Circulatory

Physiology
As a Country Doc
Episode 3
Cardiac Output
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: patrickeggena@yahoo.com

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 Heart-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 blood pressure.”

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 pulse increase by 10%?”

Doc: “Yes - Mr. Bach’s pulse increased in
response to the pressure drop --after his
baroreceptor reflex kicked in.”
Kay: “The sensors for this are in the ca-
rotid sinus?”
Kay --your nurse is taking night courses to be-
come a nurse practitioner. She comes along
when you are making house calls.
Doc: “That’s his problem. That’s why he
fainted. That’s his chief complaint. It’s why
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
to the vasomotor center in the medulla
and back out to the veins were probably
not conducting impulses fast enough?”
Doc: “Could be. Patients with peripheral
neuropathy, for example, tend to faint on
standing up suddenly. They have problems
with nerve conduction.
Kay: “Like in patients with diabetes?”
Doc: “Yes --diabetic neuropathy is a quite
common cause of orthostatic hypoten-
sion.”
Kay: “How about medicines?”
Doc: “Yes --patients receiving medicines
for hypertension --quite common --espe-
cially alpha-1-adrenergic blockers.”
Kay: “I did an internship on a psychiatric
ward. Many of the antipsychotic medi-
cines do this also.”
Doc: “Not uncommon side effect of medi-
cines. But we did ask his daughter if he
had diabetes or was taking any medicines
for hypertension or for his PTSD from the
Korean War, and she said “No”.”
Kay: “But what if he was dehydrated or
bleeding internally or had diarrhea or
something that depleted his blood vol-
ume? That can also cause orthostatic
hypotension, can’t it -- Doc?”
Doc: “Yes for sure. Very common. If his
veins are nearly empty, tensing up on them
won’t increase pressure by much. But is
plasma volume depletion a likely explana-
tion here --considering his blood pres-
sure?”
Kay: “No --he was not in shock --not
with a systolic pressure of 160 mmHg
and with the strong pulse that he had.”
Doc: “His strong pulse is called a Corrigan
pulse or a water-hammer pulse. It was
due to his high pulse pressure.”
Kay: “You mean the large difference be-
tween his systolic and diastolic blood
pressure?”
Doc: “Yes, it was quite large because of
his great stroke volume.”
Kay: “It’s as if he were exercising and all
that blood was going to his muscles.
But it wasn’t. So why did he have such
large stroke volumes?”
Doc: “Well --you listened to his heart.
What did you hear?”
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 ventricle, there-
Doc: “He has aortic insufficiency. His aor-
fore, fills during diastole 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
the damaged aortic valve. So when the
left atrium contracts toward the end of di-
astole blood ejected through the mitral
valve becomes turbulent and creates the
pre-systolic murmur, the so-called Austin
Flint murmur.”
Kay: “His left ventricle is working hard
--has been for a long time --and now it
is hypertrophied. Right?”
Doc: “How do you know that it is hypertro-
phied?”
Kay: “Because the S-wave in lead V1
plus the R-wave in V5 is greater than 35
mm. --- You taught me that the other
day. But I don’t understand why the ST
segment is depressed in lead V5.”
Doc: “Left ventricular strain --sloping of
the ST segment --indicates endocardial
ischemia.”
Kay: “Is his left ventricle failing?”
Doc: “Well, what do you think? What did
you hear when you listened to his lungs?”
Kay: “His lungs didn’t sound normal.
Where those wet rales I heard?”
Doc: “Yes --wet crackles from pulmonary
edema. Why were his lungs wet?”
Kay: “Blood was backing up into his
lungs because his left ventricle couldn’t
handle the load?”
Doc: “Blood wasn’t really backing up, but
a higher pressure was required to fill his
left ventricle because it was hypertrophied
and stiff.”
Kay: “So more blood was filtered across
the capillaries in the lungs because cap-
illary pressure was increased?”
Doc: “Yes --and the lymphatics couldn’t
quite handle the increased load. Couldn’t
return all the extra fluid around his alveoli
back to the circulation.”
Kay: “I asked him if he got short of
breath when he lies down, and he said
“Yes”. And he said that he slept with
his head on three pillows.”
Doc: “Why did he use several pillows?”
Kay: “I know, this is called orthopnea
and it is due to the edema fluid in his
legs moving back into his lungs at
night.”
16
Doc: “And also, when he lies flat more of
his lungs are below the level of the tricus-
pid valve. So hydrostatic pressure is
higher in more lung capillaries than usual
and more fluid is filtered into the interstitial
spaces around the alveoli.”
Kay: “So more of his lung is under wa-
ter?”
Doc: “Yes, so-to-speak.”
Kay: “He also said that he has asthma
attacks at night which adds to his prob-
lem with breathing. But I didn’t hear any
wheezing when I listened to his lungs.”
Doc: “He has cardiac asthma which is dif-
ferent from regular asthma.”
Kay: “How so?”
Doc: “In cardiac asthma it is edema fluid
that wells up from the alveoli into the bron-
chioles distending their walls and imped-
ing air flow. This shortness of breath that
comes on at night is called paroxysmal
nocturnal dyspnea or PND for short.”
Kay: “He said that these attacks were so
bad sometimes that he had to sit up
with his legs dangling over the side of
the bed.”
Doc: “Yes --to move fluid from his lungs
back into his feet.”
Kay: “And he also said that he can’t
make it all the way up the stairs to his
bedroom without having to stop several
times because he runs out of breath.”
Doc: “Yes, he has dyspnea on exertion or
DOE for short.”
Kay: “Doc, I noticed that the residents in
the hospital tend to speak in abbrevia-
tions and broken sentences to one-
another, why is this?”
Doc: “They are usually in a rush and sort of
know how to complete a sentence started
by one of their colleagues without it being
vocalized. A lot of medicine is repetition.”
