Pulmonary System Physiology PDF

01 Pulmonary Ventilation Assoc. Prof. Dr. Turan Onur BAYAZIT School of Medicine Physiology & Biophysics Department : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • The main functions of respiration are to provide...

01 Pulmonary Ventilation Assoc. Prof. Dr. Turan Onur BAYAZIT School of Medicine Physiology & Biophysics Department : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • The main functions of respiration are to provide oxygen to the tissues and remove carbon dioxide. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • The four major components of respiration are the following: • 1) pulmonary ventilation, which means the inflow and outflow of air between the atmosphere and the lung alveoli; • 2) diffusion of oxygen (O2) and carbon dioxide (CO2) between the alveoli and the blood; • 3) transport of oxygen and carbon dioxide in the blood and body fluids to and from the body’s tissue cells; • 4) regulation of ventilation and other facets of respiration. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Mechanics of pulmonary ventilation Muscles that cause lung expansion and contraction • The lungs can be expanded and contracted in two ways: • 1) by downward or upward movement of the diaphragm to lengthen or shorten the chest cavity; : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Mechanics of pulmonary ventilation Muscles that cause lung expansion and contraction • The lungs can be expanded and contracted in two ways: • 2) by elevation or depression of the ribs to increase or decrease the anteroposterior diameter of the chest cavity. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Mechanics of pulmonary ventilation Muscles that cause lung expansion and contraction • Normal quiet breathing is accomplished almost entirely by movement of the diaphragm. • During inspiration, contraction of the diaphragm pulls the lower surfaces of the lungs downward. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Surfactant, Surface Tension, and Collapse of the Alveoli Surfactant and Its Effect on Surface Tension • Surfactant is a surface-active agent in water, which means that it greatly reduces the surface tension of water. • It is secreted by special surfactant-secreting epithelial cells called type II alveolar epithelial cells, which constitute about 10% of the surface area of the alveoli. • These cells are granular, containing lipid inclusions that are secreted in the surfactant into the alveoli. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Surfactant, Surface Tension, and Collapse of the Alveoli Surfactant and Its Effect on Surface Tension • Deficiency of lung surfactant in premature newborns causes respiratory distress syndrome (RDS), a leading cause of perinatal mortality. • Supplementing exogenous surfactants extracted from animals' lung to preemies suffering from RDS has completely altered neonatal care in industrialized countries. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Surfactant, Surface Tension, and Collapse of the Alveoli Surfactant and Its Effect on Surface Tension • Surfactant therapy has also been applied to the acute respiratory distress syndrome (ARDS) but to date with only limited success, which might be in part due to surfactant inhibition. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Recording changes in pulmonary volume— Spirometry • Pulmonary ventilation can be studied by recording the volume movement of air into and out of the lungs, a method called spirometry. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Recording changes in pulmonary volume—Spirometry • A typical basic spirometer consists of a drum inverted over a chamber of water, with the drum counterbalanced by a weight. • In the drum is a breathing gas, usually air or oxygen; a tube connects the mouth with the gas chamber. • When the person breathes into and out of the chamber, the drum rises and falls, and an appropriate recording is made. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Recording changes in pulmonary volume— Spirometry • A spirogram indicating changes in lung volume under different conditions of breathing. • For ease in describing the events of pulmonary ventilation, the air in the lungs has been subdivided in this diagram into four volumes and four capacities, which are the averages for a young adult man. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Volumes • 1. The tidal volume is the volume of air inspired or expired with each normal breath; it amounts to about 500 ml in the average healthy man.: https://orcid.org/0000-0002-7761-2617 : [email protected] : O-1137-2015 : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Volumes • 2. The inspiratory reserve volume is the extra volume of air that can be inspired over and above the normal tidal volume when the person inspires with full force; it is usually equal to about 3000 ml. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Volumes • 3. The expiratory reserve volume is the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration; this volume normally amounts to about 1100 ml in men. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Volumes • 4. The residual volume is the volume of air remaining in the lungs after the most forceful expiration; this volume averages about 1200 ml. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Capacities • In describing events in the pulmonary cycle, it is sometimes useful to consider two or more of the volumes together. • Such combinations are called pulmonary capacities. