Model to facilitate studying oxygen and carbon dioxide transport KERMIT A. GAAR, JR. Department of Physiology and Biophysics, School of Medicine, Louisiana State University Medical Center, Shreveport, Louisiana 71130-3932 S6 1043-4046/91 $1.50 Copyright 0 1991 the American Physiological Society Downloaded from http://advan.physiology.org/ by 10.220.33.2 on April 20, 2017 body do not change. In order for this steady-state condition to be maintained, there must always be a parity between 1) the rate of lung ventilation, 2) the rate of tissue perfusion, and 3) the rate of tissue utilization of oxygen. If any one of these changes, even slightly, then the concentrations of the gases in the body will change also. Furthermore, the “rate of tissue perfusion” is meant to include both the rate of oxygen delivery to and the rate of carbon dioxide removal from the tissues. This is determined by the product of blood flow rate and the blood concentrations of oxygen or carbon dioxide. The latter are determined mainly by the transport “capacity” of the blood for these gases,which was mentioned above in conjunction with blood hemoglobin concentration. These and other factors can be studied with the 02/ CO2 Transport Model. This is an improved version of an earlier model program used to study oxygen transport that was originally written in the Applesoft BASIC lancomputer model; blood gases; cardiopulmonary physiology guage for use with the Apple II series of microcomputers (1). Carbon dioxide transport was added to this new revision, and a second version of the model has been WHEN WE THINK of respiration, what usually comes to developed using QuickBASIC (Microsoft) for use with mind is the movement of air into and out of the lungs. the IBM-PC and compatible microcomputers. This is important, because it allows for oxygen absorpThe model program was constructed for the purpose tion and carbon dioxide removal where the blood con- of facilitating the study and understanding of basic cartacts the respiratory membrane. However, it is no less diopulmonary principles of oxygen and carbon dioxide important to think of respiration in terms of the carditransport. It is intended for use as a supplement to basic ovascular system, which acts to transport the blood gases instruction, mainly by medical and graduate students at between the lungs and the tissues. an introductory level. This might be accomplished in Transport of oxygen and carbon dioxide involves three several different ways, depending on the requirements of main areas: these gases are transported between the the students or instructors and the facilities available. atmosphere and alveoli by lung ventilation, between One example would be to use the model to demonstrate lungs and tissues via circulating blood, and between physiological simulations in a classroom setting. This tissue capillaries and cells by the diffusion process (Fig. approach is especially useful if microcomputer facilities 1). This would not be possible were it not for the presence are limited. However, if sufficient microcomputers are of hemoglobin in the blood. Because oxygen is only available for access by the students, then they can be slightly soluble in the water of the blood, its combination allowed to work their way through the exercises provided. with hemoglobin increases the oxygen transport capacity The instructor might also want to supplement these with of blood -60-fold. Carbon dioxide is -20 times more additional exercises and/or study questions. water soluble than oxygen, but its transport also depends The physiological principles of the respiratory model heavily on hemoglobin. are based on the concept of a normal or “ideal” lung in Under normal conditions, the amount of oxygen that which there is no inequality of ventilation/perfusion to moves from the atmosphere to the tissues is determined impair gas exchange, as is often found in diseased lungs. by the rate at which the tissues use oxygen. This also In effect, the lung is modeled as a single large alveolus determines the amount of carbon dioxide that moves in with one blood supply instead of the many smaller subthe opposite direction. In a normal resting individual, units that actually exist. An analogous situation is conthe rate of oxygen use and carbon dioxide production is sidered to be present in the tissues where gas exchange constant, and the concentrations of these gases in the occurs. In addition, the effects of pH, temperature, etc., GAAR, KERMIT A., JR. Model to facilitate studying oxygen and carbon dioxide transport. Am. J. Physiol. 