Kay: “Alright, so what’s with Mr. Bach’s
DOE?”
Doc: “When he gets ready to climb the
stairs, his pre-motor cortex sends im-
pulses over several pathways all the way
down to the muscles in his legs that are go-
ing to do the work. Arterioles dilate and as
muscle start to contract pre-capillary
sphincters click open in response to meta-
bolic by-products such as carbon dioxide
and adenosine that are released from cells.
And his leg muscles get warm from the
17
heat generated from the brake down of
ATP molecules and this along with release
of endothelial relaxing factors dilates ves-
sels even more. These mechanisms fur-
nish Mr. Bach’s leg muscles with the oxy-
gen and nutrients needed to climb the
steps.”
Kay: “Okay, Doc --got it. What next?”
Doc: “Now all this extra blood that rushes
to his leg muscles in arteries comes back
out in his veins and is returned to the right
ventricle which pumps more into his
lungs.”
Kay: “Well, that happens to all of us
when we exercise. So what is different
with Mr. Bach?”
Doc: “You have a normal cardiac reserve,
where your left ventricle pumps about 5
liters/minute at rest, but on exercising can
pump perhaps 15 liters/minute or more.
But Mr. Bach does not have much of a car-
diac reserve. His heart can pump just
about enough blood to get by at rest.”
Kay: “And so the blood that is not
pumped by the left ventricle is left in
the lungs and takes his breath away?”
Doc: “Yes --he becomes dyspneic. Hence
the term dyspnea on exertion.”
Kay: “He feels short of breath --is dysp-
neic -- because he is not getting
enough oxygen. Right?”
Doc: “You might think so because he is, in-
deed, not getting enough oxygen. But air-
hunger --or not being able to catch ones
breath -- is due to the excessive work that
his inspiratory muscles have to do to dis-
tend his alveoli which have become stiffer
because of the surrounding edema fluid. It
is this extra work that gives him the sensa-
tion of dyspnea. It’s a subjective feeling
--a little bit like pain.”
Kay: “That’s interesting. Now I also no-
ticed that his neck veins were dis-
tended. I guess this means that his
right ventricle was also failing. But
why? It wasn’t working overtime like
his left ventricle?”
Doc: “Kay, but it was. It was also working
much harder because left ventricular fail-
ure invariably leads eventually to right
heart failure.”
Kay: “Why is that?”
Doc: “When the left ventricle fails and fluid
accumulates in the lungs, the amount of
oxygen in blood decreases and this
causes arterioles in the lung to constrict.”
18
Kay: “But I thought blood vessels re-
laxed when oxygen is lacking. Isn’t this
how more blood flows to tissues that
need it? Remember, “autoregulation”
we talked about yesterday?”
Doc: “Big difference between autoregula-
tion in peripheral tissues and in the lung.
In the lung a decrease in oxygen tension
causes constriction of blood vessels, not
relaxation.”
Kay: “But why?”
Doc: “ If a section of the lung is not getting
oxygen because a bronchus is plugged
with mucus, you don’t want to have blood
flowing to that section of lung. It won’t
pick up any oxygen or get rid of any car-
bon dioxide. In fact, blood flowing through
an unventilated section of lung is like a
right-to-left shunt -- allowing unoxygen-
ated venous blood to flow straight into the
arterial circulation as if you had poked a
hole in the interventricular septum. So no,
the response to hypoxia is reversed in the
lung.”
Kay: “But how do blood vessels in the
lung sense that oxygen is low and that
they ought to constrict?”
Doc: “There are receptor proteins in the
membranes of pulmonary vascular smooth
muscle that behave in some respects simi-
lar to hemoglobin in that they change their
conformation depending on the amount of
oxygen bound to them.”
Kay: “And this conformational change
with little oxygen around causes the
contraction?”
Doc: “Eventually, yes --but first the confor-
mational change in the protein closes a po-
tassium channel so that potassium diffu-
sion out off the smooth muscle cell is
slowed.”
Kay: “And that moves the membrane po-
tential away from the potassium equilib-
rium potential of -90 mV. Right? We
learned about the Nernst Equation and
membrane potentials not long ago in
class.”
Doc: “Good, Kay --the membrane poten-
tial becomes less negative at which point a
voltage-gated calcium channel in the mem-
brane opens and calcium ions flood the
cell and make it contract.”
Kay: “And this increases the resistance
against which the right ventricle has to
eject its stroke volume?”
19
Doc: “ Yes -- pulmonary resistance, that is
the afterload on the right ventricle, in-
creases and it eventually fails.”
Kay: “What do you mean by “fails”?”
Doc: “Fails to ejected 2/3rds of its end-
diastolic volume.”
Kay: “So his right ventricle is not con-
tracting fast enough?”
Doc: “Yes, not fast enough in the time it
has to contract during systole.”
Kay: “So what happens?”
Doc: “It increases its end-diastolic vol-
ume.”
Kay: “A bigger heart?”
Doc: “Yes --the ventricular chamber dis-
tends and with the help of the Frank-
Starling mechanism manages to eject a
bigger stroke volume.”
Kay: “But that requires more energy and
more work. Doesn’t it?”
Doc: “Yes, it’s inefficient because of the
LaPlace equation.”
Kay: “I remember: Wall tension equals
pressure times radius.
Doc: “Not quite. In a sphere, like an alveo-
lus or ventricle, it’s twice the radius. But
you’re right, wall tension will be increased
so that more ATP molecules and more oxy-
gen and more coronary blood flow will be
needed to force the blood out. Nothing is
for free.”
Kay: “But doesn’t the ventricle eventu-
ally hypertrophy?”
Doc: ”Yes, it does, and with hypertrophy
wall tension is distributed over more sar-
comeres. This decreases overall wall ten-
sion. But now the ventricle becomes
stiffer -- more difficult to fill.”
Kay: “So his CVP has to go up?”
Doc: “Yes --his neck veins should have
been filled to no more than about 8 cm
above his sternum.”
Kay: “That’s because the tricuspid valve
is zero and it is about 5 cm below the
