Circulatory Physiology As a Country Doc Episode 3 and Venous Return Patrick Eggena, M.D.

Novateur Medmedia, LLC. Circulatory Physiology As a Country Doc Episode 3

Cardiac Output and Venous Return Patrick Eggena, M.D.

Novateur Medmedia, LLC.

i Copyright

This Episode is derived from:

Course in Cardiovascular Physiology by Patrick Eggena, M.D. © Copyright Novateur Medmedia, LLC. April 13, 2012 The United States Copyright Registration Number: PAu3-662-048

Ordering Information via iBooks: ISBN 978-0-9663441-2-7 Circulatory Physiology as a Country Doc, Episode 3: Cardiac Output and Venous Return

Contact Information: Novateur Medmedia, LLC 39 Terry Hill Road, Carmel, NY 10512 email: [email protected]

Credits: Oil Paintings by Bonnie Eggena, PsD. Music by Alan Goodman from his CD Under the Bed, Cancoll Music, copyright 2005 (with permission). Illustrations, movies, text, and lectures by Patrick Eggena, M.D.

Note: Knowledge in the basic and clinical sciences is constantly changing. The reader is advised to carefully consult the instruc- tions and informational material included in the package inserts of each drug or therapeutic agent before administration. The Country Doctor Series illustrates Physiological Principles and is not intended as a guide to Medical Therapeutics. Care has been taken to present correct information in this book, however, the author and publisher are not responsible for errors or omissions or for any consequence from application of the information in this work and make no warranty, expressed or implied, with re- spect to the contents of this publication or that its operation will be uninterrupted and error free on any particular recording de- vice. Novateur Medmedia, LLC shall not be held liable for any punitive damages resulting from the use or inability to use this work. This work is copyrighted by Novateur Medmedia, LLC. Except to store and retrieve one copy of the work, you may not reproduce, decompile, reverse engineer, modify or create derivative works without prior written permission by Novateur Medme- dia, LLC.

ii iii This Episode is dedicated to Bonnie and

to our children Kendra and Brandon and

to our grandchildren Basia, Anika, and August.

iv Foreword

This is the third of three episodes in the Circulatory Physiology Series. Each episode starts with a case where the student finds himself or herself in the imaginary world of a Country Doctor who is called upon to manage a clinical problem related to a 50-minute lec- ture given by the author to First Year Medical Students. Video tapes of these lectures are divided into short segments which are interwoven with relevant chapters of the author’s ebook, “Medical Physiology of the -Lung-Kidney.”

v About the Author

The author was born in London in 1938. His parents had fled from Germany in 1933 after his father was wrongly accused of burning down the Reichstag in Berlin as Hitler was rising to power. When War broke out, the author’s family was interned on the Isle of Man and, after the War ended, transported back to Germany. There the author grew up on a farm, attended Gymnasium, and emigrated to America at the age of 18.

Shortly after arriving in the US he was drafted into the Army and sent overseas where he served as a Medic. Upon returning to the US he attended Kenyon College and then Medical School at the University of Cincinnati. After serving as a house officer at the Cincinnati General Hospital he started a career in Medical Research, first as an NIH post-doctoral fellow at the Brookhaven National Laboratories and the University of Copenhagen and then as an Established Investigator of the American Heart Asso- ciation at the Mount Sinai School of Medicine. There he rose through the academic ranks to Professor of Physiology & Biophysics and served for 5 years as Acting Chair- man of the Department.

He chaired the Physiology Course for more than 20 years, taught all aspects of Physiology, and participated in the Art and Science of Medicine courses for First and Second Year Medical Students.

After retiring from teaching and research, the author returned to living on a farm with his wife and horses. Once a week he functions as an Emergency Physician in a nearby hospital --alone for the 16-hour night shift -- where he applies his understand- ing of Physiology to everyday patient care at the bedside.

Students at The Mount Sinai Medical School showed their appreciation for his teach- ing by awarding him The Excellence in Teaching Award on twelve occasions. Student comments and evaluations relating to the episodes published here are given on the next pages.

vi Student Evaluations

People Comments Report Printed: 4/5/2010 Patrick Eggena Comments about Educator: Please provide any constructive feedback about this educator.

Dr. Eggena is the best teacher I have ever had. I always felt secure that he would explain things thoroughly and logically and address our questions effectively. He is so familiar with the material, and its application to clinical practice, that I think he knows how to anticipate students' questions and confusion, and that makes him an excellent teacher. I also thought his text book and the sup- plemental practice programs online were invaluable resources. I feel that Eggena has given me a very firm grasp of the basics of cardiopulmonary physiology, and I'm very grateful to have had him as a teacher.

I thought Dr. Eggena was great. It was really helpful to have both his book and his computer pro- gram to supplement lectures - with 3 ways to learn the same information (and in the same order!) it is hard not to eventually understand each concept. The computer program with quizzes was espe- cially useful. Lectures were clear and well organized.

Dr. Eggena is one of the finest teachers I've yet experienced. His patience and thorough explana- tions allowed me a deep understanding of the material, while his focus on the practical aspects of each topic left me with a sense of competency that I will remember in the coming years. I enjoyed each of his lectures and have a deep respect for his dedication to providing study materials for stu- dents beyond the lectures and his wonderful text book. This has been an exciting and memorable learning experience.

Great lecturer, very clear.

Very clear lectures. Keep up the good work!

Great professor, very knowledgeable, patient, clear, concise.

Dr. Eggena was very thorough and clear in his explanations of cardiovascular and pulmonary physi- ology. His handouts were very helpful, as were his multimedia programs.

vii People Comments Report Printed: 9/28/2011 Patrick Eggena Comments about Educator: Please provide any constructive feedback about this edu- cator.

Oh my goodness, where to begin? Dr. Eggena is PHENOMENAL. He is so old-school using his projector and sharpie, drawing schematics and graphs he's obviously done a million times, and has such a story-teller's voice. But that's what makes him GREAT. More profes- sors shoiuld realize that maybe the powerpoint isn't the best format to teach, that maybe a less recently available form of technology would be a better teaching aide. More professors should give up trying to find a working dry erase board marker and switch to projectors and sharpies. On top of that, to have created a multimedia program and quizes that reinforce the material in such an entertaining way! Really I can't think of anything negative to say ex- cept that Dr. Eggena's lectures didn't extend to the whole of physiology and that his multime- dia program did not have anything on kidneys, endocrine, GI, etc. I found some of his lectures to be a little too fast paced, and unclear in some points. But he has a definite great rapport with the students, seems to really care about teaching, and his multimedia programs and multitude of practice questions were invaluable.

One of the best professors I have had yet. Very clear explinations, always happy to answer questions. A kind and approachable professor with clear clinical applications.

A truly masterful educator. And physician. excellent

Great instructor!

Eggena is the best. So clear! good

Fantastic teacher.

Once I got the hang of it, his outlines were helpful and it was a change to draw along during class rather than just typing away on a computer. His multimedia programs were also im- mensely helpful and the only reason I passed.

Dr. Eggena was a phenomenal educator and lecturer. I truly learned a lot from him regard- ing cardio and respiratory physiology. His online material was very helpful in studying for quizzes and exams. Thanks for a great semester!

Dr. Eggena was great. He went quickly but clearly through the material, and he always pre- sented concepts in terms of actual patient care, which made it all seem real.

viii Performance Analysis Report Printed: 9/28/2011 Report Notes: School of Medicine Evaluation System Subject: Patrick Eggena Activity Group: Physiology Starting Request Date: 12/01/2010 Ending Request Date: 09/28/2011 Location: Mt. Sinai

1 Clarity of presentation Using the lecture/educator list above to link this instructor with the lecture (s)he gave, please rate their clarity of presentation. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.35 2 5 138 1 to 5 0.74 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 1 1% 1 Unacceptable 0 0% 2 Below Average 3 2% 3 Average 13 9% 4 Very Good 55 40% 5 Superior 67 48%

2 Rapport with students Please rate this educator's rapport with students. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.62 3 5 138 1 to 5 0.52 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 1 1% 1 Unacceptable 0 0% 2 Below Average 0 0% 3 Average 2 1% 4 Very Good 48 35% 5 Superior 88 63%

3 Quality of Tracking Please rate this educator's overall quality of teaching. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.51 2 5 138 1 to 5 0.63 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 1 1% 1 Unacceptable 0 0% 2 Below Average 1 1% 3 Average 7 5% 4 Very Good 50 36% 5 Superior 80 58%

Page 1 of 1 Performance Analysis Report Printed: 4/5/2010 Report Notes: School of Medicine Evaluation System Subject: Patrick Eggena Activity Group: Physiology Time Frame Start Date between: 01/11/2010 and 04/05/2010

1 Clarity of presentation Please rate this educator's clarity of presentation. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.38 3 5 136 1 to 5 0.62 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 0 0% 1 Unacceptable 0 0% 2 Below Average 0 0% 3 Average 10 7% 4 Very Good 65 48% 5 Superior 61 45%

2 Rapport with students Please rate this educator's rapport with students. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.68 3 5 136 1 to 5 0.50 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 0 0% 1 Unacceptable 0 0% 2 Below Average 0 0% 3 Average 2 1% 4 Very Good 40 29% 5 Superior 94 69%

3 Quality of Tracking Please rate this educator's overall quality of teaching. Average: Minimum: Maximum: Non-Zero Count: Scale: Standard Dev: 4.57 3 5 136 1 to 5 0.58 Answer Value: Answer Choices: Choice Count: Percentage: 0 Unable to Evaluate 0 0% 1 Unacceptable 0 0% 2 Below Average 0 0% 3 Average 6 4% 4 Very Good 47 35% 5 Superior 83 61%

Page 1 of 1 1

The Country Doctor The Case

The Case

12 The Discussion

Kay: “Doc, it was good that you were holding on to him when he stood up and we took his .”

