport of O 2n the blood. • Describe the process of erythropoiesis, the function of the hormone erythropoietin and the result of a decrease in oxygen delivered to the kidney.Also, describe the structure of hemoglobin. • Explain the effects of PO 2 PCO , 2H, and temperature on the oxyhemoglobin curve. • Describe the transport of CO i2 the blood. • Describe the origin and regulation of respiration through central and peripheral chemoreceptors. Section 10.2 – Introduction • The functions of the respiratory system include the following:  The transport of oxygen from the air into the blood  The removal of carbon dioxide from the blood into the air  The control of blood acidity (pH)  Temperature regulation  Forming a line of defense to airborne particles 1 Section 10.3 –Anatomy • The lungs are located in the thoracic cavity and are surrounded by the rib cage and the diaphragm. • The airways consist of the nasal cavity and the mouth, which join together at the pharynx. • The pharynx leads into the larynx or voice box, which then becomes the trachea. • The trachea divides into two main bronchi (left and right), which continually divide into smaller and smaller bronchioles. • These bronchioles continually divide and eventually end in the alveoli, which are the site of gas exchange in the lung. • Larynx: aka voice box, is where sound is produced by the passage of air. This sound is then modified by the lips and tongue to produce the final vocal noises. • Trachea: aka the wind pipe, large conducting airway of the respiratory system. It has wings of cartilage that help to hold it open so air can move in and out with ease. Trachea branches into the left and right primary bronchi. • Right (right main bronchus) and left bronchi: There are two primary bronchi; one in each lobe of the lung. Bronchi divide into smaller and smaller airways which become the bronchioles. • Right lung: no description • Left lung: no description • Bronchioles: primary bronchi divide into smaller and smaller airways which become the bronchioles. They continue to divide and get smaller until they end in the alveolus. • Alveoli: The sites where gas exchange occur. Make up the bulk of the lungs. This is where the O 2nters blood and CO le2ves blood to enter the air. The structure of the alveoli is such that the diffusion of the gas is maximized. This is accomplished by the very large SAfor diffusion and the short distances that gases have to diffuse. • Smooth muscle: no description • Alveolar space: no description • Capillary: no description Section 10.4 –Anatomy: Blood Vessels and Blood Flow • The pulmonary artery, which delivers deoxygenated blood to the lungs, branches extensively to form a dense network of capillaries around each alveolus. • The structure of the capillaries and blood flow characteristics maximize gas exchange. • These characteristics include thin endothelial walls, large total cross-sectional area, and a very low blood velocity. • Hence, in the capillaries, oxygen diffuses into the blood while carbon dioxide diffuses out. 2 • From the capillaries, the oxygen-rich blood flows back to the left side of the heart through the pulmonary vein. Section 10.5 –Anatomy: Histology Structure of an Alveolus • There are roughly 300 million alveoli in a healthy human lung, each with a diameter of roughly 0.3 mm (1/100 of an inch). • The walls of the alveoli are one cell thick and are composed of alveolar epithelial cells (type I cells). • Type II cells secrete a fluid called surfactant (which we will examine later) that lines the alveoli. • Large numbers of capillaries surround the alveoli in close proximity. • The region between the alveolar space and the capillary lumen is the respiratory membrane. • This membrane, which can have a thickness as narrow as 0.3 microns, is where gas exchange takes place between air and blood. • Cells of the immune system, including macrophages and lymphocytes, protect the body from airborne particles that make their way into the alveoli. • Fibers of elastin and collagen (not shown) are present in the walls of the alveoli, around blood vessel and bronchi. Section 10.6 – Pressures of the Lungs: Intrapleural Pressure • In order to understand inspiration (inhaling) and expiration (exhaling), we must understand the environment of the lungs. • There are two thin pleural membranes:  One lines and sticks to the ribs (the parietal pleura) while the other surrounds and sticks to the lungs (the viceral pleura).  