sternum?”
Doc: “Right. Total pressure about 13 cm
H2O or roughly 10 mmHg.”
Kay: “Specific gravity of mercury is
about 13?”
Doc: “Yes, Kay, if I remember correctly.”
20
Kay: “So blood then started flowing
backwards into his legs causing his
edema?”
Doc: “No --blood keeps flowing toward the
heart even when the CVP is high. The only
difference is that a higher pressure is now
required in foot capillaries to keep blood
moving upwards to the heart.”
Kay: “Doc, that’s what I’m saying. Blood
flows backwards into the feet to raise
pressure to keep blood moving.”
Doc: “No --nothing flows backwards.
There are one-way valves in the large veins
that keep that from happening. No --
blood stays in the feet. Won’t move until
enough has accumulated to generate the
recoil pressure required to move blood
against gravity up to the heart.”
Kay: “And the increase in capillary pres-
sure then causes more fluid to be fil-
tered into the interstitial spaces of Mr.
Bach’s feet --creating edema?”
Doc: “Yes --that is, if the lymphatics are
overwhelmed and can’t keep up with the
influx.”
Kay: “What keeps his feet and legs from
getting bigger and bigger from all that
fluid?”
Doc: “As edema fluid distends the intersti-
tial spaces, elastic tissues in these spaces
are stretched and create a back-pressure
which eventually stops more fluid from en-
tering this compartment.”
Kay: “But won’t his plasma volume be
depleted by the amount of extra fluid
ending up in his feet and legs?”
Doc: “His plasma volume is kept at a near
normal level by his kidneys.”
Kay: “How do his kidneys do that?”
Doc: “As fluid is lost to interstitial spaces,
less blood is returned to the right atrium
where low pressure baroreceptors in the
subendocardium sense the decrease in
blood volume.”
Kay: “Plasma volume receptors?”
Doc: “Yes --but the body can’t measure
blood volume, it only has sensors for pres-
sure. But these low pressure receptors in
effect measure volume. You are right.”
Kay: “So these volume receptors send
impulses to the vasomotor center which
increases sympathetic outflow to the
kidney?”
21
Doc: “Yes --and sympathetic nerves con-
strict both the afferent and efferent arteri-
oles of glomeruli in his kidneys.”
Kay: “Why not just clamp down on the
afferent arteriole to decrease filtration
at the glomeruli and minimize loss of flu-
ids in the urine?”
Doc: “By clamping down on the efferent
arteriole as well, you increase the filtration
fraction, which enhances salt and water re-
absorption in the proximal tubule.”
Kay: “We had this in class: The filtration
fraction is equal to the glomerular filtra-
tion rate divided by renal plasma flow.
Right?”
Doc: “Yes, Kay --so if you clamp down on
both the afferent and the efferent arteriole
--that is increase two resistances in series
--the filtration fraction increases more than
if you had only constricted the afferent arte-
riole.”
Kay: “Got it Doc. But why? Why filter
relatively more plasma fluid only to reab-
sorb it again in the proximal tubule.
Seems like a waste of energy.”
Doc: “But that’s how the kidney can still
get rid of waste products that are filtered
and --unlike salts-- do not have special
transporters to move them back into blood
in the proximal tubule.”
Kay: “You mean like the transporters for
glucose and amino acids that are fil-
tered and reabsorbed in the proximal tu-
bule?”
Doc: “Yes --potentially toxic substances
that have been digested and absorbed into
blood in the gut are filtered in the glomeruli
and because these foreign substances
don’t have transporters in the proximal tu-
bule are left behind in tubular fluid and are
excreted in a smaller than usual volume of
urine.”
Kay: “So you are saying that when the
kidney is not getting its usual share of
blood it still tries its best to get rid of
wastes.”
Doc: “Yes, Kay --that’s the idea. That is
why the kidney has these two resistances
in series in the glomeruli. A clever way of
making it do its job more efficiently with a
lower rate of glomerular filtration. It’s not
just sympathetic stimulation that increases
the filtration fraction, but also hormones
such as angiotensin II and epinephrine.”
Kay: “If the glomerular filtration rate is
decreased, the concentration of urea
22
and creatinine in blood will increase.
Won’t it, Doc?”
Doc: “Yes, if there is a significant decrease
in renal perfusion or if there has been dam-
age to the glomeruli. That is how we can
tell that kidney function is reduced. But if
function is reduced because of decreased
perfusion, the concentration of urea will
rise more than the concentration of creati-
nine. That is, the ratio of BUN/creatinine
will increase.
Kay: “Is that important?”
Doc: “That is how we can distinguish a re-
versible from an irreversible decrease in
glomerular filtration due to destruction and
loss of glomeruli.”
Kay: “I don’t understand why the con-
centration of urea rises more than the
concentration of creatinine with de-
creased renal blood flow.”
Doc: “Creatinine is filtered by the glomeruli
and never reabsorbed by the nephron. By
contrast, urea is filtered but also reab-
sorbed from tubular fluid --more so when
the kidney is underperfused. Therefore, a
rise in the BUN/creatinine ratio in blood is
called pre-renal azotemia to distinguish
this reversible cause of diminished kidney
function from irreversible loss of glomeruli
where both BUN and creatinine rise propor-
tionally in blood.”
Kay: “So do you think Mr. Bach has pre-
renal azotemia because his heart is fail-
ing?”
Doc: “No, not at this time. Although we
don’t know for sure without analyzing a
blood sample for urea and creatinine. He
has presumably compensated for the de-
creased blood flow to his kidneys by retain-
ing more salt and water and raising his car-
diac output back to normal -- at least while
he is resting. So his renal blood flow is
now normal.”
Kay: “So it is only intermittently that his
kidney go into this salt and water retain-
ing state?”
Doc: “Yes, especially during the day when
gravity causes blood to pool in his legs.