Doc: “Yes, Kay --we had to be prepared for him to faint. He did so once before when he stood up and hurt himself --could have happened again.”

Kay: “By how much does blood pressure have to drop before you call it or- thostatic hypotension?”

Doc: “Systolic pressure has to fall by at least 10%.”

Kay: “and increase by 10%?” Kay --your nurse is taking night courses to be- come a nurse practitioner. She comes along Doc: “Yes - Mr. Bach’s pulse increased in when you are making house calls. response to the pressure drop --after his baroreceptor reflex kicked in.” Doc: “That’s his problem. That’s why he Kay: “The sensors for this are in the ca- fainted. That’s his chief complaint. It’s why rotid sinus?” his daughter called us.”

Doc: “Yes --and in the wall of the aorta. Kay: “So as he stood up, blood pooled Stretch receptors. High pressure receptors in his legs, less returned to his heart, that are tonically active -- less so when his heart pumped less to his brain, and pressure drops. The response is fast he fainted. All due to a sluggish barore- --really fast.” ceptor!?” Kay: “But not with Mr. Bach. His reflex Doc: “Yes, Kay --that’s his problem in a nut- was slow --really slow.” shell.”

13 Kay: “His nerves from the carotid sinus something that depleted his blood vol- to the vasomotor center in the medulla ume? That can also cause orthostatic and back out to the veins were probably hypotension, can’t it -- Doc?” not conducting impulses fast enough?” Doc: “Yes for sure. Very common. If his Doc: “Could be. Patients with peripheral veins are nearly empty, tensing up on them neuropathy, for example, tend to faint on won’t increase pressure by much. But is standing up suddenly. They have problems plasma volume depletion a likely explana- with nerve conduction. tion here --considering his blood pres- sure?” Kay: “Like in patients with diabetes?” Kay: “No --he was not in shock --not Doc: “Yes --diabetic neuropathy is a quite with a systolic pressure of 160 mmHg common cause of orthostatic hypoten- and with the strong pulse that he had.” sion.” Doc: “His strong pulse is called a Corrigan Kay: “How about medicines?” pulse or a water-hammer pulse. It was due to his high .” Doc: “Yes --patients receiving medicines for --quite common --espe- Kay: “You mean the large difference be- cially alpha-1-adrenergic blockers.” tween his systolic and diastolic blood

Kay: “I did an internship on a psychiatric pressure?” ward. Many of the antipsychotic medi- Doc: “Yes, it was quite large because of cines do this also.” his great .”

Doc: “Not uncommon side effect of medi- Kay: “It’s as if he were exercising and all cines. But we did ask his daughter if he that blood was going to his muscles. had diabetes or was taking any medicines But it wasn’t. So why did he have such for hypertension or for his PTSD from the large stroke volumes?” Korean War, and she said “No”.” Doc: “Well --you listened to his heart. Kay: “But what if he was dehydrated or What did you hear?” bleeding internally or had diarrhea or

14 Kay: “I heard --with your help --an early flow among other properties of blood, decrescendo diastolic murmur and a lit- such as viscosity and density.” tle pre-systolic sound, which you said Kay: “Okay, so this murmur indicates was called an Austin Flint murmur. But that blood flows backwards across his what do these murmurs have to do with aortic valve?” his large stroke volume?” Doc: “Yes -- and his left , there- Doc: “He has aortic insufficiency. His aor- fore, fills during from two sides -- tic valve doesn’t close properly, so blood blood coming through the mitral valve as regurgitates back into his left ventricle dur- usual and blood flowing backwards ing diastole. This produces the decre- through an incompetent aortic valve.” scendo murmur right after the second heart sound.” Kay: “And this resulted in a large end- diastolic volume which produced the Kay: “The murmur did get louder as he large stroke volume and the large pulse leaned forward and exhaled.” pressure.” Doc: “Yes, that brought his heart closer to Doc: “Right.” your stethoscope. Still, it’s difficult to hear this murmur. Diastolic murmurs aren’t as Kay: “The other murmur, the pre- loud as systolic murmurs.” systolic one, must have been due to mi- Kay: “Why is this?” tral stenosis. Right?”

Doc: “Higher velocity of flow during sys- Doc: “Sort of, but his mitral valve is not tole. More turbulence. Higher Reynold’s really damaged as, for example, in rheu- matic fever. Here we have a functional number.” murmur.” Kay: “Higher what?” Kay: “A flow murmur?” Doc: “Reynold’s number --a way of esti- Doc: “Well, what happens is this. One of mating when turbulence is likely to occur. the leaflets of the mitral valve can’t open This is a dimensionless number which properly because it is kept partially shut by takes into account the velocity of blood

15 a jet of blood flowing backwards through Doc: “Yes --wet crackles from pulmonary the damaged aortic valve. So when the edema. Why were his lungs wet?” left atrium contracts toward the end of di- astole blood ejected through the mitral Kay: “Blood was backing up into his valve becomes turbulent and creates the lungs because his left ventricle couldn’t pre-systolic murmur, the so-called Austin handle the load?” Flint murmur.” Doc: “Blood wasn’t really backing up, but Kay: “His left ventricle is working hard a higher pressure was required to fill his left ventricle because it was hypertrophied --has been for a long time --and now it and stiff.” is hypertrophied. Right?”

Kay: “So more blood was filtered across Doc: “How do you know that it is hypertro- phied?” the capillaries in the lungs because cap- illary pressure was increased?” Kay: “Because the S-wave in lead V1 Doc: “Yes --and the lymphatics couldn’t plus the R-wave in V5 is greater than 35 quite handle the increased load. Couldn’t mm. --- You taught me that the other return all the extra fluid around his alveoli day. But I don’t understand why the ST back to the circulation.” segment is depressed in lead V5.” Kay: “I asked him if he got short of Doc: “Left ventricular strain --sloping of breath when he lies down, and he said the ST segment --indicates endocardial “Yes”. And he said that he slept with ischemia.” his head on three pillows.” Kay: “Is his left ventricle failing?” Doc: “Why did he use several pillows?” Doc: “Well, what do you think? What did you hear when you listened to his lungs?” Kay: “I know, this is called orthopnea and it is due to the edema fluid in his Kay: “His lungs didn’t sound normal. legs moving back into his lungs at Where those wet rales I heard?” night.”

16 Doc: “And also, when he lies flat more of Doc: “Yes --to move fluid from his lungs his lungs are below the level of the tricus- back into his feet.” pid valve. So hydrostatic pressure is higher in more lung capillaries than usual Kay: “And he also said that he can’t and more fluid is filtered into the interstitial make it all the way up the stairs to his spaces around the alveoli.” bedroom without having to stop several times because he runs out of breath.” Kay: “So more of his lung is under wa- ter?” Doc: “Yes, he has dyspnea on exertion or DOE for short.” Doc: “Yes, so-to-speak.” Kay: “Doc, I noticed that the residents in Kay: “He also said that he has asthma the hospital tend to speak in abbrevia- attacks at night which adds to his prob- tions and broken sentences to one- lem with breathing. But I didn’t hear any another, why is this?” wheezing when I listened to his lungs.” Doc: “They are usually in a rush and sort of Doc: “He has cardiac asthma which is dif- know how to complete a sentence started ferent from regular asthma.” by one of their colleagues without it being vocalized. A lot of medicine is repetition.” Kay: “How so?” Kay: “Alright, so what’s with Mr. Bach’s Doc: “In cardiac asthma it is edema fluid DOE?” that wells up from the alveoli into the bron- chioles distending their walls and imped- Doc: “When he gets ready to climb the ing air flow. This shortness of breath that stairs, his pre-motor cortex sends im- comes on at night is called paroxysmal over several pathways all the way nocturnal dyspnea or PND for short.” down to the muscles in his legs that are go- ing to do the work. Arterioles dilate and as Kay: “He said that these attacks were so muscle start to contract pre-capillary bad sometimes that he had to sit up sphincters click open in response to meta- with his legs dangling over the side of bolic by-products such as carbon dioxide the bed.” and adenosine that are released from cells. And his leg muscles get warm from the

17 heat generated from the brake down of Kay: “He feels short of breath --is dysp- ATP molecules and this along with release neic -- because he is not getting of endothelial relaxing factors dilates ves- enough oxygen. Right?” sels even more. These mechanisms fur- nish Mr. Bach’s leg muscles with the oxy- Doc: “You might think so because he is, in- gen and nutrients needed to climb the deed, not getting enough oxygen. But air- steps.” hunger --or not being able to catch ones breath -- is due to the excessive work that Kay: “Okay, Doc --got it. What next?” his inspiratory muscles have to do to dis- tend his alveoli which have become stiffer Doc: “Now all this extra blood that rushes because of the surrounding edema fluid. It to his leg muscles in arteries comes back is this extra work that gives him the sensa- out in his veins and is returned to the right tion of dyspnea. It’s a subjective feeling ventricle which pumps more into his --a little bit like pain.” lungs.” Kay: “That’s interesting. Now I also no- Kay: “Well, that happens to all of us ticed that his neck veins were dis- when we exercise. So what is different tended. I guess this means that his with Mr. Bach?” right ventricle was also failing. But Doc: “You have a normal cardiac reserve, why? It wasn’t working overtime like where your left ventricle pumps about 5 his left ventricle?” liters/minute at rest, but on exercising can Doc: “Kay, but it was. It was also working pump perhaps 15 liters/minute or more. much harder because left ventricular fail- But Mr. Bach does not have much of a car- ure invariably leads eventually to right diac reserve. His heart can pump just .” about enough blood to get by at rest.”