260 (Adv. Physiol. Educ. 5): S6-S9, 1991.-A simple model has been constructed for microcomputer (PC) simulations involving basic cardiopulmonary principles of oxygen transport. Students can change parameters such as metabolic rate, blood hemoglobin concentration, barometric pressure, air composition, etc., and study parameter effects on blood gas concentrations and partial pressures. An important feature of the model program is that there are no negative feedback controls to maintain homeostasis. However, after a perturbation has been introduced, adjustments can be made to appropriate variables to correct for abnormal effects. For example, ventilation rate and blood hemoglobin concentration might be adjusted to compensate for low atmospheric oxygen. Because these do not change automatically in the model program, learning is enhanced when the student has to make the appropriate adjustments needed to correct disturbances in the blood gases that follow a perturbation. MODEL OF OXYGEN AND CARBON . Am Capillaries \ variables is shown in Fig. 2. A summary listing of the values of the important model parameters and variables can be printed at any time during a simulation. For convenience, the model program is completely menu driven. A simulation can be interrupted at any time and a menu will appear on the screen. The menu gives a list of different options from which a selection can be made, as follows: 1) resuming the simulation without changing parameter values, 2) changing parameter values and resuming the simulation, 3) printing current data to the screen or a printer, 4) ending the current simulation and starting over with a new simulation, and 5) quitting the simulation session. Whenever option 2 is selected the operator is prompted to make changes in the model parameters; an example of this process is shown in Fig. 3. Adjustments can be made to pulmonary ventilation, cardiac output, and the rate of oxygen use by the tissues. (An important physiological concept that the model reinforces is the fact that parity between these three basic factors is necessary for the blood and tissue concentrations of the important respiratory gasesto remain completely normal.) Another factor that can be adjusted is the blood hemoglobin \ Circulatory Tissue Cells 1. Diagram and carbon dioxide FIG. s7 TRANSPORT TORR of scheme used by body for transport between atmosphere and body tissues. of oxygen on oxygen-to-hemoglobin binding have been purposely omitted, because they would have increased the model’s complexity without significantly enhancing its heuristic value. IOO- ......... PVC02 PaC02 pa02 . . .. . . .. . .. . ..._............_......._... ............................................................. pvo2 t FEATURES OF THE O&O2 TRANSPORT MODEL The OS/COPTransport Model program was formulated using normal physiological values for an average adult human individual. Physiological data have been preset in the model program and do not have to be entered initially when a simulation is begun. Therefore a simulation can start immediately when the model program is run. Complete documentation of the model and instructions for performing some special selected physiological simulations have been prepared and are available for distribution with the model program. For example, one can examine the effects of a change in the barometric pressure, such as occurs when one ascends a mountain or descends underwater (deep-sea diving), or one can study the effects of increased metabolism (exercise). Other studies could be the effects of oxygen therapy on acute heart failure or on acute respiratory failure. The model has several convenient features to facilitate these kinds of studies. One of the most important features is the presentation of important data in graphic form. During a simulation the numerical values of arterial and venous blood oxygen concentrations and the oxygen and carbon dioxide partial pressures are presented on the video monitor and updated with each iteration while the model program is running. In addition, the arterial and venous blood oxygen and carbon dioxide partial pressures are plotted graphically on the screen as a function of time. A sample output of these 0- 1 I I 5 10 15 I I 20 Ca02 Cv02 Pa02 PvO2 17.98 12.98 55 39 25 Min PVC02 PaC02 75 80 2. Graphical output of a simulation as it would appear on a monochrome viaeo