That’s when he retains more salt and wa-
ter.
Kay: “From the proximal tubule because
of the increased filtration fraction?”
Doc: “Yes, and from the collecting ducts
because of vasopressin and aldosterone.”
Kay: “Is this because more vasopressin
and aldosterone are released into the
23
circulation when low pressure barore-
ceptors in the atria are stretched less
than usual?”
Doc: “Yes --and even much more so
should high pressure baroreceptors in the
carotid sinuses sense a drop in blood pres-
sure as they did, for example, when Mr.
Bach stood up and fainted.”
Kay: “So Mr. Bach collects extra salt and
water as he walks around during the
day and deposits it in his feet and legs
as edema, and then at night gets rid of
it again?”
Doc: ”Yes --at night when this fluid leaves
the legs and enters the circulation, the vol-
ume receptors in the atria are stretched
and they turn off vasopressin and aldoster-
one secretion.”
Kay: “Is that why Mr. Bach said that he
couldn’t sleep because he had to go to
the bathroom several times at night?”
Doc: “Yes he had nocturia --not only from
lack of vasopressin and aldosterone but
also because another hormone, the so-
called atrial natriuretic peptide. This hor-
mone is released from atrial muscle cells
when they are stretched and it increases
salt excretion by the kidney.”
Kay: “Yes, Doc. We learned that noc-
turia is a common symptom in patients
with congestive heart failure.”
Doc: “It probably helps Mr. Bach breathe a
little easier than if this fluid ends up in his
lungs at night.”
Kay: “Doc, his legs and feet looked aw-
ful. The swelling, the discoloration, no
hair, and the ulcer.”
Doc: “True, this is from stasis dermatitis.
Edema increases the diffusion path for oxy-
gen and nutrients -- a greater distance be-
tween capillaries and skin. Hair no longer
grows. Red cells burst leaving behind iron
deposits which stain his skin.”
Kay: “And that ulcer on his ankle is not
going to heal unless he takes care of
himself.”
Doc: “You are right. He has to keep the
leg up high as much as possible to reduce
the swelling.”
Kay: “But he has no feeling in his feet.
And he was also pretty unsteady. No
warning, no pain when he bumps into
things and gets an abrasion or a cut
which will then go unnoticed and fester.
Why is this, Doc? Why can’t he feel his
feet?”
24
Doc: “He probably has peripheral neuritis
and perhaps something more serious that
is interfering not only with pain sensation
but also with balance and his position
sense.”
Kay: “Could peripheral neuritis be re-
sponsible for his orthostatic hypoten-
sion?”
Doc: “Possibly.”
Kay: “Embarrassing -- when you asked
this nice old man if he had syphilis.”
Doc: “Yes, Kay --taking a sexual history is
awkward -- but important.”
Kay: “And when he started reminiscing
about the girls in Munich a long time
ago.”
Doc: “Kay, it’s sometimes difficult not to ap-
pear impatient when taking a history. But
you have to be polite while keeping your
patient focussed on what is essential to
making a diagnosis.”
Kay: “Well, he admitted to having had
gonorrhea, but he said nothing about
syphilis.”
Doc: “His treatment for gonorrhea masked
the more serious venereal disease which
he had also acquired. That is why he
should have been tested with the VDRL
test for syphilis, which was not done at the
time. And so his condition quietly pro-
gressed to the final stage of tertiary syphi-
lis, which is causing him problems now --
decades later.”
Kay: “How do we know that he has terti-
ary syphilis without the VDRL test?”
Doc: “He has the Argyll-Robertson pupil
which is almost diagnostic for syphilis.”
Kay: “You tested for that when you al-
most poked him in the eye?”
Doc: “Yes, his pupils were small, and they
constricted to an even smaller size when I
moved my finger towards his nose. That’s
expected --a normal accommodation re-
sponse. But they did not constrict when I
was shining a light into his eyes. That’s ab-
normal. That’s the Argyll-Robertson pu-
pil.”
Kay: “Why did he have aortic insuffi-
ciency?”
Doc: “Syphilis is caused by treponema
pallidum -- a spirochete, a little worm-like
organism -- that gets into the vasa va-
sorum of the ascending aorta.”
25
Kay: “You mean the little blood vessels
that supply the tissues in the wall of the
aorta?”
Doc: “Yes --and these little vessels get
clogged up by the spirochete, so the wall
of the aorta doesn’t get the nutrients it
needs and is weakened. “
Kay: “Yes, but what does that have to do
with a leaky aortic valve?”
Doc: “I’m coming to that. The weakened
wall of the ascending aorta bulges a little.
This increases it’s radius. As the radius in-
creases, so does wall tension.”
Kay: “Oh, I know -- the Laplace equa-
tion again, but now in a blood vessel
where wall tension equals pressure
times the radius. So an increase in the
radius of the aorta will increase its wall
tension?”
Doc: “And as wall tension increases, a few
more fibers in the wall rupture and the
aorta bulges a little more. And this, in turn,
increases tension which ruptures more fi-
bers and so forth.”
Kay: “Like a weak spot in a tire --usually
ends in a blow-out?”
Doc: “Right --that’s what one fears may
happen with aneurisms. But before this
happens the aneurism stretches the aortic
valve so that the leaflets no longer close
tightly during diastole. Hence the back-
leak of blood which you heard as an early
diastolic decrescendo murmur.”
Kay: “So what are they going to do for
him?”
Doc: “He needs a thorough workup by a
cardiologist and a neurologist, including
the VDRL test, which he didn’t get several
decades ago in the Army -- and a spinal
tap to examine his cerebrospinal fluid.”
Kay: “And he needs a new aortic valve
and penicillin shots.”
Doc: “A new valve, yes, but no penicillin
--remember he is allergic to it. So they will
give him something else, like doxycycline
perhaps.”
Kay: “The neurologist can also see
what’s happening with his balance. He
didn’t know if his big toe was up or
down when you moved it and he had his
his eyes closed.
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 heart rate.