These two layers of membrane form the intrapleural space, • Intrapleural Space:  Contains a very small amount of pleural fluid (roughly 10-15ml). • Pleural Fluid: 3  This fluid reduces friction between the two pleural membranes during breathing.  Due to their nature and attached muscle, the ribs tend to spring outward, while the lungs, due to the presence of elastin, tend to recoil and collapse. • Let's have a look at the pressures inside and outside the lungs. Section 10.7 – Pressures of the Lungs:Alveolar and Atmospheric Pressure • The pressure inside the lungs is called the alveolar pressure (or intrapulmonary pressure), and the pressure in the intrapleural space is called the intrapleural pressure. • The atmospheric pressure (outside the body):  760 mmHg at sea level.  Between breaths, the alveolar and atmospheric pressures are the same at 760 mmHg (0 difference), • The Intrapleural pressure:  In the intrapleural space it’s roughly 756 mmHg (a difference of 4 mmHg).  The chest wall and lungs moving in opposite directions cause this lower intrapleural pressure. Section 10.8 – Pressures of the Lungs: Transpulmonary Pressure • Transpulmonary pressure:  The difference between the alveolar and intrapleural pressures  Calculated using equation 1:  Transp. Pressure =Alveolar Pressure – Intrapleural Pressure • The transpulmonary pressure is important because this difference in pressure across the alveoli and intrapleural space holds the lungs open. • We can calculate the transpulmonary pressure using the values below and equation 1 above.  Transpulmonary Pressure = 760mmHg – 756mmHg = +4mmHg • In a healthy set of lungs, the transpulmonary pressure is positive (outward) and keeps the lungs and alveoli open. • Let's examine an unhealthy situation. Section 10.9 – Pressures of the Lungs: Pneumothorax • If both the alveolar and intrapleural pressures were equal, this would result in a transpulmonary pressure of 0 mmHg. Recall equation 1:  Transp. Pressure =Alveolar Pressure – Intrapleural Pressure • In this situation, there would be no pressure holding the lungs open and they would collapse, producing a pneumothorax: 4  This occurs when the intrapleural space is punctured, causing the alveolar pressure and intrapleural pressure to become equal (both are 760 mmHg).  Generally, only one lung collapses because the intrapleural space of each lung is isolated from the other. Section 10.10 – Ventilation: Boyle’s Law • Boyle’s Law:  Important for pulmonary ventilation  States that when the volume of a container decreases, the pressure inside increases (and vice versa – when the volume increases, the pressure decreases).  Therefore, pressure is said to vary inversely with volume and can be written as follows:  pressureα 1 volume Section 10.11 – Ventilation: Inspiration and Expiration • Just like moving blood through a vessel, moving air into the lungs requires a pressure gradient. • With the lungs, however, this gradient is an air pressure gradient. • Simply put, to move air into the lungs requires high pressure outside and low pressure in the alveoli. • To move air out requires high alveolar pressure and low atmospheric pressure. • Since you cannot increase the outside atmospheric pressure, the alveolar pressure must change. • Let's now explore how the body changes the alveolar pressure. 5 Section 10.11 – Ventilation: Mechanisms of Inspiration • To decrease the alveolar (intrapulmonary) pressure (according to Boyle's Law), the lung volume must increase. • To increase the volume, the diaphragm contracts, moving downward, and the external intercostal muscles of the rib contract, lifting the rib cage up and out. • Both these events cause the lung volume to increase, dropping the alveolar pressure inside to roughly 759 mmHg. • Apressure gradient now exists with the low pressure inside the lungs and higher pressure outside (760 mmHg). • As a result, air flows into the lungs. • The contraction of these respiratory muscles is an active process that relies on signals from the respiratory center in the brainstem (which we will see later) and causes the muscles to contract. 6 Section 10.13 – Ventilation: Mechanisms of Expiration • The mechanisms of expiration depend on whether you are resting or exercising. • At rest:  The diaphragm and external intercostal muscles simply relax, causing the lungs to recoil to their original size.  