Physiology 1 - Lecture no 12 PDF

PAGE 1 https://www.umfst.ro Physiology 1 - Lecture no 12 https://edu.umch.de PULMONARY EDEMA. PLEURAL FLUID. PRINCIPLES OF GAS Associate Prof. Dr. Adina Stoian May...

PAGE 1 https://www.umfst.ro Physiology 1 - Lecture no 12 https://edu.umch.de PULMONARY EDEMA. PLEURAL FLUID. PRINCIPLES OF GAS Associate Prof. Dr. Adina Stoian May EXCHANGE; DIFFUSION OF OXYGEN AND CARBON DIOXIDE 2024 THROUGH THE RESPIRATORY MEMBRANE. TRANSPORT OF OXYGEN AND CARBON DIOXIDE IN BLOOD AND TISSUE FLUIDS. Pulmonary Edema PAGE 2 Pulmonary edema occurs in the same way that edema occurs elsewhere in the body. Any factor that: increases fluid filtration out of the pulmonary capillaries impedes pulmonary lymphatic function causes the pulmonary interstitial fluid pressure to rise from the negative range into the positive range will tend to cause filling of the pulmonary interstitial spaces and alveoli with free fluid. The most common causes of pulmonary edema: PAGE 3 Left-sided heart failure or Damage to the pulmonary mitral valve disease, with blood capillary membranes Consequences: consequent great increases caused by in pulmonary venous pressure infections such as rapid leakage of plasma pulmonary capillary pneumonia proteins and fluid out of the pressure by breathing noxious capillaries and into the lung flooding of the interstitial substances such as chlorine interstitial spaces and spaces and alveoli gas or sulfur dioxide gas alveoli = > ARDS Rapidity of Death in Persons With Acute Pulmonary Edema PAGE 4 When the pulmonary capillary In acute left-sided heart failure pressure rises lethal pulmonary edema can in which the pulmonary occur within hours capillary pressure OR even within 20 to 30 occasionally does rise to 50 minutes if the capillary mm Hg, pressure rises 25 to 30 mm death may ensue in less than Hg above the safety factor 30 minutes as a result of level. acute pulmonary edema. Fluid in the Pleural Cavity PAGE 5 When the lungs expand and To facilitate this movement a contract during normal The next figure shows the thin layer of mucoid fluid breathing, they slide back dynamics of fluid exchange lies between the parietal and forth within the pleural in the pleural space. and visceral pleurae. cavity. The pleural membrane: These fluids: is a porous, mesenchymal, serous carry tissue proteins with them membrane giving the pleural fluid a mucoid through which small amounts of characteristic interstitial fluid transude continually which is what allows extremely easy into the pleural space. slippage of the moving lungs.  PAGE 6 Pulmonary Circulation, Pulmonary Edema, and Pleural Fluid Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 39, 503- 510 Dynamics of fluid exchange in the intrapleural space. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Fluid in the Pleural Cavity PAGE 7 The total amount of fluid in each pleural cavity is normally slight—only a few milliliters. The excess fluid is pumped away by the mediastinum; lymphatic vessels opening directly from the superior surface of the diaphragm; the pleural cavity into the following: the lateral surfaces of the parietal pleura. The pleural space —the space between the parietal and visceral pleurae—is called a potential space because it normally is so narrow that it is not obviously a physical space. Negative Pressure in Pleural Fluid PAGE 8 A negative force is always required on the outside of the lungs to keep the lungs expanded. This force is provided by negative pressure in the normal pleural space. The basic cause of this negative pressure is pumping of fluid from the space by the lymphatics is also the basis of the negative pressure found in most tissue spaces of the body. Because the normal collapse tendency of the lungs is about −4 mm Hg, the pleural fluid pressure must always be at least as negative as −4 mm Hg to keep the lungs expanded. Pleural Effusion—Collection of Large Amounts of Free Fluid PAGE 9 in the Pleural Space blockage of lymphatic drainage from the pleural cavity. cardiac failure, which causes excessively high peripheral and pulmonary capillary pressures, leading to excessive transudation of fluid into the pleural cavity. greatly reduced plasma colloid osmotic pressure, thus allowing excessive transudation of fluid. 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. PRINCIPLES OF GAS EXCHANGE PAGE 10 After the alveoli are ventilated with fresh air, the ? In respiratory physiology next step in respiration is: diffusion of oxygen (O2) The process of diffusion is the basic mechanism by from the alveoli into the simply the random motion which diffusion occurs pulmonary blood of molecules in all the rate at which it occurs, diffusion of carbon dioxide directions through the which is a much more (CO2) in the opposite respiratory membrane and complex issue direction, out of the blood adjacent fluids. into the alveoli. Physics of Gas Diffusion and Gas Partial Pressures PAGE 11 Molecular Basis of Gas Diffusion For diffusion to occur, there All the gases of concern in must be a source of energy. respiratory physiology are This is also true of gases This source of energy is provided by simple molecules that are free dissolved in the fluids and the kinetic motion of the molecules. to move among one another tissues of the body. Except at absolute zero temperature, by diffusion. all molecules of all matter are continually