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-
portional to CVP (right ventricle) or PAWP
(left ventricle), cardiac output also in-
creases as a function of CVP or PAWP
(Fig. 8-4, normal function curve at rest). Be-
cause cardiac output also changes as a
function of heart rate and myocardial con-
tractility at any end-diastolic filling volume,
the normal (resting) cardiac function curve
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
depressed and/or heart rate is abnor-
mally slow. Conditions that raise the nor-
mal (resting) cardiac function curve in-
clude: sympathetic stimulation, beta-1-
adrenergic agonists, or cardiac glycosides.
Conditions that decrease the normal (rest-
Fig. 8-4. Cardiac Function Curves. Cardiac
output of the right or left ventricles has been
plotted as a function of the central venous
pressure (CVP) or pulmonary artery wedge
pressure (PAWP), respectively. The cardiac
output curve is shifted upward in conditions
that increase myocardial contractility and
(or) heart rate, provided that the increase in
heart rate is not excessive or prolonged. The
cardiac output curve is shifted downward in
conditions that decrease myocardial contrac-
tility and (or) heart rate.
ing) cardiac function curve include: para-
sympathetic stimulation (causing sino-
atrial and atrio-nodal conduction blocks),
beta-1-adrenergic antagonists, calcium
channel blockers, myocardial infarction,
valvular heart disease, atrial fibrillation, or
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
central veins and generates the filling pres-
sure of the right ventricle (and subse-
quently [via the PAWP] of the left ventricle)
will depend upon the amount of blood that
flows from the capillary beds of the various
organs and tissues of the body. Blood flow
through these capillary beds depends, in
turn, upon the various autoregulatory
mechanisms that allow blood to enter or-
gans and tissues. Thus, when tissues need
more blood to meet their metabolic needs,
vasodilator substances accumulate and
cause pre-capillary sphincters and metarte-
rioles to relax. As more blood flows to tis-
sues and organs, more is returned to the
heart and cardiac output increases, accord-
ingly. Therefore, cardiac output is regu-
lated by the sum of the individual meta-
bolic needs of the tissues. When more
blood is needed, for instance, with exer-
cise, skeletal muscle will take a larger frac-
tion of the cardiac output, which it will rap-
idly return via low resistance channels to
the veins. The CVP will increase and fill the
right ventricle more, so the right ventricle
will pump more blood into the pulmonary
artery. The PAWP, in turn, will increase and
fill the left ventricle more, so that the left
ventricle will pump more blood into the
aorta, from where the increased cardiac
output is delivered to exercising muscles.
Thus, in the normal heart, venous return de-
termines cardiac output.
1. Increased Venous Return
(and Cardiac Output) with
Shunts and Altered Meta-
bolic States
Venous return and cardiac output are nor-
mally regulated by the metabolic needs
and functions of the various organs and tis-
sues that make up the body. There are
times, however, when blood flow through
tissues is excessive, for example when tis-
sue metabolism is abnormally increased
(e.g., hyperthyroidism) or when blood is by-
passing capillary beds altogether by flow-
ing via low resistance shunts between ar-
teries and veins (e.g., Paget's disease). In
both instances, the total peripheral resis-
tance is decreased without changing the
compliance of the capacitance vessels re-
sponsible for conducting blood back to the
heart. This increase in venous return re-
sults in increased cardiac output.
Let us illustrate this with a simulation (Fig.
8-5) of experiments carried out by Guyton
and colleagues on anesthetized dogs.
Catheters are inserted into a femoral artery
and vein, and the ends are connected by a
three-way stopcock. When the stopcock is
closed, only 5 L/min of blood flows
34