As a result, the volume decreases, causing the alveolar (intrapulmonary) pressure to increase above atmospheric pressure.  The pressure gradient is now reversed (high inside at 761 mmHg and low outside at 760 mmHg) and air flows out.  This is a passive process since no muscle contractions occur. • During Exercise:  Air must be forced out of the lungs.  This requires contraction of the abdominal muscles and the internal intercostal muscles of the ribs.  When these muscles contract, they further decrease the volume of the lungs, creating a larger pressure gradient (much higher on the inside at 763 mmHg than outside at 760 mmHg) and forcing the air out. Section 10.14 – Ventilation: Model of a Lung • Video of a bottle as a “lung:” Notice that as the "diaphragm" is pulled down, the volume increases, the pressure decreases, air rushes in, and the "lungs" inflate. When the diaphragm relaxes, the volume decreases, the pressure increases, air flows out, and the "lungs" deflate. 7 Section 10.15 – Ventilation: Make Your Own Lung • Make your own lung – step by step. Section 10.16 – Pulmonary Compliance • Pulmonary compliance:  The stretchability of the lungs  The more stretchable, the more compliant.  Pulmonary compliance is defined as the volume change that occurs as a result of a change in pressure, as shown in equation 3: VolumeChange  Compliance= PressureChange Section 10.17 – Pulmonary Compliance (cont’d) • Pulmonary compliance is important because it determines the ease of breathing. • Alung that has decreased compliance (decreased stretchability) is difficult to inflate while one that has high compliance is easy to inflate but can be difficult to deflate. Consider the examples at right. • There are two major factors that influence the compliance (or elastic behavior) of the lung: 1. The amount of elastic tissue that is found in walls of the alveoli, blood vessels, and bronchi 2. The surface tension of the film of liquid that is lining all the alveoli • Both of these factors decrease compliance by tending to collapse the lungs, making breathing difficult. Let's have a closer look at each one. 8 Section 10.18 - Pulmonary Compliance: Elastic Tissue Components • Fibers of elastin and collagen are present in the walls of the alveoli, blood vessels, and bronchioles. • These fibers are arranged in a special geometric arrangement where the elastin fibers are easily stretched but collagen fibers are not. • The arrangement of these fibers contributes to about one-third of the total compliance or "elastic behavior" of a healthy lung. • The more elastin, the less compliant the lungs – much like a very thick rubber band is not very stretchable while a very thin rubber band is. Section 10.19 - Pulmonary Compliance: Surface Tension • The remaining two-thirds of the elastic behavior of the lung can be attributed to the surface tension of the liquid film lining the alveoli. • The surface tension from this thin film tends to collapse the alveoli, decreasing compliance and making inflation difficult. • Surface tension:  The force developed at the surface of a liquid and is due to the attractive forces between water molecules. • The animation at right shows that the majority of forces between water molecules in a drop of water are inward. • This is because there is no outward balancing force at the surface of the water. 9 • Therefore, the overall effect is to pull the water molecules into a tight ball. • In the lungs, this attraction between water molecules will cause the fluid-lined alveoli to collapse. • How do you keep your lungs from collapsing due to this surface tension? Let's have a look. Section 10.20 - Pulmonary Compliance: Pulmonary Surfactant • Pulmonary surfactant:  Alipoprotein substance produced by type II (or great) alveolar cells and consists mostly of phospholipids  Therefore, the surfactant molecule has a hydrophilic head that faces the water and a hydrophobic tail that faces away.  When surfactant is added to water, it lies on the surface at the air-water interface.  The phospholipid head groups will be attracted to the water molecules and will balance the inward forces with an outward one.  