Kay: “Why is that?” Kay: “And so the blood that is not pumped by the left ventricle is left in Doc: “When the left ventricle fails and fluid the lungs and takes his breath away?” accumulates in the lungs, the amount of oxygen in blood decreases and this Doc: “Yes --he becomes dyspneic. Hence causes arterioles in the lung to constrict.” the term dyspnea on exertion.”

18 Kay: “But I thought blood vessels re- muscle that behave in some respects simi- laxed when oxygen is lacking. Isn’t this lar to hemoglobin in that they change their how more blood flows to tissues that conformation depending on the amount of need it? Remember, “” oxygen bound to them.” we talked about yesterday?” Kay: “And this conformational change Doc: “Big difference between autoregula- with little oxygen around causes the tion in peripheral tissues and in the lung. contraction?” In the lung a decrease in oxygen tension Doc: “Eventually, yes --but first the confor- causes constriction of blood vessels, not mational change in the protein closes a po- relaxation.” tassium channel so that potassium diffu- Kay: “But why?” sion out off the smooth muscle cell is slowed.” Doc: “ If a section of the lung is not getting oxygen because a bronchus is plugged Kay: “And that moves the membrane po- with mucus, you don’t want to have blood tential away from the potassium equilib- flowing to that section of lung. It won’t rium potential of -90 mV. Right? We pick up any oxygen or get rid of any car- learned about the Nernst Equation and bon dioxide. In fact, blood flowing through membrane potentials not long ago in an unventilated section of lung is like a class.” right-to-left shunt -- allowing unoxygen- ated venous blood to flow straight into the Doc: “Good, Kay --the membrane poten- arterial circulation as if you had poked a tial becomes less negative at which point a hole in the interventricular septum. So no, voltage-gated calcium channel in the mem- the response to hypoxia is reversed in the brane opens and calcium ions flood the lung.” cell and make it contract.”

Kay: “But how do blood vessels in the Kay: “And this increases the resistance lung sense that oxygen is low and that against which the right ventricle has to they ought to constrict?” eject its stroke volume?”

Doc: “There are receptor proteins in the membranes of pulmonary vascular smooth

19 Doc: “ Yes -- pulmonary resistance, that is Doc: “Not quite. In a sphere, like an alveo- the on the right ventricle, in- lus or ventricle, it’s twice the radius. But creases and it eventually fails.” you’re right, wall tension will be increased so that more ATP molecules and more oxy- Kay: “What do you mean by “fails”?” gen and more coronary blood flow will be needed to force the blood out. Nothing is Doc: “Fails to ejected 2/3rds of its end- for free.” diastolic volume.” Kay: “But doesn’t the ventricle eventu- Kay: “So his right ventricle is not con- ally hypertrophy?” tracting fast enough?” Doc: ”Yes, it does, and with hypertrophy Doc: “Yes, not fast enough in the time it wall tension is distributed over more sar- has to contract during .” comeres. This decreases overall wall ten- Kay: “So what happens?” sion. But now the ventricle becomes stiffer -- more difficult to fill.” Doc: “It increases its end-diastolic vol- ume.” Kay: “So his CVP has to go up?”

Kay: “A bigger heart?” Doc: “Yes --his neck veins should have been filled to no more than about 8 cm Doc: “Yes --the ventricular chamber dis- above his sternum.” tends and with the help of the Frank- Starling mechanism manages to eject a Kay: “That’s because the tricuspid valve bigger stroke volume.” is zero and it is about 5 cm below the sternum?” Kay: “But that requires more energy and more work. Doesn’t it?” Doc: “Right. Total pressure about 13 cm H2O or roughly 10 mmHg.” Doc: “Yes, it’s inefficient because of the LaPlace equation.” Kay: “Specific gravity of mercury is about 13?” Kay: “I remember: Wall tension equals pressure times radius. Doc: “Yes, Kay, if I remember correctly.”

20 Kay: “So blood then started flowing Doc: “As edema fluid distends the intersti- backwards into his legs causing his tial spaces, elastic tissues in these spaces edema?” are stretched and create a back-pressure which eventually stops more fluid from en- Doc: “No --blood keeps flowing toward the tering this compartment.” heart even when the CVP is high. The only difference is that a higher pressure is now Kay: “But won’t his plasma volume be required in foot capillaries to keep blood depleted by the amount of extra fluid moving upwards to the heart.” ending up in his feet and legs?”

Kay: “Doc, that’s what I’m saying. Blood Doc: “His plasma volume is kept at a near flows backwards into the feet to raise normal level by his kidneys.” pressure to keep blood moving.” Kay: “How do his kidneys do that?” Doc: “No --nothing flows backwards. Doc: “As fluid is lost to interstitial spaces, There are one-way valves in the large veins less blood is returned to the right atrium that keep that from happening. No -- where low pressure baroreceptors in the blood stays in the feet. Won’t move until subendocardium sense the decrease in enough has accumulated to generate the .” recoil pressure required to move blood against gravity up to the heart.” Kay: “Plasma volume receptors?”

Kay: “And the increase in capillary pres- Doc: “Yes --but the body can’t measure sure then causes more fluid to be fil- blood volume, it only has sensors for pres- tered into the interstitial spaces of Mr. sure. But these low pressure receptors in Bach’s feet --creating edema?” effect measure volume. You are right.”

Doc: “Yes --that is, if the lymphatics are Kay: “So these volume receptors send overwhelmed and can’t keep up with the impulses to the vasomotor center which influx.” increases sympathetic outflow to the kidney?” Kay: “What keeps his feet and legs from getting bigger and bigger from all that fluid?”

21 Doc: “Yes --and sympathetic nerves con- transporters to move them back into blood strict both the afferent and efferent arteri- in the proximal tubule.” oles of glomeruli in his kidneys.” Kay: “You mean like the transporters for Kay: “Why not just clamp down on the glucose and amino acids that are fil- afferent arteriole to decrease filtration tered and reabsorbed in the proximal tu- at the glomeruli and minimize loss of flu- bule?” ids in the urine?” Doc: “Yes --potentially toxic substances Doc: “By clamping down on the efferent that have been digested and absorbed into arteriole as well, you increase the filtration blood in the gut are filtered in the glomeruli fraction, which enhances salt and water re- and because these foreign substances absorption in the proximal tubule.” don’t have transporters in the proximal tu- bule are left behind in tubular fluid and are Kay: “We had this in class: The filtration excreted in a smaller than usual volume of fraction is equal to the glomerular filtra- urine.” tion rate divided by renal plasma flow. Right?” Kay: “So you are saying that when the kidney is not getting its usual share of Doc: “Yes, Kay --so if you clamp down on blood it still tries its best to get rid of both the afferent and the efferent arteriole wastes.” --that is increase two resistances in series --the filtration fraction increases more than Doc: “Yes, Kay --that’s the idea. That is if you had only constricted the afferent arte- why the kidney has these two resistances riole.” in series in the glomeruli. A clever way of making it do its job more efficiently with a Kay: “Got it Doc. But why? Why filter lower rate of glomerular filtration. It’s not relatively more plasma fluid only to reab- just sympathetic stimulation that increases sorb it again in the proximal tubule. the filtration fraction, but also hormones Seems like a waste of energy.” such as II and epinephrine.”

Doc: “But that’s how the kidney can still Kay: “If the glomerular filtration rate is get rid of waste products that are filtered decreased, the concentration of urea and --unlike salts-- do not have special

22 and creatinine in blood will increase. where both BUN and creatinine rise propor- Won’t it, Doc?” tionally in blood.”

Doc: “Yes, if there is a significant decrease Kay: “So do you think Mr. Bach has pre- in renal or if there has been dam- renal azotemia because his heart is fail- age to the glomeruli. That is how we can ing?” tell that kidney function is reduced. But if function is reduced because of decreased Doc: “No, not at this time. Although we perfusion, the concentration of urea will don’t know for sure without analyzing a rise more than the concentration of creati- blood sample for urea and creatinine. He nine. That is, the ratio of BUN/creatinine has presumably compensated for the de- will increase. creased blood flow to his kidneys by retain- ing more salt and water and raising his car- Kay: “Is that important?” diac output back to normal -- at least while he is resting. So his renal blood flow is Doc: “That is how we can distinguish a re- now normal.” versible from an irreversible decrease in glomerular filtration due to destruction and Kay: “So it is only intermittently that his loss of glomeruli.” kidney go into this salt and water retain- ing state?” Kay: “I don’t understand why the con- centration of urea rises more than the Doc: “Yes, especially during the day when concentration of creatinine with de- gravity causes blood to pool in his legs. creased renal blood flow.” That’s when he retains more salt and wa- ter. Doc: “Creatinine is filtered by the glomeruli and never reabsorbed by the nephron. By Kay: “From the proximal tubule because contrast, urea is filtered but also reab- of the increased filtration fraction?” sorbed from tubular fluid --more so when the kidney is underperfused. Therefore, a Doc: “Yes, and from the collecting ducts rise in the BUN/creatinine ratio in blood is because of vasopressin and aldosterone.” called pre-renal azotemia to distinguish Kay: “Is this because more vasopressin this reversible cause of diminished kidney and aldosterone are released into the function from irreversible loss of glomeruli

23 circulation when low pressure barore- Kay: “Yes, Doc. We learned that noc- ceptors in the atria are stretched less turia is a common symptom in patients than usual?” with congestive heart failure.”