Fig.8-5. Effect of an Arterio-Venous Shunt on
Venous Return and Cardiac Output. A shunt
was created between the femoral artery and
vein in an anesthetized dog, and blood flow
through the shunt was regulated by a stop-
cock. When the stopcock was closed, venous
return and cardiac output was 5 L/min. When
the stopcock was opened, 5 L/min of blood
flowed through the shunt to the femoral vein,
which was added to the 5 L/min of blood al-
ready returning to the heart from various or-
gans and tissues. Venous return and cardiac
output were thereby increased to 10 L/min.
through capillary beds of various organs
and tissues and is returned to the heart.
When the stopcock is first opened, 5 L/min
of blood flows through the shunt and none
through the tissues. The sudden drop in to-
tal peripheral resistance causes a fall in
blood pressure, which activates the barore-
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-
Starling mechanism. This experiment illus-
trates that cardiac output is regulated by
venous return.
There are a number of conditions that are
characterized by an increase in cardiac out-
put where the high cardiac output state
can be ascribed to a primary decrease in
the total peripheral resistance (without a
change in venous compliance). This is
seen, for example, in patients with Paget's
disease, where extensive arterio-venous
fistulae are formed in bone. Also, during
the third trimester of pregnancy venous re-
turn and cardiac output increase markedly
as blood is shunted through low resis-
tance pathways in the placenta. For this
reason, young women with rheumatic val-
vular heart disease may not be aware of
their cardiac disability until they develop
35
signs and symptoms of congestive heart
failure in the late stages of pregnancy. Hy-
perthyroidism also is often associated
with an increased cardiac output, partly be-
cause the heart is stimulated to contract
more and tissues and is returned to the
heart. When the forcefully, partly because
an increase in tissue metabolism leads to
enhanced blood flow through capillary
beds. Marked peripheral vasodilation is
seen in beriberi (thiamine deficiency),
when glucose metabolism cannot proceed
normally. This condition causes high car-
diac output states and high output cardiac
failure when the heart cannot keep up with
the high venous return. (The heart also con-
tracts less forcefully than normal in beri-
beri.) We have already seen that severe
anemia in the man in case 6 can lead to
an increase in cardiac output. In this situa-
tion cardiac output increases as tissues de-
prived of oxygen vasodilate and return
more blood to the heart.
It must be emphasized that a decrease in
total peripheral resistance (e.g., by relaxa-
tion of arteriolar smooth muscle) will only
lead to an increase in venous return and in
cardiac output, provided that venous com-
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
a decrease in sympathetic outflow to the
vascular system - cardiac output de-
creases because blood pools in the veins
and is not returned to the heart.
2. Effect of Gravity on Ve-
nous Return (and Cardiac
Output)
Gravity is an important factor in venous re-
turn (Fig. 8-6). Blood in veins below the
level of the heart is subjected to gravity,
which pulls on the column of blood, dis-
tending vessels below the heart. Just look
at the veins in your hand, when your arm is
relaxed and hanging down by your side.
Now raise your arm and watch the veins in
your hand collapse as it passes the level of
your heart. The veins above the heart,
such as those in the neck, are normally col-
lapsed when a person is sitting or stand-
ing. As blood flows with gravity from the
head to the chest, it creates a partial vac-
uum in the venous sinuses of the cranium
that tends to siphon blood from arteries
into brain capillaries. The neurosurgeon
must be aware of this when operating on a
patient in the sitting position. If a vein in
the head or neck is cut, air may be sucked
into the heart, resulting in an air embolus.
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-
creasing their compliance.
(2) The major veins have one-way valves
pointing toward the heart. These valves,
when competent, break up the long col-
umn of blood between heart and feet into
smaller sections, so that the hydrostatic
pressure is felt only over the distance be-
tween any two valves. This is not true, how-
ever, when valves become incompetent.
Then the full effect of gravity is transmitted
Fig. 8-6. Effect of Gravity on Venous Pressure
(A) The hydrostatic pressure of blood due to
gravity for a person standing quietly is shown
to be a positive value in veins below the heart
and a negative value in veins above the heart.
Accordingly, in a foot vein 80 cm below the
heart pressure will equal +80 cm of water,
whereas in a hand held 40 cm above the heart,
venous pressure will equal -40 cm of water. (B)
Venous pressures at the ankle are compared
for a person lying, standing quietly, or running.
Note that during running skeletal muscle con-
traction squeezes veins, which pumps blood
from the ankle against the force of gravity to-
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 in the legs, which lack support from
surrounding musculature. Such incompe-
tent veins are called varicose veins.
(3) Most deep veins are surrounded by
skeletal muscle, and as muscles contract,
veins are squeezed and blood is milked
from one valve past the next toward the
heart. Lack of muscle contraction - as for
soldiers standing at attention - may lead to
peripheral venous pooling and fainting, es-
pecially in hot weather.