The forces will now be equal in every direction and the water drop will flatten out due to the decreased surface tension. Section 10.21 - Pulmonary Compliance: Pulmonary Surfactant and Infant Respiratory Distress Syndrome • Premature babies born before 36 weeks gestation do not produce proper amounts of surfactant. • Since these babies do not have enough surfactant, their alveoli tend to collapse, making it very difficult to inhale and causing infant respiratory distress syndrome. • These babies expend incredible amounts of energy inflating their lungs and can die from exhaustion. • In order to avoid this, premature babies receive a dose of surfactant directly into the lungs at birth, which will enable them to breathe easier. 10 Section 10.22 – Lung Volumes • The maximum amount of air our lungs can hold is roughly 5 liters. • This does not mean that we breathe in 5 liters of air on every breath. • The amount of air we inhale/exhale depends on a variety of factors, including our health, age, and level of activity. • In this section, we will examine the lung volumes and the apparatus used to measure them. Section 10.23 – Spirometer • Spirometer:  Adevice used to measure lung volumes and capacities.  Spirometers are also useful in helping diagnose pulmonary diseases like asthma, bronchitis, and emphysema. • Although spirometers now are quite modern and are likely attached to computers, the one below is still in use today. • This spirometer consists of an air-filled chamber with an attached hose. • As air is drawn out of the chamber during inhalation, the chamber falls and pulls on a chain attached to a pen that rises. • During exhalation, the chamber fills, rises, and the pen falls. • As the pen goes up and down, it marks a path on a calibrated piece of paper that indicates the lung volumes. 11 Section 10.24 - Lung Volumes and Lung Capacities • There are four basic lung volumes and four lung capacities. • Alung capacity consists of two or more lung volumes. • Lung Volumes:  Tidal volume (VT):  The volume of air entering (inspiration) or leaving (expiration) the lungs during one breath at rest = (500 ml)  Varies on person’s size or level of activity  During exercising, VT increases because taking deeper breaths.  Inspiratory reserve volume (IRV):  The maximum amount of air that can enter the lungs in addition to the tidal volume (2500 ml) – extra air inhaling above VT  This is the amount of room in the lung that is on reserve  Expiratory reserve volume (ERV):  The maximum amount of air that can be exhaled beyond the tidal volume (1000 ml/1 L) - the amount of air you exhale down to the residual volume  Residual volume (RV):  The remaining air in the lungs after a maximal expiration (1200 ml) - the amount of air that is always in the lungs no matter how hard you exhale • Lung Capacities:  Inspiratory capacity (IC):  The maximum amount of air that can be inhaled after exhaling the tidal volume (IC = tidal volume + inspiratory reserve volume)  Functional residual capacity (FRC):  The amount of air still in the lungs after exhalation of the tidal volume (FRC = expiratory reserve volume + residual volume)  Vital capacity (VC):  The maximum amount of air that can be exhaled after a maximal inhalation (VC = inspiratory reserve volume + tidal volume + expiratory reserve volume) - max air that can be moved voluntarily in or out of the lungs in a single breath  4000ml  Total lung capacity:  The maximum amount of air that lungs can hold (equal to vital capacity + residual volume)  ~5L Section 10.25 - Pulmonary Ventilation: Calculate 12 • Pulmonary Ventilation:  also called minute ventilation  The amount of air that enters all of the conducting and respiratory zones in one minute. • The conducting zone:  Also referred to as the anatomical dead space  The area of the lungs where no gas exchange takes place (because there are no alveoli). • The respiratory zone:  The region of the lungs where alveoli are located. Section 10.26 - Pulmonary Ventilation: Calculate (cont’d) • Pulmonary ventilation is important to understand because it will determine the amount of air and hence the amount of oxygen that is available to the body. • Pulmonary ventilation (VE) can be determined by equation 4.  breaths/min¿ VE=tidalvolume ml xrespiratoryrate¿ • At rest, the pulmonary ventilation is roughly 7500 ml/min. • This is the amount of air that is entering the entire pulmonary system – conducting and respiratory zones. • However, not all of this air is available for gas exchange; only the air in the respiratory zones (in the alveoli) will be involved. • This volume is called the alveolar ventilation, which we will discuss on the following page. Section 10.27 -Alveolar Ventilation: Calculate • Alveolar ventilation (VA): 13  The volume of air entering only the respiratory zone each minute.  