Doc: “Yes --and even much more so Doc: “It probably helps Mr. Bach breathe a should high pressure baroreceptors in the little easier than if this fluid ends up in his carotid sinuses sense a drop in blood pres- lungs at night.” sure as they did, for example, when Mr. Bach stood up and fainted.” Kay: “Doc, his legs and feet looked aw- ful. The swelling, the discoloration, no Kay: “So Mr. Bach collects extra salt and hair, and the ulcer.” water as he walks around during the day and deposits it in his feet and legs Doc: “True, this is from stasis dermatitis. as edema, and then at night gets rid of Edema increases the diffusion path for oxy- gen and nutrients -- a greater distance be- it again?” tween capillaries and skin. Hair no longer Doc: ”Yes --at night when this fluid leaves grows. Red cells burst leaving behind iron the legs and enters the circulation, the vol- deposits which stain his skin.” ume receptors in the atria are stretched and they turn off vasopressin and aldoster- Kay: “And that ulcer on his ankle is not one secretion.” going to heal unless he takes care of himself.” Kay: “Is that why Mr. Bach said that he couldn’t sleep because he had to go to Doc: “You are right. He has to keep the leg up high as much as possible to reduce the bathroom several times at night?” the swelling.” Doc: “Yes he had nocturia --not only from Kay: “But he has no feeling in his feet. lack of vasopressin and aldosterone but also because another hormone, the so- And he was also pretty unsteady. No called atrial natriuretic peptide. This hor- warning, no pain when he bumps into mone is released from atrial muscle cells things and gets an abrasion or a cut when they are stretched and it increases which will then go unnoticed and fester. salt excretion by the kidney.” Why is this, Doc? Why can’t he feel his feet?”

24 Doc: “He probably has peripheral neuritis he had also acquired. That is why he and perhaps something more serious that should have been tested with the VDRL is interfering not only with pain sensation test for syphilis, which was not done at the but also with balance and his position time. And so his condition quietly pro- sense.” gressed to the final stage of tertiary syphi- lis, which is causing him problems now -- Kay: “Could peripheral neuritis be re- decades later.” sponsible for his orthostatic hypoten- sion?” Kay: “How do we know that he has terti- ary syphilis without the VDRL test?” Doc: “Possibly.” Doc: “He has the Argyll-Robertson pupil Kay: “Embarrassing -- when you asked which is almost diagnostic for syphilis.” this nice old man if he had syphilis.” Kay: “You tested for that when you al- Doc: “Yes, Kay --taking a sexual history is most poked him in the eye?” awkward -- but important.” Doc: “Yes, his pupils were small, and they Kay: “And when he started reminiscing constricted to an even smaller size when I about the girls in Munich a long time moved my finger towards his nose. That’s ago.” expected --a normal accommodation re- sponse. But they did not constrict when I Doc: “Kay, it’s sometimes difficult not to ap- was shining a light into his eyes. That’s ab- pear impatient when taking a history. But normal. That’s the Argyll-Robertson pu- you have to be polite while keeping your pil.” patient focussed on what is essential to making a diagnosis.” Kay: “Why did he have aortic insuffi- ciency?” Kay: “Well, he admitted to having had gonorrhea, but he said nothing about Doc: “Syphilis is caused by treponema syphilis.” pallidum -- a spirochete, a little worm-like organism -- that gets into the vasa va- Doc: “His treatment for gonorrhea masked sorum of the ascending aorta.” the more serious venereal disease which

25 Kay: “You mean the little blood vessels Doc: “Right --that’s what one fears may that supply the tissues in the wall of the happen with aneurisms. But before this aorta?” happens the aneurism stretches the aortic valve so that the leaflets no longer close Doc: “Yes --and these little vessels get tightly during diastole. Hence the back- clogged up by the spirochete, so the wall leak of blood which you heard as an early of the aorta doesn’t get the nutrients it diastolic decrescendo murmur.” needs and is weakened. “ Kay: “So what are they going to do for Kay: “Yes, but what does that have to do him?” with a leaky aortic valve?” Doc: “He needs a thorough workup by a Doc: “I’m coming to that. The weakened cardiologist and a neurologist, including wall of the ascending aorta bulges a little. the VDRL test, which he didn’t get several This increases it’s radius. As the radius in- decades ago in the Army -- and a spinal creases, so does wall tension.” tap to examine his cerebrospinal fluid.”

Kay: “Oh, I know -- the Laplace equa- Kay: “And he needs a new aortic valve tion again, but now in a blood vessel and penicillin shots.” where wall tension equals pressure times the radius. So an increase in the Doc: “A new valve, yes, but no penicillin radius of the aorta will increase its wall --remember he is allergic to it. So they will give him something else, like doxycycline tension?” perhaps.” Doc: “And as wall tension increases, a few more fibers in the wall rupture and the Kay: “The neurologist can also see aorta bulges a little more. And this, in turn, what’s happening with his balance. He increases tension which ruptures more fi- didn’t know if his big toe was up or bers and so forth.” down when you moved it and he had his his eyes closed. Kay: “Like a weak spot in a tire --usually ends in a blow-out?” Doc: “And he didn’t have a knee jerk or vi- bration sense either.”

26 Kay: “No he couldn’t feel the vibrations Kay: “See you tomorrow.” of your tuning fork. What does that Doc: “Good night, Kay.” mean?”

Doc: “No proprioception, no position sense! And he also had a positive Rom- berg’s sign.”

Kay: “That’s when he couldn’t keep his balance with his eyes closed and feet to- gether?”

Doc: “Yes, he had a broad leg stance be- cause the nerves in the dorsal column of his spinal cord have probably lost their in- sulation --are demyelinated.”

Kay: “But why did he have to close his eyes.”

Doc: “Sight may compensate for the loss of proprioception in his feet. That’s why you have to test for balance with closed eyes. He has tabes dorsalis --one of the many complications of latent syphilis.”

Kay: “An awful disease. Good that we can now treat it with antibiotics.”

Doc: “--if we catch it early.”

Kay: “I feel sorry for him.”

Doc: “I do too.”

27 2

Regulation of Cardiac Output Regulation of Cardiac Output

Lecture 3-1: Regulation of Cardiac Output

29 This section examines how left and right ventricular output are regulated by end- diastolic filling volume, myocardial contrac- tility, and .

1. Effect of CVP and PAWP on Right and Left Ventricular Output

Cardiac output by the right or left ventri- cles is equal to ventricular stroke volume times heart rate (CO = SV x HR). Because stroke volume increases as a function of end-diastolic volume (Frank-Starling phe- nomenon), and end-diastolic volume is pro- Fig. 8-4. Cardiac Function Curves. Cardiac portional to CVP (right ventricle) or PAWP output of the right or left ventricles has been (left ventricle), cardiac output also in- plotted as a function of the (CVP) or wedge creases as a function of CVP or PAWP pressure (PAWP), respectively. The cardiac (Fig. 8-4, normal function curve at rest). Be- output curve is shifted upward in conditions cause cardiac output also changes as a that increase and (or) heart rate, provided that the increase in function of heart rate and myocardial con- heart rate is not excessive or prolonged. The tractility at any end-diastolic filling volume, cardiac output curve is shifted downward in the normal (resting) conditions that decrease myocardial contrac- tility and (or) heart rate. is shifted upward when the heart is con- tracting more powerfully and/or more rap- idly. The normal function curve is shifted downward when myocardial contractility is ing) cardiac function curve include: para- depressed and/or heart rate is abnor- sympathetic stimulation (causing sino- mally slow. Conditions that raise the nor- atrial and atrio-nodal conduction blocks), mal (resting) cardiac function curve in- beta-1-adrenergic antagonists, calcium clude: sympathetic stimulation, beta-1- channel blockers, myocardial infarction, adrenergic agonists, or cardiac glycosides. valvular heart disease, atrial fibrillation, or Conditions that decrease the normal (rest- acidosis. It is important to bear in mind

30 that an increase in heart rate will only in- is diseased or its normal function (contrac- crease cardiac output up to a point, which tility or heart rate) is otherwise depressed, depends (among other factors) upon the cardiac output is limited not by venous re- level of conditioning and the duration of turn but by the pumping capability of the the tachycardia. Indeed, in patients with right and left ventricles. atrial fibrillation or hypertension decreasing heart rate below 100 beats/min or decreas- ing the afterload by reducing blood pres- sure will shift the cardiac function curve up- ward.

We will return to these various function curves a little later. For now let's focus on the normal (resting) curve. At rest, cardiac output is about 5 liters/min and the CVP is about 5 mmHg and the PAWP about 10 mm Hg. According to the normal cardiac function curve in Figure 8-4, when CVP and PAWP double cardiac output in- creases almost two and one-half times.