undergoing motion. For free molecules that are not They then bounce away in new physically attached to others, In this way, the molecules directions and continue moving this means linear movement at move rapidly and randomly until they strike other high velocity until they strike among one another. molecules again. other molecules. Net Diffusion of a Gas in One Direction—Effect of a PAGE 12 Concentration Gradient If a gas chamber or solution has a high concentration of a particular gas at one end of the chamber and a low concentration at the other end, as shown in the next figure, net diffusion of the gas will occur from the high-concentration area toward the low-concentration area. The reason is that there are far more molecules at end A of the chamber to diffuse toward end B than there are molecules to diffuse in the opposite direction. Therefore, the rates of diffusion in each of the two directions are proportionately different, as demonstrated by the lengths of the arrows in the figure.  PAGE 13 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 Diffusion of oxygen from one end of a chamber to the other. The difference between the lengths of the arrows represents net diffusion. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Gas Pressures in a Mixture of Gases—Partial Pressures of PAGE 14 Individual Gases Pressure is caused by multiple impacts of moving molecules against a surface. The pressure of a gas acting on the surfaces of the respiratory passages and alveoli is proportional to the summated force of impact of all the molecules of that gas striking the surface at any given instant. This means that the pressure is directly proportional to the concentration of the gas molecules. Gas Pressures in a Mixture of Gases—Partial Pressures of PAGE 15 Individual Gases The rate of diffusion of each of these gases is directly In respiratory physiology, one proportional to the pressure deals with mixtures of gases caused by that gas alone, which is called the partial pressure of that gas. Oxygen Nitrogen Carbon dioxide Concept of partial pressure of the gas PAGE 16 Consider air, which has an approximate composition of The total pressure of this mixture at sea level averages 760 mm Hg. 79% nitrogen and 21% oxygen. 79% of the 760 mm Hg is caused by nitrogen (600 mm Hg) Each gas contributes to the total 21% by O 2 (160 mm Hg). pressure in direct proportion to The partial pressure of nitrogen in the mixture is 600 mm Hg, The partial pressure of O 2 is 160 mm Hg; its concentration. 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 Po2 , Pco2 , Pn2 , Phe the symbols Po2 , Pco2 , Pn2 , Phe, and so forth. Pressures of Gases Dissolved in Water and Tissues PAGE 17 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. Factors That Determine Partial Pressure of a Gas Dissolved PAGE 18 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. 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. These relationships are expressed by the following formula, which is Henry’s law: Partial pressure=Concentration of dissolved gas / Solubility coefficient Diffusion of Gases Between Gas Phase in Alveoli and PAGE 19 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. 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. But, in which direction will net diffusion of the gas occur? PAGE 20 The answer is that net diffusion is determined by the difference between the two partial pressures. If the partial pressure is greater in the gas phase in the alveoli, as is normally true for oxygen, then more molecules will diffuse into the blood than in the other direction. If the partial pressure of the gas is greater in the dissolved state in the blood, which is normally true for CO2 , then net diffusion will occur toward the gas phase in the alveoli. Pressure Difference Causes Net Diffusion of Gases PAGE 21 Through Fluids The net diffusion of gas from the area of high pressure to the area of low pressure is It is clear that when the partial pressure of equal to the number of molecules a gas is greater in one area than in another bouncing in this forward direction minus area, there will be net diffusion from the the number bouncing in the opposite high-pressure area toward the low- direction, which is proportional to the gas pressure area. partial pressure difference between the two areas, called simply the pressure difference for causing diffusion.  PAGE 22 Dead Space. Anatomic Dead Space Alveolar ventilation is less than tidal volume and minute ventilation because part of every breath fills and remains in the conducting airways and does not reach the alveoli. This air within the conducting airways does not participate in gas exchange. The volume of air present in the conducting airways is called the anatomic dead space (V ds). The volume of air in the anatomic dead space is determined by the anatomy (size and number) of the conducting airways. In the normal adult, at functional residual capacity (FRC), the volume of gas contained in the conducting airways is approximately 100 to 200 mL, compared with the 3000 mL of gas in the entire lung. With each tidal breath (approximately 500 mL), fresh gas moves first into the conducting airways and then into the alveoli. Normally, dead space ventilation represents 20% to 30% of the minute ventilation. This dead space is called the anatomic dead space because it is due to wasted ventilation