It represents the volume of fresh air available for gas exchange.  While pulmonary ventilation (VE) is easily measured (tidal volume x breaths per min), alveolar ventilation is difficult because the anatomical dead space volume must be taken into account.  If this dead space volume is known, alveolar ventilation can be determined.  Let's have a look at how this is achieved. Section 10.28 -Alveolar Ventilation: Calculate (cont’d) • If a tidal volume of 500 ml is inhaled, approximately 150 ml remains in the conducting zone where there are no alveoli; this is the anatomical dead space volume. • The remaining 350 ml (500 – 150 ml) reaches the alveolar compartments and participates in gas exchange. • The volume of the anatomical dead space, although difficult to determine, can be estimated. • As a rule of thumb, the dead space volume in ml for a normal healthy subject is approximately equal to the person's body weight in pounds (for example, if body weight is 100 pounds, dead space volume is 100 ml). • With this in mind, alveolar ventilation (VA) can be calculated using the equation at right. • The dead space ventilation (VD) is also a rate and takes into account not only the volume of the dead space but the respiratory rate as well. • Let’s try an example. 14 Section 10.29 -Alveolar Ventilation: Example • Look at the example below that shows how to calculate alveolar ventilation, and then try the checkpoint below. • You should now have a good understanding of the pressures in and around the lungs and how they, in conjunction with Boyle's law, produce inspiration and expiration. • Now that air is in the lungs, it is time to examine the movement of oxygen and carbon dioxide into and out of the blood. • Before we do this, we must first discuss the topic of partial pressure of gases. Section 10.30 - Partial Pressure of Gases • The partial pressure of a gas is the pressure exerted by that one gas in a mixture of gases. • For example, air at sea level consists of a mixture of 21% oxygen, 78% nitrogen, (and other inert gases) and 0.03% carbon dioxide. • This mixture of gases exerts a pressure of 760 mmHg at sea level. • Each one of these gases partially contributes to the 760 mmHg air pressure. 15 • The following page explains how to calculate the partial pressures of oxygen and carbon dioxide. Section 10.31 - Partial Pressure of Gases (cont’d) • In order to calculate the partial pressure of a gas in air, we use the equation at right. • Example: The partial pressure of O 2PO ) 2n air at sea level: PO =2760 x (20.93 / 100) PO =2159 mmHg • This can be done for carbon dioxide as well, giving a PCO2 of 0.3 mmHg. (Please note that these numbers can vary slightly.) Section 10.32 - Partial Pressure of Gases (cont’d) • The previous numbers given for the partial pressure of gases inside the lungs represent mathematical estimates and would be correct if we assume gas exchange was not taking place. • Once the air enters the lungs, however, oxygen is immediately taken up into the blood and carbon dioxide is given off into the lungs. • Because of the mixing of the "new inhaled" air with the "old" gas being removed, the actual value for alveolar PO2is lower and the PCO2 is much higher. • The approximate real values for alveolar P O2 and PCO2 are shown below. These are the true values after gas exchange has taken place (and may vary slightly).  P = 105 mmHg O2  P CO2 = 40 mmHg Section 10.33 - Partial Pressures: Their Importance • Just like the movement of blood through vessels and the movement of air into and out of the lungs, oxygen and carbon dioxide move down a pressure gradient. • In this case, the gradient is a partial pressure gradient. • Consequently, oxygen and carbon dioxide will move from areas of high partial pressure to low partial pressure. 16 • Oxygen and carbon dioxide can dissolve in water.  