So why does the heart actually pump about 5 liters/min instead of 12 liters/min? Only 5 liters of blood are returned to the heart each minute, and the heart cannot pump more blood than is being delivered to it. If venous return were 12 liters/min, then the heart would pump 12 liters/min and do so without any additional stimula- tion (the heart would not have to shift to a higher function curve). In other words, ve- nous return regulates cardiac output for a normally functioning heart. When the heart

31 3

Regulation of Venous Return Effect of Peripheral Resistance on Cardiac Output

Lecture 3-2: Effect of Peripheral Resistance on Cardiac Output

33 The amount of blood that flows into the Thus, in the normal heart, venous return de- central veins and generates the filling pres- termines cardiac output. sure of the right ventricle (and subse- quently [via the PAWP] of the left ventricle) 1. Increased Venous Return will depend upon the amount of blood that (and Cardiac Output) with flows from the capillary beds of the various Shunts and Altered Meta- organs and tissues of the body. Blood flow bolic States through these capillary beds depends, in Venous return and cardiac output are nor- turn, upon the various autoregulatory mally regulated by the metabolic needs mechanisms that allow blood to enter or- and functions of the various organs and tis- gans and tissues. Thus, when tissues need sues that make up the body. There are more blood to meet their metabolic needs, times, however, when blood flow through vasodilator substances accumulate and tissues is excessive, for example when tis- cause pre-capillary sphincters and metarte- sue metabolism is abnormally increased rioles to relax. As more blood flows to tis- (e.g., hyperthyroidism) or when blood is by- sues and organs, more is returned to the passing capillary beds altogether by flow- heart and cardiac output increases, accord- ing via low resistance shunts between ar- ingly. Therefore, cardiac output is regu- teries and veins (e.g., Paget's disease). In lated by the sum of the individual meta- both instances, the total peripheral resis- bolic needs of the tissues. When more tance is decreased without changing the blood is needed, for instance, with exer- compliance of the capacitance vessels re- cise, skeletal muscle will take a larger frac- sponsible for conducting blood back to the tion of the cardiac output, which it will rap- heart. This increase in venous return re- idly return via low resistance channels to sults in increased cardiac output. the veins. The CVP will increase and fill the right ventricle more, so the right ventricle Let us illustrate this with a simulation (Fig. will pump more blood into the pulmonary 8-5) of experiments carried out by Guyton artery. The PAWP, in turn, will increase and and colleagues on anesthetized dogs. fill the left ventricle more, so that the left Catheters are inserted into a femoral artery ventricle will pump more blood into the and vein, and the ends are connected by a aorta, from where the increased cardiac three-way stopcock. When the stopcock is output is delivered to exercising muscles. closed, only 5 L/min of blood flows

34 ceptor reflex, resulting in movement of flu-

ids from the interstitium to blood and reten- tion of salt and water by the kidneys. By this regulatory mechanism, blood flow to tissues is soon reestablished. With the ad- ditional 5 L/min of blood flowing directly from the femoral artery into the femoral vein, venous return will increase to 10 L/ min. The cardiac output will now increase to 10 L/min, not from sympathetic stimula- tion, but simply from the increase in the end-diastolic ventricular volume that in- creases the stroke volume by the Frank- Fig.8-5. Effect of an Arterio-Venous Shunt on Venous Return and Cardiac Output. A shunt Starling mechanism. This experiment illus- was created between the femoral artery and trates that cardiac output is regulated by vein in an anesthetized dog, and blood flow venous return. through the shunt was regulated by a stop- cock. When the stopcock was closed, venous There are a number of conditions that are return and cardiac output was 5 L/min. When the stopcock was opened, 5 L/min of blood characterized by an increase in cardiac out- flowed through the shunt to the femoral vein, put where the high cardiac output state which was added to the 5 L/min of blood al- can be ascribed to a primary decrease in ready returning to the heart from various or- gans and tissues. Venous return and cardiac the total peripheral resistance (without a output were thereby increased to 10 L/min. change in venous compliance). This is seen, for example, in patients with Paget's disease, where extensive arterio-venous through capillary beds of various organs fistulae are formed in bone. Also, during and tissues and is returned to the heart. the third trimester of pregnancy venous re- When the stopcock is first opened, 5 L/min turn and cardiac output increase markedly of blood flows through the shunt and none as blood is shunted through low resis- through the tissues. The sudden drop in to- tance pathways in the placenta. For this tal peripheral resistance causes a fall in reason, young women with rheumatic val- blood pressure, which activates the barore- vular heart disease may not be aware of their cardiac disability until they develop

35 signs and symptoms of congestive heart a decrease in sympathetic outflow to the failure in the late stages of pregnancy. Hy- vascular system - cardiac output de- perthyroidism also is often associated creases because blood pools in the veins with an increased cardiac output, partly be- and is not returned to the heart. cause the heart is stimulated to contract more and tissues and is returned to the 2. Effect of Gravity on Ve- heart. When the forcefully, partly because nous Return (and Cardiac an increase in tissue metabolism leads to Output) enhanced blood flow through capillary Gravity is an important factor in venous re- beds. Marked peripheral is turn (Fig. 8-6). Blood in veins below the seen in beriberi (thiamine deficiency), level of the heart is subjected to gravity, when glucose metabolism cannot proceed which pulls on the column of blood, dis- normally. This condition causes high car- tending vessels below the heart. Just look diac output states and high output cardiac at the veins in your hand, when your arm is failure when the heart cannot keep up with relaxed and hanging down by your side. the high venous return. (The heart also con- Now raise your arm and watch the veins in tracts less forcefully than normal in beri- your hand collapse as it passes the level of beri.) We have already seen that severe your heart. The veins above the heart, anemia in the man in case 6 can lead to such as those in the neck, are normally col- an increase in cardiac output. In this situa- lapsed when a person is sitting or stand- tion cardiac output increases as tissues de- ing. As blood flows with gravity from the prived of oxygen vasodilate and return head to the chest, it creates a partial vac- more blood to the heart. uum in the venous sinuses of the cranium that tends to siphon blood from arteries It must be emphasized that a decrease in into brain capillaries. The neurosurgeon total peripheral resistance (e.g., by relaxa- must be aware of this when operating on a tion of arteriolar smooth muscle) will only patient in the sitting position. If a vein in lead to an increase in venous return and in the head or neck is cut, air may be sucked cardiac output, provided that venous com- into the heart, resulting in an air embolus. pliance is not also increased (e.g., by re- laxation of venous smooth muscle). When both arterioles and veins relax simultane- ously - as occurs in neurogenic shock with

36 3. Importance of Venous- Compliance, Valves, and Skeletal Muscle in Facilitat- ing Venous Return (and Car- diac Output)

The tendency for gravity to cause pooling of blood in the legs is counteracted in three major ways:

(1) Pooling of blood in the extremities upon sudden standing minimized by the barore- ceptor reflex, which increases sympathetic outflow to the smooth muscle of veins, de- Fig. 8-6. Effect of Gravity on Venous Pressure (A) The hydrostatic pressure of blood due to creasing their compliance. gravity for a person standing quietly is shown to be a positive value in veins below the heart (2) The major veins have one-way valves and a negative value in veins above the heart. pointing toward the heart. These valves, Accordingly, in a foot vein 80 cm below the when competent, break up the long col- heart pressure will equal +80 cm of water, whereas in a hand held 40 cm above the heart, umn of blood between heart and feet into venous pressure will equal -40 cm of water. (B) smaller sections, so that the hydrostatic Venous pressures at the ankle are compared pressure is felt only over the distance be- for a person lying, standing quietly, or running. Note that during running skeletal muscle con- tween any two valves. This is not true, how- traction squeezes veins, which pumps blood ever, when valves become incompetent. from the ankle against the force of gravity to- Then the full effect of gravity is transmitted ward the heart. to the walls and the veins bulge and be- come tortuous. This is particularly true for superficial veins, such as the saphenous veins are squeezed and blood is milked veins in the legs, which lack support from from one valve past the next toward the surrounding musculature. Such incompe- heart. Lack of muscle contraction - as for tent veins are called varicose veins. soldiers standing at attention - may lead to peripheral venous pooling and fainting, es- (3) Most deep veins are surrounded by pecially in hot weather. skeletal muscle, and as muscles contract,

37 4. Importance of Inspiration on Venous Return (and Car- A Inspiration Chest wall diac Output) 4 5 Negative intrathoracic Pulmonic valve closure pressure distends delayed (physiologic pulmonary vessels and splitting of second heart decreases venous return Lung sound) Another important factor aiding venous re- to the left atrium turn is inspiration (Fig. 8-7). During inspira- 3 Negative intrathoracic pressure sucks venous tion the intrapleural (or intrathoracic) pres- blood into right atrium sure drops, becoming more subatmos- Negative pressure Arteries Diaphragm pheric and causing distention of the large Veins Positive pressure 1 vessels in the chest. This tends to suck 2 Downward movement of diaphragm on Positive intra-abdominal inspiration increases pressure forces blood in intra-abdominal pressure more blood into the right atrium. Because vena cava toward right Tissues atrium the downward movement of the dia- Capillaries phragm increases intra-abdominal pres- B Inspiration Expiration Intrathoracic pressure Decreased Increased sure, vessels in the abdominal cavity are Right ventricular stroke volume Increased Decreased Thoracic blood volume Increased Decreased compressed, which simultaneously forces Left ventricular stroke volume Decreased Increased

Fig. 8-7. P. Eggena, blood toward the heart. It is noteworthy The Physiological Basis of Primary Care, Novateur Medmedia Fig. 8-7. Effects of Respiration on Venous Re- that some patients in hemorrhagic shock, turn and Cardiac Output. (A) The sequence of who suffer from a decreased venous re- events (1) thru (5) occur during inspiration. (B) turn, are found to have intense constriction Effects of inspiration and expiration on intratho- racic pressure, thoracic blood volume, and right of the abdominal muscles, which would or left ventricular stroke volumes are listed. tend to facilitate venous return.