monitor. I o proauce tnese results, pulmonary ventilation was lowered to one-half normal at time indicated by arrow. Four curves shown changing with time represent 4 blood gas tensions (in Torr): P ao,, arterial blood oxygen tension; Pvo,, venous blood oxygen tension; Pace,, arterial blood carbon dioxide tension; Pvco2, venous blood carbon dioxide tension. Corresponding numerical values shown under graph are updated with each iteration. These also include arterial and venous blood oxygen concentrations, Cao, and Cvo,, which are not plotted on graph. FIG. * 1 -1 n-i 1 11 11 CHANGE ALVEOLAR CHANGE INSPIRED OXYGEN PRESSURE CHANGE CARDIAC OUTPUT ? (Y (Y OR OR N) N) : N : N CHANGE OXYGEN ? (Y OR N) : N CHANGE HEMOGLOBIN (Y OR N) : Y HEMOGLOBIN VENTILATION 1 DEMAND HEMOGLOBIN ARE THESE VALUES ? NOW ( 15 CONCENTRATION CORRECT 3 ? : N 3 CONCENTRATION CONCENTRATION NEW RATE ? (Y OR N) (Y OR : ) G/DL 10 N) : Y FIG. 3. Facsimile of type of output presented on video screen when option 2 is selected from previous screen menu as described in text. In example shown, only blood hemoglobin was changed before resuming simulation. Downloaded from http://advan.physiology.org/ by 10.220.33.2 on April 20, 2017 c / DIOXIDE S8 MODEL OF OXYGEN AND CARBON DIOXIDE TRANSPORT of carbon dioxide transported. The relative importance of the above parameters to total carbon dioxide transport can be seen graphically in Fig. 4. At normal carbon dioxide production, ventilation has the greatest effect. Blood flow is not shown, but it is about equal in effect to blood carbon dioxide transport capacity, which is mainly determined by blood hemoglobin concentration. For example, lowering either blood hemoglobin concentration or cardiac output to one-third normal should cause Pv co, to increase from a normal value of 45 Torr to -53-55 Torr. (Note also that although Pvco, has risen, the total blood carbon dioxide concentration has fallen.) To summarize, because Pvco, is also an important indicator of the body tissue PCO~ level, total body stores of carbon dioxide can be expected to increase whenever blood hemoglobin concentration or cardiac output falls below normal. This could be prevented, however, if there were a compensatory increase in ventilation. Use of the model in this manner to examine the relationship between these variables will further illustrate and reinforce the concept that a parity must be maintained to keep the blood and tissue gas levels from changing appreciably. AN EXAMPLE: USING THE MODEL CARBON DIOXIDE TRANSPORT IMPLEMENTING TO STUDY Carbon dioxide is formed as oxygen is metabolized by the body tissues. Consequently, tissue PCO~ depends on the rate at which oxygen is used and on the rate at which carbon dioxide is removed from the tissues by blood flow. There are two mechanisms that the cardiopulmonary system can use to help compensate for an elevated rate of carbon dioxide production due to acutely increased metabolism. One is to increase cardiac output via the body’s tissue blood flow autoregulation phenomenon (2). This carries the carbon dioxide away from the tissues as fast as it is formed. The other mechanism is to increase the rate of lung ventilation. The effect of this is not so obvious, but it works because tissue carbon dioxide levels are also affected by the PCO~ of the arterial blood entering the tissues. Furthermore, arterial blood PCO~ is determined by the rate of alveolar ventilation that removes carbon dioxide from the pulmonary blood. The tissues of the body contain large stores of carbon dioxide, and an average adult produces several hundred liters daily. It is especially important that none of this excess carbon dioxide be allowed to accumulate in the body. An important indicator of the level of carbon dioxide in the body is the PCO~ of the venous blood (Pvco,) leaving the tissues. This is because it is in equilibrium with the tissue Pco~. The important factors affecting tissue Pco~, as indicated by Pvco2, are given by equations found in the APPENDIX. Namely, these are 1) the rate of carbon dioxide formation, 2) the lung ventilation rate, 3) the tissue blood flow, and 4) the blood’s capacity to transport carbon dioxide. The latter is mainly determined by the blood hemoglobin concentration. Because hemoglobin binds with both carbon dioxide and with the hydrogen ions formed from carbonic acid, it is responsible for as much as 80-90% of the total amount WITH SIMULATION MODEL SOFTWARE System requirements for running