As a result, partial pressure can also be used to describe the amount of oxygen or carbon dioxide dissolved in the plasma. • With this in mind, let's look at the movement of these two gases. Section 10.34 - Partial Pressures of Gases across theAlveoli: Diffusion • As shown in the animation at right, blood entering the lungs has a partial pressure of oxygen (PO ) 2f 40 mmHg and a partial pressure of carbon dioxide (PCO ) of 2 46 mmHg; alveoli, on the other hand, have a PO of 102 mmHg and a PCO of 40 2 mmHg. • As the blood moves past the alveoli, oxygen and carbon dioxide will diffuse down their respective partial pressure gradients. • Oxygen will move from the alveolar space (PO of 102 mmHg) to the blood stream (PO o2 40 mmHg)  Therefore, O2 will move down its partial pressure gradient from the alveoli and into the blood, as the blood moves through the lungs. • Carbon dioxide will move from the blood (PCO of 46 2mHg) to the alveolar space (PCO of240 mmHg)  Therefore, CO diff2ses down its partial pressure gradient from the blood and into the alveoli as the blood moves through the lungs. • As the blood leaves the alveolus, the PO an2 PCO will 2ave essentially equilibrated with the alveolar air. • Once the blood has the left lungs, the partial pressure of oxygen in the blood will increase to 100 mmHg, and the partial pressure of CO will 2rop to 40 mmHg Section 10.35 - Partial Pressures: O and2CO throug2out the Circulatory System • The events in the animation at right are summarized as follows: 1. Blood leaving the lungs has a high PO (1002mmHg) and low PCO (40 2 mmHg). 2. Blood returns to the left side of the heart and is pumped to the systemic circulation. 3. Blood enters tissue beds with the same PO (1002mmHg) and PCO (40 2 mmHg). 4. Cells have a low PO (402mmHg) and high PCO (46 mmHg) 2nside. 5. As blood flows through capillaries, oxygen diffuses into the cells and carbon dioxide diffuses out down their respective partial pressure gradients. 6. Blood leaving the tissue will have equilibrated with cells; it will have a PO 2f 40 mmHg and PCO of 46 m2Hg. 7. Blood returns to the right side of the heart to be pumped to the lungs, and the process repeats. Section 10.36 - Partial Pressures: Some Important Points 17 • Summarized below are all the partial pressures throughout the systemic circulation. • It is extremely important to remember that the partial pressure of oxygen or carbon dioxide in the blood refers to the amount of these gases dissolved in the plasma. • As we will see, however, this is not the only way that the oxygen and carbon dioxide are transported in the blood. • In fact, there is very little oxygen dissolved in the plasma – not nearly enough to keep us alive. • That is why there are other mechanisms to maximize the delivery of oxygen to the tissues and to remove carbon dioxide from the cells. • We will now look at these other more efficient mechanisms of delivery. Section 10.37 – Oxygen Transport • As we have already seen, oxygen is carried in the blood dissolved in the plasma, and it is carried in red blood cells (RBCs) attached to a protein called hemoglobin. • Hemoglobin can carry much more oxygen. • Let's examine and compare these two methods in more detail. 18 Section 10.38 - Oxygen Transport: Dissolved in Plasma • Very little oxygen is transported in the blood dissolved in plasma. • As indicated at right, transporting oxygen throughout the body dissolved in plasma cannot supply enough oxygen to meet the body's needs. • This way of transporting oxygen is obviously very inadequate and makes up only 1.5% of the total oxygen transported in the blood. • The other 98.5% of the oxygen is carried attached to a special protein found inside red blood cells. • Let's examine this transport mechanism now. Section 10.39 - Oxygen Transport: Red Blood Cells and Hemoglobin • Most of the oxygen (98.5%) is carried in red blood cells (RBCs) attached to a large molecule called hemoglobin (Hb). • Each molecule of hemoglobin can carry 4 oxygen molecules, as shown at right. • To better understand how hemoglobin performs this function, let’s have a closer look at the structure and production of red blood cells and hemoglobin. Section 10.40 - Oxygen Transport: Red Blood Cells • Red blood cells (RBCs):  Also called erythrocytes 19  Doughnut-shaped cells without the hole (as shown at right).  These cells are just large enough to squeeze through the smallest of capillaries single file.  They are one of the few cells in the body that don’t contain a nucleus in their mature, circulating form.  However, during the early stag
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