While a deep inspiration increases venous the lungs, so less flows into the left ventri- return to the right ventricle, left ventricular cle, and, therefore, the left ventricular filling and cardiac output actually de- stroke volume is diminished (Fig. 8-7). crease. Indeed, this is why the second heart sound is split on inspiration (physio- As more blood enters the right atrium on logical splitting of S2). Only on expiration inspiration, the rhythm of the heart be- does the extra blood (returned to the heart comes irregular (sinus arrhythmia) due to during the deep inspiration) increase left a brief increase in the rate of depolariza- ventricular output. The reason is that dis- tion of the SA node. This is partly caused tention of pulmonary vessels on inspiration by stretching of SA nodal tissues and allows more blood to pool (temporarily) in partly by stimulation of the SA node by the

38 Bainbridge reflex. This reflex is initiated life is not divided into inspiration and expi- when the atrium is stretched. Afferent im- ration but that there are relatively long peri- pulses are carried over vagal fibers to the ods of time between breathing in or out. It medulla and result in decreased parasym- is in these long intervals between breaths pathetic and increased sympathetic stimu- that intrathoracic pressure is normally lation of the SA node and atrial muscle. slightly subatmospheric (e.g.,-2 mmHg). This reflex moves blood out of the atrium This is also true for patients on positive and into the ventricle. pressure ventilators, unless the ventilator has been set for continuous positive air- While inspiration facilitates venous return way pressure (CPAP). to the heart, an increased (positive) intra- thoracic pressure during a forced expira- Important changes in venous return, car- tion impedes venous return. This is why a diac output, and blood pressure are ob- trumpet player has a red face and dis- served in breathholding and straining dur- tended neck veins. Blood will not drain ing the (Fig.8-8). Dur- from the neck and face into the right ing the Valsalva maneuver, a person takes atrium as long as these structures are com- in a deep breath, then exhales forcefully pressed. This is, in part, why patients with against a closed glottis. This may increase prolonged and repeated coughing spells intrathoracic pressure, for example, from may faint. The continued positive intratho- -2 to +40 mmHg. Because the aorta and racic pressure during the coughing epi- large arteries in the chest are exposed to sodes prevents venous return and dimin- this additional 42 mmHg, blood pressure in ishes cardiac output. Patients on positive the brachial artery rises by an extra 42 pressure ventilators, especially when the mmHg and then falls gradually, as venous ventilator is set for PEEP (i.e., positive return to the right and left ventricles de- end-expiratory pressure), experience a clines and cardiac output decreases. The decrease in venous return and in cardiac decrease in blood pressure initiates the ba- output. It is, therefore, important to weigh roreceptor reflex, which causes heart rate the potential benefits of using PEEP (e.g., and peripheral to in- increased arterial oxygen tension of blood) crease. This results in a small increase in against a diminished cardiac output and blood pressure toward the end of the pe- decreased delivery of oxygenated blood to riod of straining, which is an inadequate tissues. We sometimes seem to forget that compensatory response. As the glottis sud-

39 as blood, waiting to enter the heart during

the straining phase, suddenly floods the ventricles and markedly increases cardiac output at a time when the total peripheral resistance is still high from the vasocon- strictor response initiated toward the end of the straining phase. The high blood pres- sure decreases heart rate (via the barore- ceptor reflex) and decreases peripheral re- sistance with the result that blood pressure slowly returns to its pre-straining level.

The Valvsalva maneuver (with adequate blood pressure monitoring as in Figure 8-8) is useful in testing the responsiveness of the baroreceptor reflex (and the ). However, for certain pa- Fig. 8-8. The Valsalva Maneuver. Intrathoracic pressure (A), mean blood pressure (B), and tients, such as those with a recent myocar- heart rate (C) are recorded before, during, and dial infarction, the Valsalva maneuver after the straining phase of the Valsalva maneu- places an inordinate strain on the heart ver. At the first arrow (start) the subject breathes in deeply and then expires forcefully and should be avoided. against a closed glottis. At the second arrow (stop) the subject opens the glottis and relaxes the abdominal muscles.

denly opens and the diaphragm relaxes, in- trathoracic pressure returns to normal (i.e., -2 mm Hg), and brachial artery blood pres- sure falls precipitously. Within seconds, however, blood pressure and pulse rate shoot up to levels well beyond normal (i.e., the overshoot of the Valsalva maneuver)

40 Model of the Circulation

Lecture 3-3: Model of the Circulation

41 5. Effect of Plasma Volume by a series of ventricular escape beats on Venous Return (and Car- (note the large, wide QRS complexes). As diac Output) the heart stopped beating, the femoral ar- tery blood pressure decreased to a basal Finally, an important factor in regulating ve- value of approximately 10 mmHg (middle nous return is the extent to which the veins panel) and pulmonary artery pressure are filled with blood. It is not just the blood equilibrated at a similar level, i.e., at about volume that is important, but the relation- the level of the PAWP (top panel). These ship between the amount of blood and the observations indicated that, in the absence compliance of the veins (e.g., their sympa- of the heart's pumping action, blood sim- thetic tone), because it is ultimately the ve- ply flows down its pressure gradient from nous pressure that moves blood toward arteries into veins until all pressures in the the heart. This force, which is generated circulation are equal. This equilibrium pres- by veins as they contract around the vol- sure is called the mean circulatory filling ume of blood they hold, is sometimes re- pressure. In the experiment in Fig.8-9, the ferred to as vis a tergo. Also contributing mean circulatory filling pressure is about to this force is the pressure transmitted equal to the pulmonary artery wedge pres- through the capillaries by blood pumped sure, or about 10 mmHg (A). into arteries. Of course the volume of blood and the pressure in veins changes When the electrical stimulus was removed constantly as blood flows continuously from the vagus (B), systemic blood pres- into veins from capillaries on one end and sure returned over a period of five beats to is pumped out by the right ventricle on the normal (C). The sequence of events respon- other end. Therefore, the resting recoil sible for returning the dog's blood pres- pressures of veins and arteries can only be sure to normal is shown in human terms in measured when no blood is flowing, i.e., Figure 8-10. In this model of the peripheral when the heart has stopped. We observed circulation, we will assume that the periph- such resting recoil pressures upon stop- eral vascular resistance is 20 mmHg/L/ ping the heart in an anesthetized dog (Fig. min. 8-9). Stimulating the animal's right vagus with an electrical impulse caused sinus ar- During vagal stimulation at point A (Figs. rest (note the absence of P waves on the 8-9, 8-10), cardiac output was 0 L/min and ECG tracing in the bottom panel), followed systemic arterial and venous pressures

42 had equilibrated to a value of about 10 mmHg, i.e., the mean circulatory filling pressure (MCFP). When vagal stimulation was stopped (B), the heart resumed beat- ing. The first beat moved some blood from central veins into the aorta and large arter- ies, causing the CVP to drop from 10 mm Hg to 9 mmHg and systemic to rise from 10 mmHg to 29 mmHg. The greater increase in arterial pressure as compared to the fall in CVP for an equivalent blood volume change is ex- plained by the much lower compliance of arteries than veins. Although the left ventri- Fig. 8-9. Mean Systemic Filling Pressure cle ejects a certain stroke volume into the (MSFP). The right was stimulated in an anesthetized dog. ECG as well as pulmonary ar- aorta during the first beat (B), only part of tery pressure (with a Swan-Ganz catheter) and sys- this stroke volume moves through capillar- temic arterial pressure (with a catheter in the femo- ies and veins and is eventually returned to ral artery) were recorded simultaneously. Vagal the heart. The other portion of the stroke stimulation caused a sino-atrial block with an ideov- entricular escape rhythm. Note that systemic arte- volume was used to prime the arterial rial pressure fell to approximately 10 mmHg and pul- pump. In other words, the aorta and large monary artery pressure reached a level that was arteries had to be first stretched to a point close to the wedge pressure (PAWP) (A). When va- gal stimulation was stopped (B), systemic arterial where the recoil pressure was sufficient to pressure returned to pre-stimulation values within 5 move blood through a peripheral resis- heart beats (C). tance of 20 mmHg/L/min. We can calcu- late the amount of blood flow (the cardiac output) that occurred during the first two The cardiac output (CO) is equal to the dif- beats, where the average systemic mean ference between the mean systemic arte- arterial pressure was 29 mmHg and the rial pressure (MSAP) and central venous CVP 9 mmHg, in the following way: pressure (CVP) divided by the total periph- eral resistance (TPR, fixed at 20 mmHg/L/ CO = (MSAP -CVP)/TPR min). Accordingly, during the first two heart- beats (B):

43 CO = (29 - 9) mmHg/20 (mmHg/ L/min) = 1 L/min

In other words, when vagal stimulation was stopped, blood started to move around the circulation at a rate of 1 L/min during the first two heart beats.

Five heart beats later (C), enough blood had accumulated in the aorta and large ar- teries to increase the systemic mean arte- rial pressure to 105 mmHg, and the loss of blood from the central veins had reduced CVP to 5 mmHg. Now: Fig. 8-10. Model of the Circulation. The circula- CO= (105 - 5) mmHg/ 20 (mmHg/ L/ tory system is modeled after the experiment de- picted in Figure 8-9. Assuming a total periph- min) = 5 L/min eral resistance of 20 mmHg/L/min, cardiac out- put (CO) is 0 L/min (A) when the systemic In other words, once the large arteries had mean arterial pressure (SMAP) and central ve- been primed with their usual blood vol- nous pressure (CVP) are both 10 mmHg; CO is 1 L/min (B) when SMAP rises to 29 mmHg and ume, blood again moved around the circu- CVP falls to 9 mmHg; and CO is 5 L/min (C) lation at a rate of 5 L/min, which is the nor- when SMAP rises to 105 mmHg and CVP falls mal resting value for both cardiac output to 5 mmHg. and venous return.