37
4. Importance of Inspiration
on Venous Return (and Car- A InspirationChest wall
diac Output) 4 5
Negative intrathoracic Pulmonic valve closure
pressure distends delayed (physiologic
splitting of second heart
Another important factor aiding venous re- pulmonary vessels and
decreases venous return
to the left atrium
Lung sound)

turn is inspiration (Fig. 8-7). During inspira- 3

tion the intrapleural (or intrathoracic) pres- Negative intrathoracic

pressure sucks venous
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
more blood into the right atrium. Because pressure forces blood in
vena cava toward right Tissues
intra-abdominal pressure

atrium

the downward movement of the dia-

Capillaries
phragm increases intra-abdominal pres- B Inspiration Expiration
sure, vessels in the abdominal cavity are Intrathoracic pressure
Right ventricular stroke volume
Decreased
Increased
Increased
Decreased
Thoracic blood volume Increased Decreased
Left ventricular stroke volume Decreased Increased
compressed, which simultaneously forces
blood toward the heart. It is noteworthy Fig. 8-7. P. Eggena,
The Physiological Basis of Primary Care, Novateur Medmedia

Fig. 8-7. Effects of Respiration on Venous Re-

that some patients in hemorrhagic shock,
who suffer from a decreased venous re-
turn, are found to have intense constriction
of the abdominal muscles, which would
tend to facilitate venous return.
turn and Cardiac Output. (A) The sequence of
events (1) thru (5) occur during inspiration. (B)
Effects of inspiration and expiration on intratho-
racic pressure, thoracic blood volume, and right
or left ventricular stroke volumes are listed.