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Capacities • 1. The inspiratory capacity equals the tidal volume plus the inspiratory reserve volume. • This capacity is the amount of air ( ≈3500 ml) that a person can breathe in, beginning at the normal expiratory level and distending the lungs to the maximum amount. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Capacities • 2. The functional residual capacity equals the expiratory reserve volume plus the residual volume. • This capacity is the amount of air that remains in the lungs at the end of normal expiration (≈2300 ml). : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Capacities • 3. The vital capacity equals the inspiratory reserve volume plus the tidal volume plus the expiratory reserve volume. • This capacity is the maximum amount of air a person can expel from the lungs after first filling the lungs to their maximum extent and then expiring to the maximum extent (≈4600 ml). : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary volumes and capacities Pulmonary Capacities • 4. The total lung capacity is the maximum volume to which the lungs can be expanded with the greatest possible effort ( ≈5800 ml); it is equal to the vital capacity plus the residual volume. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 < Pulmonary volumes and capacities Pulmonary Capacities • Most pulmonary volumes and capacities are usually about 20% to 30% less in women than in men, and they are greater in large and athletic people than in small and asthenic people. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Minute respiratory volume equals respiratory rate times tidal volume • The minute respiratory volume is the total amount of new air moved into the respiratory passages each minute and is equal to the tidal volume times the respiratory rate per minute. • The normal tidal volume is about 500 ml, and the normal respiratory rate is about 12 breaths/min. • Therefore, the minute respiratory volume averages about 6 L/min. • A person can live for a short period with a minute respiratory volume as low as 1.5 L/min and a respiratory rate of only 2 to 4 breaths/min. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Alveolar ventilation • The ultimate importance of pulmonary ventilation is to renew the air in the gas exchange areas of the lungs continually, where air is in proximity to the pulmonary blood. • These areas include the alveoli, alveolar sacs, alveolar ducts, and respiratory bronchioles. • The rate at which new air reaches these areas is called alveolar ventilation. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Dead space and its effect on alveolar ventilation • Some of the air a person breathes never reaches the gas exchange areas but simply fills respiratory passages, such as the nose, pharynx, and trachea, where gas exchange does not occur. • This air is called dead space air because it is not useful for gas exchange. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Normal Dead Space Volume • The normal dead space air in a young man is about 150 ml. • Dead space air increases slightly with age. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Anatomical Versus Physiological Dead Space • On occasion, some of the alveoli are nonfunctional or only partially functional because of absent or poor blood flow through the adjacent pulmonary capillaries. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Anatomical Versus Physiological Dead Space • Therefore, these alveoli must also be considered dead space. • When the alveolar dead space is included in the total measurement of dead space, this is called the physiological dead space, in contradistinction to the anatomical dead space. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Anatomical Versus Physiological Dead Space • In a person with healthy lungs, the anatomical and physiological dead spaces are nearly equal because all alveoli are functional in the normal lung but, in a person with partially functional or nonfunctional alveoli in some parts of the lungs, the physiological dead space may be as much as 10 times the volume of the anatomical dead space, or 1 to 2 liters. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Rate of alveolar ventilation • Alveolar ventilation per minute is the total volume of new air entering the alveoli and adjacent gas exchange areas each minute. • It is equal to the respiratory rate times the amount of new air that enters these areas with each breath: • where VA is the volume of alveolar ventilation per minute, Freq is the frequency of respiration per minute, VT is the tidal volume, and VD is the physiological dead space volume. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Trachea, Bronchi, and Bronchioles • The air is distributed to the lungs by way of the trachea, bronchi, and bronchioles. • One of the most important challenges in the respiratory passageways is to keep them open and allow easy passage of air to and from the alveoli. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Trachea, Bronchi, and Bronchioles • The bronchioles are not prevented from collapsing by the rigidity of their walls. • Instead, they are kept expanded mainly by the same transpulmonary pressures that expand the alveoli. • That is, as the alveoli enlarge, the bronchioles also enlarge, but not as much. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Muscular Wall of the Bronchi and Bronchioles • In all areas of the trachea and bronchi not occupied by cartilage plates, the walls are composed mainly of smooth muscle. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Resistance to Airflow in the Bronchial Tree • The greatest amount of resistance to airflow occurs not in the tiny air passages of the terminal bronchioles but in some of the larger bronchioles and bronchi near the trachea. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Resistance to Airflow in the Bronchial Tree • The reason for this high resistance is that there are relatively few of these larger bronchi in comparison with the approximately 65,000 parallel terminal bronchioles, through each of which only a minute amount of air must pass. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Resistance to Airflow in the Bronchial Tree • In some disease conditions, the smaller bronchioles play a far greater role in determining airflow resistance because of their small size and because they are easily occluded by the following: • • • 1) muscle contraction in their walls; 2) edema in the walls; 3) mucus collecting in the lumens of the bronchioles. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Nervous and Local Control of the Bronchiolar Musculature—Sympathetic Dilation of the Bronchioles • Direct control of the bronchioles by sympathetic nerve fibers is relatively weak because few of these fibers penetrate to the central portions of the lung. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Parasympathetic Constriction of the Bronchioles • These nerves secrete acetylcholine and, when activated, cause mild to moderate constriction of the bronchioles. • When a disease process such as asthma has already caused some bronchiolar constriction, superimposed parasympathetic nervous stimulation often worsens the condition. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Parasympathetic Constriction of the Bronchioles • When this situation occurs, administration of drugs that block the effects of acetylcholine, such as atropine, can sometimes relax the respiratory passages enough to relieve the obstruction. • Sometimes the parasympathetic nerves are also activated by reflexes that originate in the lungs. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Parasympathetic Constriction of the Bronchioles • Most of these reflexes begin with irritation of the epithelial membrane of the respiratory passageways, initiated by noxious gases, dust, cigarette smoke, or bronchial infection. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Local Secretory Factors May Cause Bronchiolar Constriction • Several substances formed in the lungs are often active in causing bronchiolar constriction. • Two of the most important of these are histamine and slow reactive substance of anaphylaxis. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Local Secretory Factors May Cause Bronchiolar Constriction • The same irritants that cause parasympathetic constrictor reflexes of the airways—smoke, dust, sulfur dioxide, and some of the acidic elements in smog—may also act directly on the lung tissues to initiate local, non-nervous reactions that cause obstructive constriction of the airways. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Local Mucus Lining the Respiratory Passageways and Cilia Action to Clear the Passageways • All the respiratory passages, from the nose to the terminal bronchioles, are kept moist by a layer of mucus that coats the entire surface. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Local Mucus Lining the Respiratory Passageways and Cilia Action to Clear the Passageways • These cilia beat continually at a rate of 10 to 20 times/sec and the direction of their “power stroke” is always toward the pharynx. • That is, the cilia in the lungs beat upward, whereas those in the nose beat downward. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Cough Reflex • The bronchi and trachea are so sensitive to light touch that slight amounts of foreign matter or other causes of irritation initiate the cough reflex. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Sneeze Reflex • The sneeze reflex is very much like the cough reflex, except that it applies to the nasal passageways instead of the lower respiratory passages. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Normal Respiratory Functions of the Nose • As air passes through the nose, three distinct normal respiratory functions are performed by the nasal cavities: • 1) the air is warmed by the extensive surfaces of the conchae and septum, a total area of about 160 square centimeters; : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Normal Respiratory Functions of the Nose • These functions together are called the air-conditioning function of the upper respiratory passageways. • Ordinarily, the temperature of the inspired air rises to within 1°C of body temperature and to within 2% to 3% of full saturation with water vapor before it reaches the trachea. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Filtration Function of the Nose • The hairs at the entrance to the nostrils are important for filtering out large particles. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Functions of Respiratory Passageways Size of Particles Entrapped in Respiratory Passages the • Many of the particles that become entrapped in the alveoli are removed by alveolar macrophages and others are carried away by the lung lymphatics. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • The lung has two circulations, a high-pressure, low-flow circulation • and a low-pressure, high-flow circulation. • The high-pressure, low-flow circulation supplies systemic arterial blood to the trachea, bronchial tree (including the terminal bronchioles), supporting tissues of the lung, and outer coats (adventitia) of the pulmonary arteries and veins. • The bronchial arteries, which are branches of the thoracic aorta, supply most of this systemic arterial blood at a pressure that is only slightly lower than the aortic pressure. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • The low-pressure, high-flow circulation supplies venous blood from all parts of the body to the alveolar capillaries where oxygen (O2) is added and carbon dioxide (CO2) is removed. • The pulmonary artery, which receives blood from the right ventricle, and its arterial branches carry blood to the alveolar capillaries for gas exchange, and the pulmonary veins then return the blood to the left atrium to be pumped by the left ventricle though the systemic circulation. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Physiological anatomy of the pulmonary circulatory system Lymphatics • Lymph vessels are present in all the supportive tissues of the lung, • beginning in the connective tissue spaces that surround the terminal bronchioles, coursing to the hilum of the lung, and then mainly into the right thoracic lymph duct. • Particulate matter entering the alveoli is partly removed by these lymph vessels, and plasma protein leaking from the lung capillaries is also removed from the lung tissues, thereby helping to prevent pulmonary edema. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Blood volume of the lungs • The blood volume of the lungs is about 450 ml, about 9% of the total blood volume of the entire circulatory system. • Approximately 70 ml of this pulmonary blood volume is in the pulmonary capillaries; • the remainder is divided about equally between the pulmonary arteries and veins ( 380 / 2 = 190 ml ). : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Blood volume of the lungs Lungs Serve as a Blood Reservoir • Under various physiological and pathological conditions, the quantity of blood in the lungs can vary from as little as half-normal up to twice normal. • For example, when a person blows out air so hard that high pressure is built up in the lungs, such as when blowing a trumpet, as much as 250 ml of blood can be expelled from the pulmonary circulatory system into the systemic circulation. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Blood volume of the lungs Lungs Serve as a Blood Reservoir • Also, loss of blood from the systemic circulation by hemorrhage can be partly compensated for by the automatic shift of blood from the lungs into the systemic vessels. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Blood flow through the lungs and its distribution • Blood flow through the lungs is essentially equal to the cardiac output. • Therefore, the factors that control cardiac output—mainly peripheral factors also control pulmonary blood flow. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Blood flow through the lungs and its distribution • Under most conditions, the pulmonary vessels act as distensible tubes that enlarge with increasing pressure and narrow with decreasing pressure. • For adequate aeration of the blood to occur, the blood must be distributed to the segments of the lungs where the alveoli are best oxygenated. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Decreased Alveolar Oxygen Reduces Local Alveolar Blood Flow and Regulates Pulmonary Blood Flow Distribution • Low O2 concentration may have the following effects: • 1) stimulate release of, or increase sensitivity to, vasoconstrictor substances such as endothelin or reactive oxygen species; • 2) decrease release of a vasodilator, such as nitric oxide, from the lung tissue. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Effect of hydrostatic pressure gradients in the lungs on regional pulmonary blood flow • Note that in the standing position at rest, there is little flow in the top of the lung but about five times as much flow in the bottom. • To help explain these differences, the lung is often described as being divided into three zones. • In each zone, the patterns of blood flow are quite different. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Zones 1, 2, and 3 of Pulmonary Blood Flow • Normally, the lungs have only zones 2 and 3 blood flow—zone 2 (intermittent flow) in the apices and zone 3 (continuous flow) in all the lower areas. • For example, when a person is in the upright position, the pulmonary arterial pressure at the lung apex is about 15 mm Hg less than the pressure at the level of the heart. • Therefore, the apical systolic pressure is only 10 mm Hg (25 mm Hg at heart level minus 15 mm Hg hydrostatic pressure difference). : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary Edema • The most common causes of pulmonary edema are • 1. Left-sided heart failure or mitral valve disease, with consequent great increases in pulmonary venous pressure and pulmonary capillary pressure and flooding of the interstitial spaces and alveoli . : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pulmonary Edema • The most common causes of pulmonary edema are • 2. Damage to the pulmonary blood capillary membranes caused by infections such as pneumonia or by breathing noxious substances such as chlorine gas or sulfur dioxide gas • Each of these mechanisms causes rapid leakage of plasma proteins and fluid out of the capillaries and into the lung interstitial spaces and alveoli. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pleural Effusion—Collection of Large Amounts of Free Fluid in the Pleural Space • Pleural effusion is analogous to edema fluid in the tissues and can be called edema of the pleural cavity. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pleural Effusion—Collection of Large Amounts of Free Fluid in the Pleural Space • The causes of the effusion are the same as the causes of edema in other tissues including the following: • 1) blockage of lymphatic drainage from the pleural cavity; • 2) cardiac failure, which causes excessively high peripheral and pulmonary capillary pressures, leading to excessive transudation of fluid into the pleural cavity; : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pleural Effusion—Collection of Large Amounts of Free Fluid in the Pleural Space • The causes of the effusion are the same as the causes of edema in other tissues including the following: • 3) greatly reduced plasma colloid osmotic pressure, thus allowing excessive transudation of fluid; • 4) infection or any other cause of inflammation of the surfaces of the pleural cavity, which increases permeability of the capillary membranes and allows rapid dumping of plasma proteins and fluid into the cavity. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Introduction • After the alveoli are ventilated with fresh air, the next step in respiration is diffusion of oxygen (O2) from the alveoli into the pulmonary blood and diffusion of carbon dioxide (CO2) in the opposite direction, out of the blood into the alveoli. • The process of diffusion is simply the random motion of molecules in all directions through the respiratory membrane and adjacent fluids. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Gas Pressures in a Mixture of Gases—Partial Pressures of Individual Gases • In respiratory physiology, one deals with mixtures of gases, mainly oxygen, nitrogen, and carbon dioxide. • The rate of diffusion of each of these gases is directly proportional to the pressure caused by that gas alone, which is called the partial pressure of that gas. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Gas Pressures in a Mixture of Gases Partial Pressures of Individual Gases • The air has an approximate composition of 78% nitrogen and 21% oxygen. • The total pressure of this mixture at sea level averages 760 mm Hg. • The partial pressure of nitrogen in the mixture is 600 mm Hg, and the partial pressure of O2 is 160 mm Hg; the total pressure is 760 mm Hg, the sum of the individual partial pressures. • The partial pressures of individual gases in a mixture are designated by the symbols PO2, PCo2, PN2, PHe, and so forth. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Pressures of Gases Dissolved in Water and Tissues • Gases dissolved in water or in body tissues also exert pressure because the dissolved gas molecules are moving randomly and have kinetic energy. • Furthermore, when the gas dissolved in fluid encounters a surface, such as the membrane of a cell, it exerts its own partial pressure in the same way as a gas in the gas phase. • The partial pressures of the separate dissolved gases are designated the same as the partial pressures in the gas state—that is, PO2, PCo2, PN2, PHe, and so forth. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Factors That Determine Partial Pressure of a Gas Dissolved in a Fluid • The partial pressure of a gas in a solution is determined not only by its concentration but also by the solubility coefficient of the gas. • That is, some types of molecules, especially CO2, are physically or chemically attracted to water molecules, whereas other types of molecules are repelled. • When molecules are attracted, far more of them can be dissolved without building up excess partial pressure within the solution. • Conversely, in the case of molecules that are repelled, high partial pressure will develop with fewer dissolved molecules. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Factors That Determine Partial Pressure of a Gas Dissolved in a Fluid • These relationships are expressed by the following formula, which is Henry’s law: • When partial pressure is expressed in atmospheres (1 atmosphere [1 atm] pressure equals 760 mm Hg) and concentration is expressed in volume of gas dissolved in each volume of water. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Diffusion of Gases Between Gas Phase in Alveoli and Dissolved Phase in Pulmonary Blood • The partial pressure of each gas in the alveolar respiratory gas mixture tends to force molecules of that gas into solution in the blood of the alveolar capillaries. • Conversely, the molecules of the same gas that are already dissolved in the blood are bouncing randomly in the fluid of the blood, and some of these bouncing molecules escape back into the alveoli. • The rate at which they escape is directly proportional to their partial pressure in the blood. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 COMPOSITIONS OF ALVEOLAR AIR AND ATMOSPHERIC AIR ARE DIFFERENT Alveolar Air Is Slowly Renewed by Atmospheric Air : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 DIFFUSION OF GASES THROUGH THE RESPIRATORY MEMBRANE Respiratory Unit • The respiratory unit is also called respiratory lobule, which is composed of a respiratory bronchiole, alveolar ducts, atria, and alveoli. • There are about 300 million alveoli in the two lungs, and each alveolus has an average diameter of about 0.2 millimeter. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 DIFFUSION OF GASES THROUGH THE RESPIRATORY MEMBRANE Respiratory Unit • The alveolar walls are extremely thin, and between the alveoli is an almost solid network of interconnecting capillaries. • Because of the extensiveness of the capillary plexus, the flow of blood in the alveolar wall has been described as a sheet of flowing blood. • The alveolar gases are in very close proximity to the blood of the pulmonary capillaries. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 DIFFUSION OF GASES THROUGH THE RESPIRATORY MEMBRANE Respiratory Unit • Furthermore, gas exchange between the alveolar air and pulmonary blood occurs through the membranes of all the terminal portions of the lungs, not merely in the alveoli. • All these membranes are collectively known as the respiratory membrane, also called the pulmonary membrane. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 DIFFUSION OF GASES THROUGH THE RESPIRATORY MEMBRANE Respiratory Membrane • the ultrastructure of the respiratory membrane; • the diffusuion of O2 from the alveolus into the red blood cell and diffusion of CO2 in the opposite direction. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 DIFFUSION OF GASES THROUGH THE RESPIRATORY MEMBRANE Respiratory Membrane • The average diameter of the pulmonary capillaries is only about 5 micrometers, which means that red blood cells must squeeze through them. • The red blood cell membrane usually touches the capillary wall, so O2 and CO2 need not pass through significant amounts of plasma as they diffuse between the alveolus and red blood cell. • This, too, increases the rapidity of diffusion. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 RESPIRATORY CENTER • The respiratory center is composed of several groups of neurons located bilaterally in the medulla oblongata and pons of the brain stem. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 RESPIRATORY CENTER • It is divided into three major collections of neurons: • 1) a dorsal respiratory group, located in the dorsal portion of the medulla, which mainly causes inspiration; • 2) a ventral respiratory group, located in the ventrolateral part of the medulla, which mainly causes expiration; • 3) the pneumotaxic center, located dorsally in the superior portion of the pons, which mainly controls rate and depth of breathing . : [email protected] : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : +90 505 434 40 89 brain_ist 01 Inspiratory “Ramp” Signal • The nervous signal that is transmitted to the inspiratory muscles, mainly the diaphragm, is not an instantaneous burst of action potentials. • Instead, it begins weakly and increases steadily in a ramp manner for about 2 seconds in normal respiration. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 Inspiratory “Ramp” Signal • It then ceases abruptly for approximately the next 3 seconds, • which turns off the excitation of the diaphragm • and allows elastic recoil of the lungs and chest wall to cause expiration. : [email protected] : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : +90 505 434 40 89 brain_ist 01 PNEUMOTAXIC CENTER LIMITS DURATION OF INSPIRATION AND INCREASES RESPIRATORY RATE • The function of the pneumotaxic center is primarily to limit inspiration, • which has a secondary effect of increasing the rate of breathing • because limitation of inspiration also shortens expiration and the entire period of each respiration. • A strong pneumotaxic signal can increase the rate of breathing to 30 to 40 breaths/min, • whereas a weak pneumotaxic signal may reduce the rate to only 3 to 5 : [email protected] : +90 505 434 40 89 brain_ist : breaths/min. O-1137-2015 : https://orcid.org/0000-0002-7761-2617 01 LUNG INFLATION SIGNALS LIMIT INSPIRATION—THE HERING-BREUER INFLATION REFLEX • In addition to the central nervous system respiratory control mechanisms operating entirely within the brain stem, sensory nerve signals from the lungs also help control respiration. • Most importantly, located in the muscular portions of the walls of the bronchi and bronchioles throughout the lungs are stretch receptors that transmit signals through the vagi into the dorsal respiratory group of neurons when the lungs become overstretched. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 LUNG INFLATION SIGNALS LIMIT INSPIRATION—THE HERING-BREUER INFLATION REFLEX • These signals affect inspiration in much the same way as signals from the pneumotaxic center; that is, when the lungs become overinflated, the stretch receptors activate an appropriate feedback response that “switches off the inspiratory ramp and thus stops further inspiration. • This mechanism is called the Hering-Breuer inflation reflex. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 CHEMICAL CONTROL OF RESPIRATION • The ultimate goal of respiration is to maintain proper concentrations of • O2 , • CO2 , • H+ in the tissues. • It is fortunate, therefore, that respiratory activity is highly responsive to changes in each of these substances. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 CHEMICAL CONTROL OF RESPIRATION • Excess CO2 or excess H+ in the blood mainly act directly on the respiratory center, • causing greatly increased strength of both the inspiratory and the expiratory motor signals to the respiratory muscles. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist 01 CHEMICAL CONTROL OF RESPIRATION • Oxygen, in contrast, does not have a major direct effect on the respiratory center of the brain in controlling respiration. • Instead, it acts almost entirely on peripheral chemoreceptors located in the carotid and aortic bodies, • and these chemoreceptors in turn transmit appropriate nervous signals to the respiratory center for control of respiration. : O-1137-2015 : https://orcid.org/0000-0002-7761-2617 : [email protected] : +90 505 434 40 89 brain_ist