6. The Effects of CVP on to be. We could make a graph that shows Venous Return the relationship between CVP and venous return (Fig. 8-11). For example, when the Let us focus for a moment on the venous heart is stopped, venous return falls to 0 L/ part of the model in Figure 8-10. For blood min, and CVP rises to 10 mmHg (Fig. 8- to flow from peripheral to central veins, 11,A, point A), which is the MCFP. As the pressure must be higher in the periphery heart starts beating (Figs. 8-9,B and 8- than it is centrally. Thus, the greater the 10,B), the right ventricle removes blood CVP, the smaller venous return would tend from the central veins so that the CVP falls

44 from 10 to 9 mmHg, and venous return in- creases to 1 L/min (Fig.8-11,A, point B). Once the heart is beating normally (Figs. 8- 9,C and 8-10,C), CVP decreases to 5 mmHg, and venous return increases to 5 L/min (8-11,A, point C).

In addition to the normal , other curves may be drawn to de- pict conditions in which the mean circula- tory filling pressure is increased or de- creased from normal (Fig. 8-11,A). For ex- Fig. 8-11. Venous Return Curves. Venous re- ample, when the plasma volume is in- turn has been plotted as a function of central creased (hypervolemia) or the walls of the venous pressure (CVP). (A) The normal ve- nous return curve includes points A, B, and C venous capacitance vessels are tensed (ve- from Figures 8-9 and 8-10. The normal curve noconstriction), the CVP will increase at is shifted to the right with an increase in the any given level of venous return. This will mean circulatory filling pressure (MCFP) and cause the venous return curve to shift to shifted to the left with a decrease in MCFP. (B) The normal venous return curve is rotated the right. Such rightward shifts in the ve- upward with arteriolar dilation and downward nous return curve are seen, for instance, in with arteriolar constriction without a change in patients with right ventricular failure MCFP. or in patients who have been overtrans- fused with isotonic saline. patients with severe diarrhea who are vol- On the other hand, when the blood volume ume depleted. is reduced (hypovolemia) or the capaci- Venous return curves may not only be tance vessels are relaxed (venodilation), shifted (in parallel), but also rotated up- the CVP will be decreased at any given ward or downward as the total peripheral level of venous return. This will cause the resistance is decreased or increased, re- venous return curve to shift to the left. spectively (Fig. 8-11,B). For example, an Such leftward parallel shifts in the venous increase in sympathetic outflow to arteri- return curve are seen, for instance, in pa- oles will increase total peripheral resis- tients who have been hemorrhaging or in tance (arteriolar constriction) and will

45 cause the venous return curve to be ro- tated downward. On the other hand, a de- crease in sympathetic outflow to arterioles will decrease the total peripheral resis- tance (arteriolar dilation) and will cause the venous return curve to rotate upward.

Note that sympathetic stimulation of arteri- oles produces opposite effects on venous return than does sympathetic stimulation of veins (see Fig. 8-11,A). Note also that the MCFP is not influenced by constriction or relaxation of arterioles. The reason for this is as follows. If the arterioles were more constricted when the heart was stopped in the experiment in Figure 8-9, systemic arterial blood pressure would have declined more slowly, but would even- tually have reached the same MCFP pres- sure of 10 mmHg. Similarly, if the arterioles had been more dilated when the heart was stopped, arterial pressure would have fallen more rapidly, but the same MCFP would be reached.

46 4

Graphic Analysis of Cardiac Output and Venous Return Graphic Analysis of Cardiac Output and Venous Return

Lecture 3-4: Graphic Analysis of Cardiac Output and Venous Return

48 situations. Because cardiac output must equal venous return (at least over a short time interval) a person's circulation will sta- bilize at the point of intersection between venous return and cardiac output. At rest, this point is at a CVP of about 5 mmHg (for the right ventricle) or at a PAWP of 10 mmHg (for the left ventricle) when venous return and cardiac output are 5 L/min.

Fig. 8-12. Cardiac Output and Venous Re- 1. Graphic Analysis of Exer- turn Curves. Cardiac output and venous re- cise turn curves from Figures 8-4 and 8-11A have been combined into a single graph. Point A on the graph in Figure 8-13 repre- Note that cardiac output must equal venous sents a person at rest with a cardiac out- return (when measured for more than a few beats), so that the circulation will stabilize at put of 5 liters/min and a CVP of 5 mmHg. points of intersection between the venous As he anticipates exertion, sympathetic return and cardiac output curves. That equi- cholinergic nerves cause vasodilation in librium point is normally at a cardiac output (or venous return) of 5 L/min and a CVP of 5 skeletal muscle and a decrease in the total mmHg (or PAWP of 10 mmHg). peripheral resistance. This causes an in- crease in venous return and results in an upward rotation of the venous return curve. Note that the curve is rotated up- We can now combine the curves for car- ward rather than shifted in parallel to the diac output and venous return as a func- left, so that the MCFP (i.e., the pressure tion of CVP (or PAWP) into a single graph when cardiac output and venous return are (Fig. 8-12). Similar graphs have been em- 0 liters/min) has not changed. As a conse- ployed by Guyton, who used right atrial quence of this decrease in total peripheral pressure as the independent variable, to resistance, and a relatively normal heart analyze the relationship between cardiac cannot handle the excessive load (high output and venous return in a variety of common physiological as well as clinical output failure). A good example of high

49

Fig. 8-13. Cardiac Function Curves during Exer- Fig. 8-14. High Cardiac Output Failure in Severe cise. Cardiac output and venous return have Anemia. been plotted as a function of CVP. Anticipation of Cardiac output and venous return have been plot- exercise decreases total peripheral resistance ted as a function of CVP (or PAWP) in a case of and thereby causes upward rotation of the ve- severe anemia. As the anemia increases in sever- nous return curve to a new equilibrium point B. ity, the total peripheral resistance progressively Further dilation of muscle arterioles during exer- decreases and the venous return curve rotates cise rotates the venous return curve further up- upward and to the right, resulting in an increase ward to point C. Sympathetic stimulation of the in cardiac output from A to B to C. The increase heart increases myocardial contractility and heart in cardiac output is associated with a significant rate, causing an upward (and leftward) shift of increase in CVP and in PAWP, causing symp- the cardiac output curve to the final equilibrium toms of peripheral edema and congestive heart point D. At point D, cardiac output and venous re- failure, respectively. turn are twice the resting values (A), with only a minimal increase in PAWP (or CVP).

less than 7 gm/dL, his total peripheral resis- tance gradually decreased, presumably cardiac output failure was a 95 year-old due to a combination of a diminished man with severe anemia. Let us assume blood viscosity and release of vasodilator that he was at point A in figure 8-14 when substances from hypoxic tissues. His car- he was not anemic. As his hemoglobin con- diac output increased progressively from A centration gradually fell from 15 gm/dL to to B to C as his venous return curve ro-

50 tated upward. Unlike a young person with a normal heart (Fig. 8-13), the 95 year old man, whose heart had been driven exces- sively for months, was incapable of shifting his cardiac output curve to a higher level. As a consequence, his PAWP and CVP were elevated and he had pulmonary and peripheral edema, respectively.

2. Graphic Analysis of Shock

When tissues are inadequately perfused with blood a person is said to be in shock. Shock can result from diminished venous Fig. 8-15. Circulatory and Cardiogenic Shock. return, i.e., circulatory shock, or from Cardiac output and venous return curves have pump failure, i.e., cardiogenic shock (Fig. been plotted as a function of CVP or PAWP for right or left ventricles, respectively. The fall in car- 8-15). Note that in circulatory shock CVP diac output in circulatory shock is caused by a and PAWP are decreased; whereas, in car- downward shift in the venous return curve, diogenic shock these pressures are in- whereas the fall in cardiac output in cardiogenic creased. shock is caused by a downward shift in the car- diac output curve. Note that CVP (or PAWP) is low in circulatory A. Circulatory Shock shock, but high in cardiogenic shock.

Circulatory shock may result from a de- crease in blood volume (hypovolemic shock), from loss of sympathetic vasomo- had ruptured her spleen (Fig. 8-16). Inter- tor tone (neurogenic shock), allergic reac- nal hemorrhage resulted in a decreased tions (anaphylactic shock), or from toxins mean circulatory filling pressure and a shift in the venous return curve to a lower level. released in certain infections (septic At this new equilibrium point (B), her car- shock). diac output had decreased to about one- Let us consider case where a young half of normal, resulting in a decrease in woman (Michelle in series 2, episode 1), blood pressure. Within seconds the barore-

51 ceptor reflex increased heart rate and car- diac contractility, moving the equilibrium point to a higher cardiac output curve, and sympathetic stimulation decreased the compliance of capacitance vessels, which shifted the venous return curve upward and to the right, resulting in a new equilib- rium point C. This latter effect, however, was offset by intense (by sympathetic nerves and high circulating concentrations of epinephrine acting on alpha-1- adrenergic receptors of vascular smooth muscle) that caused the venous re- turn curve now to rotate downward, result- ing in a decrease in cardiac output to point D. This was the price that had to be paid Fig. 8-16. Hemorrhagic Shock. Cardiac output and venous return curves are plotted for a pa- to maintain blood pressure as high as pos- tient, Michelle, with internal bleeding from a sible in order to perfuse the most vital or- ruptured spleen. Initial blood loss resulted in a gans - the brain and the heart. In other downward depression of the venous return curve and a shift in the equilibrium point from words, the reduction in cardiac output was A to B. Compensation occurred by sympa- more than offset by the increase in total pe- thetic stimulation of the heart, making it con- ripheral resistance, so that blood pressure tract more rapidly and more forcefully, and by venoconstriction. This shifted the equilibrium increased (BP = CO x TPR). point from B to C, where both the venous re- turn and cardiac output curves were raised. The intense vasoconstriction lowered capil- Cardiac output fell subsequently, however, lary blood pressure, which facilitated reab- from C to D, as sympathetic arteriolar constric- sorption of fluids from the interstitium. As tion rotated the venous return curve down- ward. Michelle was admitted to the hospital in this fluid was slowly added to plasma, the this state of shock and was treated with intrave- venous return curve shifted to the right. To nous 0.9% NaCl, which shifted the venous re- continue to increase plasma volume and turn curve upward and the equilibrium point from D to E. venous return, isotonic saline (and later whole blood) were infused intravenously in the hospital, which moved cardiac output

52 to point E. As the plasma volume returned to normal, the intense sympathetic outflow was no longer needed, and her pulse slowed and became fuller and her color re- turned as the compensatory vasoconstric- tion of skin vessels subsided.