of airways that do not and cannot participate in gas exchange. Physiologic Dead Space Ventilation PAGE 23 Imagine a diseased lung in which some alveoli are not perfused but continue to be ventilated. These ventilated but not perfused areas of the lung, in a sense, act just like the conducting airways that are also ventilated but do not participate in gas exchange. The total volume of gas in each breath that does not participate in gas exchange is called the physiologic dead space ventilation. It includes the anatomic dead space and the dead space secondary to ventilated, but not perfused, alveoli or alveoli overventilated relative to the amount of perfusion. Thus the physiologic dead space is always as large as the anatomic dead space, and in the presence of disease it may be considerably larger. In healthy individuals the physiologic dead space normally represents 25% to 30% of the minute ventilation. Expired Air Is a Combination of Dead Space Air and Alveolar Air PAGE 24 The overall composition of expired air is determined by the following: the amount of the expired air that is dead space air; the amount that is alveolar air. The next figure shows the progressive changes in O2 and CO2 partial pressures in the expired air during the course of expiration. The first portion of this air, the dead space air from the respiratory passageways, is typical humidified air. Then, progressively more and more alveolar air becomes mixed with the dead space air until all the dead space air has finally been washed out, and nothing but alveolar air is expired at the end of expiration. Therefore, the method of collecting alveolar air for study is simply to collect a sample of the last portion of the expired air after forceful expiration has removed all the dead space air.  PAGE 25 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 Oxygen and carbon dioxide partial pressures ( Po2 and Pco2) in the various portions of normal expired air. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Diffusion of Gases Through the Respiratory Membrane PAGE 26 Respiratory Unit The next figure shows the respiratory unit (also called respiratory lobule), which is composed of a respiratory bronchiole, alveolar ducts and alveoli. There are about 300 million alveoli in the two lungs, and each alveolus has an average diameter of about 0.2 millimeter. The alveolar walls are extremely thin, and between the alveoli is an almost solid network of interconnecting capillaries, shown in the second next figure. 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.  PAGE 27 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 Respiratory unit. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved.  PAGE 28 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 A, Surface view of capillaries in an alveolar wall. B, Cross-sectional view of alveolar walls and their vascular supply. A, From Maloney JE, Castle BL: Pressure-diameter relations of capillaries and small blood vessels in frog lung. Respir Physiol... Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Structure of the Alveolar-Capillary Network PAGE 29 The sequential branching of the pulmonary arteries culminates in a dense mesh-like network of capillaries that surround alveoli. This alveolar-capillary network is composed of thin epithelial cells of the alveolus and endothelial cells of the capillaries and their supportive matrix, and it has an alveolar surface area of approximately 85 m2. The structural matrix and the tissue components of this alveolar-capillary network provide the only barrier between gas in the airway and blood in the capillary. The cells of this 1 to 2 µm thick barrier consist of type I alveolar epithelial cells positioned back-to-back with capillary endothelial cells. They are separated only by their respective basement membranes. Structure of the Alveolar-Capillary Network PAGE 30 Surrounded mostly by air, this alveolar-capillary network is an ideal environment for gas exchange. Red blood cells pass through the capillary component of this network in single file in less than 1 second, which is sufficient time for CO2 and O2 gas exchange. During conditions of increased metabolic activity (e.g., illness, physical activity) cardiac output increases and pulmonary capillary transit time decreases. Blood flows more rapidly through the pulmonary capillary bed. If the alveolar-capillary network is diseased, there may be insufficient time for adequate oxygen exchange. Structure of the Alveolar-Capillary Network PAGE 31 Hypoxemia may result. In addition to gas exchange, the alveolar-capillary network regulates the amount of fluid within the lung. At the pulmonary capillary level, the balance between hydrostatic and oncotic pressure across the wall of the capillary results in a small net movement of fluid out of the vessels into the interstitial space. The fluid is then removed from the lung interstitium by the lymphatic system and enters the circulation via the vena cava in the area of the lung hilum. In normal adults, an average of 30 mL of fluid per hour is returned to the circulation via this route. Structure of the Alveolar-Capillary Network PAGE 32 Introduction to the Respiratory System Koeppen, Bruce, Berne & Levy Physiology, 20, 431-443 Illustration of the anatomical relationship of the pulmonary artery, the bronchial artery, the airways, and the lymphatic