the 02/COZ Transport Model software depend on the microcomputer and peripheral devices available. Applesoft BASIC in ROM TOTAL CO2 TRANSPORT loo- - 80 20 \SA= 1/2x QA=~xN 0 1 0 I 20 1 I 40 BLOOD 1 PC02 - I 60 TORR I 80 I N 1 100 4. Graph showing composite dynamic effects of alveolar ventilation rate (VA) and blood hemoglobin concentration ([Hb]) on total amount of carbon dioxide transported by blood. Total CO, transport means all of carbon dioxide in all its various forms that can be transported by blood. These data were obtained with the model under conditions that both cardiac output and tissue oxygen uptake remained unchanged from normal. FIG. Downloaded from http://advan.physiology.org/ by 10.220.33.2 on April 20, 2017 concentration. In addition, the oxygen pressure of the inspired air can be changed in two different ways. One way is to change the barometric pressure, and the other way is to change the inspired air oxygen concentration. There are no automatic (reflex) adjustments to breathing or blood flow built into the model program to counter the effects of the changes described above. Instead, the operator must supply any interventions needed to correct a disturbance, which is part of the learning experience provided by the model. For example, to keep blood gases within a normal range during exercise, one must learn to coordinate lung ventilation with changes in cardiac output. After having tried this manually for several simulations, one can better appreciate the body’s mechanisms that perform these functions automatically. Another important feature of the model program is incorporated into option 4. This option allows for beginning a new simulation with a new graph or leaving the graph of the previous simulation on the screen for overlaying the new simulation. This is useful if one wants to compare the results of two simulations. For example, one might study the effects of different types of interventions to correct a particular disturbance and have all recorded on the same graph. MODEL OF OXYGEN AND CARBON (read-only memory) and a minimum of 48 KB RAM (random access memory) are required for Apple microcomputers and compatibles. For the IBM-PC and other compatible microcomputers, MS-DOS or PC-DOS and either a Hercules monochrome graphics card or a color graphics card (IBM CGA, EGA, or VGA) is required. Color graphics is preferred but not necessary. Software for the model program is available on a standard 5.25 in. diskette. Requests for this software should specify either Apple or IBM format. Please send requests to K. A. Gaar, Jr., Dept. of Physiology and Biophysics, L. S. U. Medical Center, PO Box 33932, Shreveport, LA 71130-3932 [FAX: (318)-674-60051. APPENDIX DIOXIDE alent of the carbon dioxide-hemoglobin dissociation curve. Substituting rate of CO, production p&To, = Pace, + f(C0, cap) x cardiac output and assuming ho, equation is ho, = Cac0, + rate of CO, production cardiac output where Caco, and Cv co, are arterial and venous CO, concentrations, since Caco, = Pace, x f(C02 cap) and Cvco = Pvco x f(COz,,,), where CO zcap is the blood carbon dioxide-carrying capacity and Pa co, and Pvco, are arterial and venous Pco2, respectively. These two expressions are functionally the equiv- PAco, + rate of CO, production f(COs cap) x cardiac output pwoz from the alveolar ventilation K x rate of CO, production = alveolar ventilation rate -Iis the rate of CO, production, pvco, = vco2 rate of CO2 production P&o, = alveolar ventilation rate xK where PACT,is the alveolar partial pressure of carbon dioxide and K is a constant. The Fick equation (rearranged) for carbon dioxide is = Received rate of CO2 production f(COa Cap) x cardiac output then K alveolar ventilation + Address Louisiana Shreveport, equation rate 1 f(COz cap) x cardiac output 1 for reprint requests: Dept. of Physiology and Biophysics, State University Medical Center, School of Medicine in PO Box 33932, Shreveport, LA 71130-3932. 22 February 1990; accepted in final form 24 September 1990. REFERENCES 1. GAAR, K. A., JR. Oxygen transport: a simple model for study and examination. Physiologist 28: 412-415, 1985. 2. GAAR, K. A., JR. Oxygen transport: an analysis of short-term blood flow autoregulation. Comp. Biomed. Res. 20: 214-224, 1987. Downloaded from http://advan.physiology.org/ by 10.220.33.2 on April 20, 2017 ventilation that Pace, = PA~~~,then Substituting If ho2 The alveolar s9 TRANSPORT
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