B. Cardiogenic Shock

When Mr. M first came to the hospital for help, he was in a state of compensated heart failure. His ECG showed evidence of an inferior myocardial infarction, which he had suffered several years earlier. The Fig. 8-17. Compensated Heart Failure. Car- curves in Figure 8-17 reconstruct the se- diac output and venous return curves for Mr. M. Following a myocardial infarction, cardiac quence of events that took place immedi- output dropped to a lower function curve and ately following the heart attack. the equilibrium point moved from A to B. Com- pensation occurred by venoconstriction and As his left ventricle was injured as a result mobilization of fluids from the interstitium, shift- of the coronary occlusion, his cardiac out- ing the equilibrium to point C. Increased sym- pathetic stimulation of the heart, in turn, raised put curve decreased and he stabilized at a cardiac output to a higher function curve so new equilibrium point B, where cardiac out- that complete compensation (normal cardiac put was reduced and pulmonary artery output at rest) was obtained at point D. At point D the PAWP is elevated above normal, wedge pressure increased. The fall in and the cardiac reserve is diminished. blood pressure resulted, perhaps, in a short spell of dizziness or fainting, and cer- tainly in a feeling of weakness. Within sec- onds, however, the baroreceptor reflex initi- C). This action, aimed at increasing cardiac ated the compensatory responses, which output, is reserve, which he lost and which we have already considered in hemor- he needed when he had to exert himself. rhagic shock. Briefly, sympathetic outflow He was not normal in another important re- tenses capacitance vessels, which shifts spect. His pulmonary artery wedge pres- the venous return curve to the right (point sure was significantly higher than normal. The difference between this pressure and

53 a pulmonary artery wedge pressure of about 27 mmHg is a safety margin for avoiding pulmonary edema.

Mr. M was in a precarious situation without an adequate cardiac reserve when his atria started to fibrillate and his ventricles con- tracted irregularly at about 130 beats/min. Because of the reduced stroke volume per beat, his cardiac output curve fell and he arrived at point C in Figure 8-18. Note that this curve spells trouble. It is so flat that even at its highest point it does not reach Fig. 8-18. Decompensated Heart Failure. a minimum cardiac output for sustaining Cardiac output and venous return curves are tissue metabolism at rest (about 5 L/min). shown for Mr. M after he had compensated Although the heart is once again bom- for a myocardial infarct (Fig. 8-17,D). He then develops atrial fibrillation and moves to barded with sympathetic stimuli, it has a lower cardiac function curve and a new been stimulated for too long and norepi- equilibrium point C. His heart is incapable of nephrine receptors have been down- compensating by moving to a higher cardiac function curve with sympathetic stimulation, regulated. The kidney, however, attempts but his kidneys function normally and retain to compensate for the reduced cardiac out- more salt and water, causing the venous re- put by retaining more salt and water (this is turn curve to shift progressively to the right mediated, as usual, by sympathetic stim- from C to F to G. Note that the cardiac output curve is flat, so uli, vasopressin, and aldosterone). Al- that these shifts in the venous return curve though renal compensation usually works do not increase cardiac output to the mini- well with a normal or near-normal heart, mum requirement of 5 L/min (at rest). Moreo- ver, as PAWP exceeds a value of about 27 this strategy becomes counterproductive mmHg, pulmonary edema develops. in a heart with a flat cardiac output curve. As days pass, the retained salt and water shifts the venous return curve progres- sively to the right from point C to E to F to monary artery wedge pressure is continu- G. Not only is the increased venous return ously rising and the lungs are being pro- not increasing cardiac output, but the pul- gressively flooded with more and more

54 edema fluid. In addition, the ventricular angiotensin-converting enzyme inhibi- chambers are becoming progressively tors (e.g.,ramipril), aldosterone antago- more dilated, causing wall tension to rise nists (e.g.,spironolactone), and beta- according to the Laplace equation (T = P x adrenergic blockers (e.g.,metoprolol, carv- R/2). This means that the heart must now edilol). generate a greater than normal contractile force to overcome wall tension to eject a normal stroke volume.

Decompensated heart failure, as Mr. M had on his second visit to the hospital is a medical emergency requiring immediate in- tervention. Treatment included measures aimed at moving the venous return curve back to the left. This was accomplished by decreasing the on the heart by ad- ministering intravenous furosemide. In addi- tion, carvedilol was administered to im- prove cardiac function and reduce the af- terload which moved the cardiac output curve to a higher level.

Activation of the sympathetic nervous sys- tem and the renin-angiotensin-aldosterone system are essential in increasing cardiac output acutely following myocardial injury. However, the long term effects of these two systems results in remodeling, hyper- trophy, and apoptosis of the myocardium which results in a decrease in cardiac out- put. Indeed, clinical trials have shown that mortality from congestive heart failure is significantly reduced with the use of

55 5

Review Interactive Questions

57 This is Mr. Bach.

Chief Complaint: He His pupils are small fainted on standing and constrict even up and is bleeding more as you move from a cut on his fore- your finger towards head. his eyes, but not when you shine a light into them.

You hear an early dia- His neck veins are stolic decrescendo distended 15 cm murmur. above his sternal an- gle.

You hear wet rales on His BP is 160/60 auscultation. mmHg and he has a Corrigan Pulse.

He cannot stand with Swelling, discolora- his feet together and tion, no hair, foot ul- eyes closed. Can’t cer. feel if you move his big toe up or down. Can’t feel vibrations of your tuning fork.

1 2 3 4 5 6 7 8

58 Case: Essay/Small Group Questions

59 1. How does the Baroreceptor Reflex 11. Why does left heart failure eventually keep you from fainting when you stand lead to right heart failure? up? 12. What are the signs and symptoms of 2. Define Orthostatic Hypotension. What right heart failure? may cause it? 13. Draw cardiac output and venous return 3. Why did Mr. Bach have a Corrigan curves for Mr. Bach and explain how he Pulse? compensated for his aortic insufficiency.

4. Draw the changes in intraventricular, 14. Why do patients with congestive heart atrial and aortic pressures during a car- failure complain of nocturia? diac cycle for a healthy person and for Mr. Bach who has aortic insufficiency. 15. Why is the renal filtration fraction in- creased when cardiac output declines? 5. To the graph above (4) add the mur- murs of aortic insufficiency and the Aus- 16. How do kidneys retain more salt and tin Flint murmur and explain their ori- water in congestive heart failure? gins. 17. What causes pre-renal azotemia? 6. Why are diastolic murmurs not as loud 18. How do you test for the Argyll Robert- as systolic murmurs? son pupil? 7. Why does aortic insufficiency cause left 19. What is tabes dorsalis? heart failure? 20. How can you diagnose a defect in pro- 8. What ECG changes would you expect prioception? to see in ventricular hypertrophy?

9. Why did Mr. Bach have congestive heart failure and what are the signs and symp- toms of this condition?

10.What causes dyspnea and why did Mr. Bach have dyspnea on exertion?

60 Lecture: Essay/Small Group Questions

61 Cardiac Function Curves Cardiac Output/Venous Return Plots

1. What is the relationship between cardiac 9. Draw cardiac output/venous return plots output and ventricular filling pressure? for a person who is exercising, hemor- rhaging, or suffering an acute myocar- 2. Name conditions that increase or de- dial infarct. crease the cardiac output. 10. 3. Name high cardiac output states that are caused by a decreased in total periph- eral vascular resistance.

Venous Return

4. How does gravity affect venous return?

5. How does inspiration facilitate venous return?

6. Why does the use of PEEP (positive- end-expiratory pressure) on a ventilator de- crease cardiac output?

7. What is the mean systemic filling pres- sure?

Venous Return Curves

8. How is the venous return curve shifted with plasma volume changes or with changes in venous and arteriolar muscle tone.

62 True/False Quiz

63 Directions: An answer is “True” (A) when the complete statement(s) is (are) correct. Otherwise the answer is “False” (B).

Question 1 of 10 Cardiac Output is determined by Venous Return.

A.

B.

Check Answer

64 6 More Episodes in iBooks

Physiology as a Country Doc

Series 1. Cardiac Physiology as a Country Doc by Patrick Eggena, M.D.

Episode 1. Electrophysiology Episode 2. The EKG Episode 3. Heart Attack Episode 4. Irregular Beats Episode 5. Excitation-Contraction Episode 6. The Heart as a Pump Episode 7. Murmurs and Gallops

Series 2. Circulatory Physiology as a Country Doc Episode 1. Episode 2. Regulation of the Circulation Episode 3. Cardiac Output and Venous Return