vessels. A, Alveoli; AD, alveolar ducts; RB, respiratory bronchioles; TB, terminal bronchioles. Copyright © 2024 Copyright © 2024 by Elsevier. All rights reserved. The synergy of respiration and pulmonary circulation PAGE 33 The respiratory and circulatory systems function together to transport oxygen (O2) from the lungs to the tissues to sustain normal cellular activity and to transport carbon dioxide (CO2) from the tissues to the lungs for expiration. To enhance uptake and transport of these gases between the lungs and tissues, specialized mechanisms (e.g., binding of O2 and hemoglobin and HCO3− transport of CO2) have evolved that enable O2 uptake and CO2 expiration to occur simultaneously. To understand the mechanisms involved in the transport of these gases, gas diffusion properties, gas transport, and gas delivery mechanisms must be considered. The synergy of respiration and pulmonary circulation PAGE 34 Oxygen and Carbon Dioxide Transport Koeppen, Bruce, Berne & Levy Physiology, 24, 477-485 Oxygen (O2) and carbon dioxide (CO2) transport in arterial and venous blood. Oxygen in arterial blood is transferred from arterial capillaries to tissues. The flow rates for O2 and CO2 are shown for 1 L of blood. Copyright © 2024 Copyright © 2024 by Elsevier. All rights reserved. Diffusion of Gases Through the Respiratory Membrane and PAGE 35 Respiratory Unit Thus, it is obvious that the alveolar gases are in very close proximity to the blood of the pulmonary capillaries. 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. Respiratory Membrane – Alveolar – Capillary Membrane PAGE 36 The next figure shows the ultrastructure of the respiratory membrane drawn in cross section on the left and a red blood cell on the right. It also shows diffusion of O2 from the alveolus into the red blood cell and diffusion of CO2 in the opposite direction. Note the following different layers of the respiratory membrane:  PAGE 37 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 Ultrastructure of the alveolar respiratory membrane, shown in cross section. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. The layers of The Alveolar – Capillary Membrane PAGE 38 1. A layer of fluid containing surfactant that lines the alveolus and reduces the surface tension of alveolar fluid 2. The alveolar epithelium, composed of thin epithelial cells 3. An epithelial basement membrane 4. A thin interstitial space between the alveolar epithelium and capillary membrane 5. A capillary basement membrane that in many places fuses with the alveolar epithelial basement membrane 6. The capillary endothelial membrane The Alveolar – Capillary Membrane PAGE 39 Despite the large number of layers, the overall thickness of the respiratory membrane in some areas is as little as 0.2 micrometer and averages about 0.6 micrometer, except where there are cell nuclei. From histological studies, it has been estimated that the total surface area of the respiratory membrane is about 70 square meters in healthy men, which is equivalent to the floor area of a 25 × 30-foot room. The total quantity of blood in the capillaries of the lungs at any given instant is 60 to 140 ml. Now, imagine this small amount of blood spread over the entire surface of a 25 × 30-foot floor, and it is easy to understand the rapidity of the respiratory exchange of O2 and CO2. The Alveolar – Capillary Membrane PAGE 40 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 to pass through significant amounts of plasma as they diffuse between the alveolus and red blood cell. This also increases the rapidity of diffusion. Factors Affecting Rate of Gas Diffusion Through The PAGE 41 Alveolar-Capillary Membrane the thickness of the membrane; the surface area of the membrane; the diffusion coefficient of the gas in the substance of the membrane; the partial pressure difference of the gas between the two sides of the membrane. Factors Affecting Rate of Gas Diffusion Through The PAGE 42 Alveolar-Capillary Membrane The thickness of the respiratory membrane occasionally increases—for example, as a result of edema fluid in the interstitial space of the membrane and in the alveoli—so the respiratory gases must then diffuse not only through the membrane but also through this fluid. Some pulmonary diseases cause fibrosis of the lungs, which can increase the thickness of some portions of the respiratory membrane. Because the rate of diffusion through the membrane is inversely proportional to the thickness of the membrane, any factor that increases the thickness to more than two to three times normal can interfere significantly with normal respiratory exchange of gases. Factors Affecting Rate of Gas Diffusion Through The PAGE 43 Alveolar-Capillary Membrane The surface area of the respiratory membrane can be greatly decreased by many conditions. For example, removal of an entire lung decreases the total surface area to half-normal. The new alveolar chambers are much larger than the original alveoli, but the In emphysema , many of the alveoli coalesce, with dissolution of many total surface area of the respiratory membrane is often decreased as much alveolar walls. as fivefold because of loss of the alveolar walls. When the total surface area is decreased to about one-third to one-fourth normal, exchange of gases through the membrane is substantially impeded, even under resting conditions , and during competitive sports and other strenuous exercise, even the slightest decrease in surface area of the lungs can be a serious detriment to respiratory exchange of gases. Factors Affecting Rate of Gas Diffusion Through The PAGE 44 Alveolar-Capillary Membrane The diffusion coefficient for transfer of each gas through the respiratory membrane depends on the gas’s solubility in the membrane and, inversely, on the square root of the gas’s molecular weight. The rate of diffusion in the respiratory membrane is almost exactly the same as that in water. Therefore, for a given pressure difference, CO2 diffuses about 20 times as rapidly as O2. Oxygen diffuses about twice as rapidly as nitrogen. Factors Affecting Rate of Gas Diffusion Through The PAGE 45 Alveolar-Capillary Membrane The pressure difference across the respiratory membrane is the difference between the partial pressure of the gas in the alveoli and the partial pressure of the gas in the pulmonary capillary blood. Therefore, the difference between these two pressures is a measure of the net tendency for the gas molecules to move through the membrane. Factors Affecting Rate of Gas Diffusion Through The PAGE 46 Alveolar-Capillary Membrane When the partial pressure of a gas in the alveoli is greater than the pressure of the gas in the blood, as is true for O2 , net diffusion from the alveoli into the blood occurs. When the pressure of the gas in the blood is greater than the partial pressure in the alveoli, as is true for CO2 , net diffusion from the blood into the alveoli occurs. Diffusing Capacity of the Respiratory Membrane PAGE 47 The ability of the respiratory membrane to exchange a gas between the alveoli and pulmonary blood is expressed in All the factors discussed earlier that affect quantitative terms by the respiratory diffusion through the respiratory membrane’s diffusing capacity, which is membrane can affect this diffusing defined as the volume of a gas that will capacity. diffuse through the membrane each minute for a partial pressure difference of 1 mm Hg. Diffusing Capacity for Oxygen PAGE 48 In the average young man, the diffusing capacity for O2 under resting conditions averages 21 ml/min per mm Hg. In functional terms, what does this mean? The mean O2 pressure difference across the respiratory membrane during normal quiet breathing is about 11 mm Hg. Multiplying this pressure by the diffusing capacity (11 × 21) gives a total of about 230 ml of oxygen diffusing through the respiratory membrane each minute, which is equal to the rate at which the resting body uses O2. Increased Oxygen Diffusing Capacity During Exercise PAGE 49 During strenuous exercise or other conditions that greatly increase pulmonary blood flow and alveolar ventilation, the diffusing capacity for O2 increases to about three times the diffusing capacity under resting conditions. This increase is caused by several factors, including the following: opening up of many previously dormant pulmonary capillaries or extra dilation of already open capillaries, thereby increasing the surface area of the blood into which the O2 can diffuse; a better match between the ventilation of the alveoli and perfusion of the alveolar capillaries with blood, called the ventilation-perfusion ratio , explained later in this chapter. Therefore, during exercise, oxygenation of the blood is increased not only by increased alveolar ventilation but also by greater diffusing capacity of the respiratory membrane for transporting O2 into the blood. Diffusing Capacity for Carbon Dioxide PAGE 50 The diffusing capacity for CO2 has never been measured because CO2 diffuses through the respiratory membrane so rapidly that the average Pco2 in the pulmonary blood is not very different from the Pco 2 in the alveoli—the average difference is less than 1 mm Hg. With currently available techniques, this difference is too small to be measured. Diffusing Capacity for Carbon Dioxide PAGE 51 Nevertheless, measurements of diffusion of other gases have shown that the diffusing capacity varies directly with the diffusion coefficient of the particular gas. Because the diffusion coefficient of CO2 is slightly more than 20 times that of O2 , one would expect a diffusing capacity for CO2 under resting conditions of about 400 to 450 ml/min per mm Hg and during exercise of about 1200 to 1300 ml/min per mm Hg. The next figure compares the measured or calculated diffusing capacities of carbon monoxide, O2 , and CO2 at rest and during exercise, showing the extreme diffusing capacity of CO2 and the effect of exercise on the diffusing capacity of each of these gases.  PAGE 52 Principles of Gas Exchange; Diffusion of Oxygen and Carbon Dioxide Through the Respiratory Membrane Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 40, 511-520 Diffusing capacities for carbon monoxide, oxygen, and carbon dioxide in the normal lungs under resting conditions and during exercise. Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Effect of Ventilation-Perfusion Ratio on Alveolar Gas PAGE 53 Concentration This discussion made the In the previous lecture, we assumption that all the alveoli learned that two factors are ventilated equally, and determine the Po2 and Pco2 in that blood flow through the the alveoli: alveolar capillaries is the same for each alveolus. the rate of transfer of O2 and the rate of alveolar CO2 through the respiratory ventilation membrane. The Ventilation-Perfusion Ratio – V/Q PAGE 54 Even normally to some extent, and especially in many lung diseases, some areas of the lungs are well ventilated but have almost no blood flow, whereas other areas may have excellent blood flow but little or no ventilation. In either of these conditions, gas exchange through the respiratory membrane is seriously impaired, and the person may suffer severe respiratory distress, despite normal total ventilation and normal total pulmonary blood flow, but with the ventilation and blood flow going to different parts of the lungs. A highly quantitative concept has been developed to help us understand respiratory exchange when there is imbalance between alveolar ventilation and alveolar blood flow. This concept is called the ventilation-perfusion ratio. The Ventilation-Perfusion Ratio – V/Q PAGE 55 When V (alveolar ventilation) is normal for a given alveolus, and Q (blood flow) is also normal for the same alveolus, the ventilation-perfusion ratio (V/Q) is also said to be normal. When the ventilation (V) is zero, yet there is still perfusion (Q) of the alveolus, the V/Q is zero. When there is adequate ventilation (V) but zero perfusion (Q), the ratio V/Q is infinity. At a ratio of either zero or infinity, there is no exchange of gases through the respiratory membrane of the affected alveoli. Gas Exchange and Alveolar Partial Pressures When V/Q Is PAGE 56 Normal When there is both normal alveolar ventilation and normal alveolar capillary blood flow (normal alveolar perfusion), exchange of O2 and CO2 through the respiratory membrane is nearly optimal, and alveolar Po2 is normally at a level of 104 mm Hg, which lies between that of the inspired air (149 mm Hg) and that of venous blood (40 mm Hg). Likewise, alveolar Pco2 lies between two extremes; it is normally 40 mm Hg, in contrast to 45 mm Hg in venous blood and 0 mm Hg in inspired air. Thus, under normal conditions, the alveolar air Po2 averages 104 mmHg and the Pco2 averages 40 mm Hg. Aging PAGE 57 Aging affects both the structure and the function of the respiratory system. Lung growth, best measured by the forced expiratory volume after 1 second (FEV1), occurs throughout childhood and reaches a peak or maximum level at approximately 18 years of age in women and 21 years of age in men. Lung function then declines, with a loss in FEV1 of approximately 30 mL/year. This loss occurs due to the progressive loss of alveolar elastic recoil combined with costal cartilage calcification, decreased intervertebral space, and greater spinal curvature. Aging PAGE 58 Alveolar Ventilation Cloutier, Michelle M., MD, Respiratory Physiology, 5, 60-73 Changes in forced vital capacity (FVC) and forced expiratory volume after 1 second (FEV 1) with age in normal men and women. Peak lung function occurs around 18 years of age for women and 21 years of age for men. Redrawn from Knudson RJ, Slatin RC... Copyright © 2019 Copyright © 2019 Elsevier Inc. All Rights Reserved. Transport of Oxygen from the Lungs to the Body Tissues PAGE 59 Thus, O2 diffuses from the alveoli Gases can move from one point to into the pulmonary capillary In the other tissues of the body, a another by diffusion, and the blood because the oxygen partial higher Po2 in the capillary blood cause of this movement is always pressure (Po2) in the alveoli is than in the tissues causes O2 to a partial pressure difference from greater than the Po2 in the diffuse into the surrounding cells. the first point to the next. pulmonary capillary blood. Conversely, when O2 is After blood flows to the lungs, the metabolized in the cells to form CO2 diffuses out of the blood into CO2, the intracellular CO2 partial the alveoli because the Pco2 in the pressure (Pco2) rises, causing pulmonary capillary blood is CO2 to diffuse into the tissue greater than that in the alveoli. capillaries. Diffusion of Oxygen from the Alveoli to the Pulmonary PAGE 60 Capillary Blood The top part of the figure shows a pulmonary alveolus adjacent to a pulmonary capillary, demonstrating diffusion of O2 between alveolar air and pulmonary blood. The Po2 of the gaseous O2 in the alveolus averages 104 mm Hg, whereas the Po2 of the venous blood entering the pulmonary capillary at its arterial end averages only 40 mm Hg because a large amount of O2 was removed from this blood as it passed through the peripheral tissues. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Diffusion of Oxygen from the Alveoli to the Pulmonary PAGE 61 Capillary Blood Therefore, the initial pressure difference that causes O2 to diffuse into the pulmonary capillary is 104 − 40 mm Hg, or 64 mm Hg. In the graph at the bottom of the figure, the curve shows the rapid rise in blood Po2 as the blood passes through the capillary The blood Po2 rises almost to that of the alveolar air by the time the blood has moved a third of the distance through the capillary, becoming almost 104 mm Hg. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Uptake of Oxygen by the Pulmonary Blood During Exercise PAGE 62 During strenuous exercise, a person’s body may require as much as 20 times the normal amount of oxygen. Also, because of increased cardiac output during exercise, the time that the blood remains in the pulmonary capillary may be reduced to less than one-half normal. Yet, because of the great safety factor for diffusion of O2 through the pulmonary membrane, the blood still becomes almost saturated with O2 by the time it leaves the pulmonary capillaries. Uptake of Oxygen by the Pulmonary Blood During Exercise PAGE 63 First, the diffusing capacity for O2 increases almost threefold during exercise. This results mainly from increased surface area of capillaries participating in the diffusion and also from a more nearly ideal ventilation-perfusion ratio in the upper part of the lungs. Second, the blood becomes almost saturated with O2 by the time it has passed through one-third of the pulmonary capillary, and little additional O2 normally enters the blood during the latter two-thirds of its transit. That is, the blood normally stays in the lung capillaries about three times as long as needed to cause full oxygenation. Therefore, during exercise, even with a shortened time of exposure in the capillaries, the blood can still become almost fully oxygenated. Transport of Oxygen in Arterial Blood PAGE 64 About 98% of the blood that enters the left atrium from the lungs has just passed through the alveolar capillaries and has become oxygenated up to a Po2 of about 104 mm Hg. Another 2% of the blood has passed from the aorta through the bronchial circulation, which supplies mainly the deep tissues of the lungs and is not exposed to lung air. This blood flow is called shunt flow, meaning that blood is shunted past the gas exchange areas. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Transport of Oxygen in Arterial Blood PAGE 65 On leaving the lungs, the Po2 of the shunt blood is approximately that of normal systemic venous blood—about 40 mm Hg. When this blood combines in the pulmonary veins with the oxygenated blood from the alveolar capillaries, this so-called venous admixture of blood causes the Po2 of the blood entering the left heart and pumped into the aorta to fall to about 95 mm Hg. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Diffusion of Oxygen from the Peripheral Capillaries into PAGE 66 the Tissue Fluid When the arterial blood reaches the peripheral tissues, its PO 2 in the capillaries is still 95 mm Hg. The Po2 in the interstitial fluid that surrounds the tissue cells averages only 40 mm Hg. Thus, there is a large initial pressure difference that causes O2 to diffuse rapidly from the capillary blood into the tissues—so rapidly that the capillary Po2 falls almost to equal the 40-mm Hg pressure in the interstitium. Therefore, the Po2 of the blood leaving the tissue capillaries and entering the systemic veins is also about 40 mm Hg. Increasing Tissue Metabolism Decreases Interstitial Fluid PAGE 67 Po2 If the cells use more O2 for metabolism than normal, the interstitial fluid Po2 is reduced. the rate of O2 transport to the tissues in the In summary, tissue Po2 is blood determined by a balance between the rate at which the O2 is used by the tissues. Diffusion of Oxygen from Peripheral Capillaries to Tissue PAGE 68 Cells Oxygen is always being used by the cells. Therefore, the intracellular Po2 in peripheral tissues remains lower than the Po2 in peripheral capillaries. Also, in many cases, there is considerable physical distance between the capillaries and cells. Therefore, the normal intracellular Po2 ranges from as low as 5 mm Hg to as high as 40 mm Hg, averaging (by direct measurement in experimental animals) 23 mm Hg. Because only 1 to 3 mm Hg of O2 pressure is normally required for full support of the chemical processes that use oxygen in the cell, even this low intracellular Po2 of 23 mm Hg is more than adequate and provides a large safety factor. Diffusion of Co 2 From Peripheral Tissue Cells into PAGE 69 Capillaries and From Pulmonary Capillaries into Alveoli When O2 is used by the cells, virtually all of it becomes CO2, and this transformation increases the intracellular Pco2; because of this elevated tissue cell Pco2, CO2 diffuses from the cells into the capillaries and is then carried by the blood to the lungs. In the lungs, it diffuses from the pulmonary capillaries into the alveoli and is expired. Thus, at each point in the gas transport chain, CO2 diffuses in the direction exactly opposite to the diffusion of O2. Yet, there is one major difference between diffusion of CO2 and of O2 — CO2 can diffuse about 20 times as rapidly as O2. Diffusion of Co 2 From Peripheral Tissue Cells into PAGE 70 Capillaries and From Pulmonary Capillaries into Alveoli Therefore, the pressure differences required to cause CO2 diffusion are, in each case, far less than the pressure differences required to cause O2 diffusion. The CO2 pressures are approximately the following: 1. Intracellular Pco2, 46 mm Hg; interstitial Pco2, 45 mm Hg. Thus, there is only a 1 mm Hg pressure differential. 2. Pco2 of the arterial blood entering the tissues, 40 mm Hg; Pco2 of the venous blood leaving the tissues, 45 mm Hg. Thus, the tissue capillary blood comes almost exactly to equilibrium with the interstitial Pco2 of 45 mm Hg. Diffusion of Co 2 From Peripheral Tissue Cells into PAGE 71 Capillaries and From Pulmonary Capillaries into Alveoli 3. Pco2 of the blood entering the pulmonary capillaries at the arterial end, 45 mm Hg; Pco2 of the alveolar air, 40 mm Hg. Thus, only a 5 mm Hg pressure difference causes all the required CO2 diffusion out of the pulmonary capillaries into the alveoli. Furthermore, the Pco2 of the pulmonary capillary blood falls to almost exactly equal the alveolar Pco2 of 40 mm Hg before it has passed more than about one-third of the distance through the capillaries. This is the same effect that was observed earlier for O2 diffusion, except that it is in the opposite direction. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Role of Hemoglobin in Oxygen Transport PAGE 72 Normally, about 97% of the oxygen transported from the lungs to the tissues is carried in chemical combination with hemoglobin in the red blood cells. The remaining 3% is transported in the dissolved state in the water of the plasma and blood cells. Thus, under normal conditions, oxygen is carried to the tissues almost entirely by hemoglobin. Reversible Combination of O 2 With Hemoglobin PAGE 73 The O2 molecule combines loosely and reversibly with the heme portion of hemoglobin. When Po2 is high, as in the pulmonary capillaries, O2 binds with hemoglobin, but when Po2 is low, as in the tissue capillaries, O2 is released from hemoglobin. This is the basis for almost all O2 transport from the lungs to the tissues. Factors That Shift the Oxygen-Hemoglobin Dissociation PAGE 74 Curve—Their Importance for Oxygen Transport Several factors can displace the dissociation curve in one direction or the other. This figure shows that when the blood becomes slightly acidic, with the pH decreasing from the normal value of 7.4 to 7.2, the O2-hemoglobin dissociation curve shifts, on average, about 15% to the right. Conversely, an increase in pH from the normal 7.4 to 7.6 shifts the curve a similar amount to the left. Transport of Oxygen and Carbon Dioxide in Blood and Tissue Fluids Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 41, 521-530 Copyright © 2021 Copyright © 2021 by Elsevier, Inc. All rights reserved. Factors That Shift the Oxygen-Hemoglobin Dissociation PAGE 75 Curve—Their Importance for Oxygen Transport In addition to pH changes, several other factors are known to shift the curve. Three of these, which shift the curve to the right are the following: (3) increased 2,3-biphosphoglycerate (BPG), a metabolically important phosphate compound present (1) increased CO 2 concentration; (2) increased blood temperature; and in the blood in different concentrations under different metabolic conditions. Increased Delivery of Oxygen to Tissues When CO 2 and H + Shift PAGE 76 the Oxygen-Hemoglobin Dissociation Curve—the Bohr Effect A shift of the oxygen-hemoglobin dissociation curve to the right in response to increases in blood CO2 and This is called the Bohr effect, which can H + levels have a significant effect by be explained as follows. enhancing the release of O2 from the blood in the tissues and enhancing oxygenation of the blood in the lungs. This diffusion increases the blood Pco2, As the blood passes through the which in turn raises blood tissues, CO2 diffuses from tissue cells H2CO3 (carbonic acid) and into the blood. H + concentration. Increased Delivery of Oxygen to Tissues When CO 2 and PAGE 77 H + Shift the Oxygen-Hemoglobin Dissociation Curve—the Bohr Effect These effects shift the O2-hemoglobin dissociation curve to the right and downward, forcing O2 away from the hemoglobin and therefore delivering increased amounts of O2 to the tissues. Exactly the opposite effects occur in the lungs, where CO2 diffuses from the blood into alveoli. This diffusion reduces blood Pco2 and H+ concentration, shifting the O2-hemoglobin dissociation curve to the left and upward. Therefore, the quantity of O2 that binds with the hemoglobin at any given alveolar Po2 becomes considerably increased, thus allowing greater O2 transport to the tissues. Transport of Co2 in Blood PAGE 78 Transport of CO2 by the blood is not nearly as problematical as transport of O2 is because even in the most abnormal conditions, CO2 can usually be transported in far greater quantities than can O2. However, the amount of CO2 in the blood has a lot to do with the acid–base balance of the body fluids. Under normal resting conditions, an average of 4 ml of CO 2 are transported from the tissues to the lungs in each 100 ml of blood. Transport of CO 2 in Combination With Hemoglobin and PAGE 79 Plasma Proteins—Carbaminohemoglobin In addition to reacting with water, CO2 reacts directly with amine radicals of the hemoglobin molecule to form the compound carbaminohemoglobin (CO2Hgb). This combination of CO2 and hemoglobin is a reversible reaction that occurs with a loose bond, so the CO2 is easily released into the alveoli, where the Pco2 is lower than in the pulmonary capillaries. A small amount of CO2 also reacts in the same way with the plasma proteins in tissue capillaries. This reaction is much less significant for the transport of CO2 because the quantity of these proteins in the blood is only one-fourth as great as the quantity of hemoglobin. Transport of CO 2 in Combination With Hemoglobin and PAGE 80 Plasma Proteins—Carbaminohemoglobin The quantity of CO2 that can be carried from the peripheral tissues to the lungs by carbamino combination with hemoglobin and plasma proteins is about 30% of the total quantity transported—that is, normally about 1.5 ml of CO2 in each 100 ml of blood. However, because this reaction is much slower than the reaction of CO2 with water inside the red blood cells, it is doubtful that under normal conditions this carbamino mechanism transports more than 20% of the total CO2.  PAGE 81 [email protected] QUESTIONS?