While a deep inspiration increases venous

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

38
Bainbridge reflex. This reflex is initiated
when the atrium is stretched. Afferent im-
pulses are carried over vagal fibers to the
medulla and result in decreased parasym-
pathetic and increased sympathetic stimu-
lation of the SA node and atrial muscle.
This reflex moves blood out of the atrium
and into the ventricle.
While inspiration facilitates venous return
to the heart, an increased (positive) intra-
thoracic pressure during a forced expira-
tion impedes venous return. This is why a
trumpet player has a red face and dis-
tended neck veins. Blood will not drain
from the neck and face into the right
atrium as long as these structures are com-
pressed. This is, in part, why patients with
prolonged and repeated coughing spells
may faint. The continued positive intratho-
racic pressure during the coughing epi-
sodes prevents venous return and dimin-
ishes cardiac output. Patients on positive
pressure ventilators, especially when the
ventilator is set for PEEP (i.e., positive
end-expiratory pressure), experience a
decrease in venous return and in cardiac
output. It is, therefore, important to weigh
the potential benefits of using PEEP (e.g.,
increased arterial oxygen tension of blood)
against a diminished cardiac output and
decreased delivery of oxygenated blood to
tissues. We sometimes seem to forget that
life is not divided into inspiration and expi-
ration but that there are relatively long peri-
ods of time between breathing in or out. It
is in these long intervals between breaths
that intrathoracic pressure is normally
slightly subatmospheric (e.g.,-2 mmHg).
This is also true for patients on positive
pressure ventilators, unless the ventilator
has been set for continuous positive air-
way pressure (CPAP).
Important changes in venous return, car-
diac output, and blood pressure are ob-
served in breathholding and straining dur-
ing the Valsalva maneuver (Fig.8-8). Dur-
ing the Valsalva maneuver, a person takes
in a deep breath, then exhales forcefully
against a closed glottis. This may increase
intrathoracic pressure, for example, from
-2 to +40 mmHg. Because the aorta and
large arteries in the chest are exposed to
this additional 42 mmHg, blood pressure in
the brachial artery rises by an extra 42
mmHg and then falls gradually, as venous
return to the right and left ventricles de-
clines and cardiac output decreases. The
decrease in blood pressure initiates the ba-
roreceptor reflex, which causes heart rate
and peripheral vascular resistance to in-
crease. This results in a small increase in
blood pressure toward the end of the pe-
riod of straining, which is an inadequate
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 autonomic
nervous system). 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
on Venous Return (and Car-
diac Output)
Finally, an important factor in regulating ve-
nous return is the extent to which the veins
are filled with blood. It is not just the blood
volume that is important, but the relation-
ship between the amount of blood and the
compliance of the veins (e.g., their sympa-
thetic tone), because it is ultimately the ve-
nous pressure that moves blood toward
the heart. This force, which is generated
by veins as they contract around the vol-
ume of blood they hold, is sometimes re-
ferred to as vis a tergo. Also contributing
to this force is the pressure transmitted
through the capillaries by blood pumped
into arteries. Of course the volume of
blood and the pressure in veins changes
constantly as blood flows continuously
into veins from capillaries on one end and
is pumped out by the right ventricle on the
other end. Therefore, the resting recoil
pressures of veins and arteries can only be
measured when no blood is flowing, i.e.,
when the heart has stopped. We observed
such resting recoil pressures upon stop-
ping the heart in an anesthetized dog (Fig.
8-9). Stimulating the animal's right vagus
with an electrical impulse caused sinus ar-
rest (note the absence of P waves on the
ECG tracing in the bottom panel), followed
by a series of ventricular escape beats
(note the large, wide QRS complexes). As
the heart stopped beating, the femoral ar-
tery blood pressure decreased to a basal
value of approximately 10 mmHg (middle
panel) and pulmonary artery pressure
equilibrated at a similar level, i.e., at about
the level of the PAWP (top panel). These
observations indicated that, in the absence
of the heart's pumping action, blood sim-
ply flows down its pressure gradient from
arteries into veins until all pressures in the
circulation are equal. This equilibrium pres-
sure is called the mean circulatory filling
pressure. In the experiment in Fig.8-9, the
mean circulatory filling pressure is about
equal to the pulmonary artery wedge pres-
sure, or about 10 mmHg (A).
When the electrical stimulus was removed
from the vagus (B), systemic blood pres-
sure returned over a period of five beats to
normal (C). The sequence of events respon-
sible for returning the dog's blood pres-
sure to normal is shown in human terms in
Figure 8-10. In this model of the peripheral
circulation, we will assume that the periph-
eral vascular resistance is 20 mmHg/L/
min.
During vagal stimulation at point A (Figs.
8-9, 8-10), cardiac output was 0 L/min and
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 mean arterial
pressure 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 vagus nerve 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
stimulation caused a sino-atrial block with an ideov-
the heart. The other portion of the stroke
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
close to the wedge pressure (PAWP) (A). When va-
arteries had to be first stretched to a point
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:
CO= (105 - 5) mmHg/ 20 (mmHg/ L/
min) = 5 L/min
In other words, once the large arteries had
been primed with their usual blood vol-
ume, blood again moved around the circu-
lation at a rate of 5 L/min, which is the nor-
mal resting value for both cardiac output
Fig. 8-10. Model of the Circulation. The circula-
tory system is modeled after the experiment de-
picted in Figure 8-9. Assuming a total periph-
eral resistance of 20 mmHg/L/min, cardiac out-
put (CO) is 0 L/min (A) when the systemic
mean arterial pressure (SMAP) and central ve-
nous pressure (CVP) are both 10 mmHg; CO is
1 L/min (B) when SMAP rises to 29 mmHg and
CVP falls to 9 mmHg; and CO is 5 L/min (C)
when SMAP rises to 105 mmHg and CVP falls
to 5 mmHg.

and venous return.

to be. We could make a graph that shows

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

curve, 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
shifted to the left with a decrease in MCFP.
cause the venous return curve to shift to
(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
MCFP.
patients with right ventricular failure

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

Fig. 8-12. Cardiac Output and Venous Re-
turn Curves. Cardiac output and venous re-
turn curves from Figures 8-4 and 8-11A
have been combined into a single graph.
Note that cardiac output must equal venous
return (when measured for more than a few
beats), so that the circulation will stabilize at
points of intersection between the venous
return and cardiac output curves. That equi-
librium point is normally at a cardiac output
(or venous return) of 5 L/min and a CVP of 5
mmHg (or PAWP of 10 mmHg).
We can now combine the curves for car-
diac output and venous return as a func-
tion of CVP (or PAWP) into a single graph
(Fig. 8-12). Similar graphs have been em-
ployed by Guyton, who used right atrial
pressure as the independent variable, to
analyze the relationship between cardiac
output and venous return in a variety of
common physiological as well as clinical
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.
1. Graphic Analysis of Exer-
cise
Point A on the graph in Figure 8-13 repre-
sents a person at rest with a cardiac out-
put of 5 liters/min and a CVP of 5 mmHg.
As he anticipates exertion, sympathetic
cholinergic nerves cause vasodilation in
skeletal muscle and a decrease in the total
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-
ward rather than shifted in parallel to the
left, so that the MCFP (i.e., the pressure
when cardiac output and venous return are
0 liters/min) has not changed. As a conse-
quence of this decrease in total peripheral
resistance, and a relatively normal heart
cannot handle the excessive load (high
output failure). A good example of high
49
Fig. 8-13. Cardiac Function Curves during Exer-
cise. Cardiac output and venous return have
been plotted as a function of CVP. Anticipation of
exercise decreases total peripheral resistance
and thereby causes upward rotation of the ve-
nous return curve to a new equilibrium point B.
Further dilation of muscle arterioles during exer-
cise rotates the venous return curve further up-
ward to point C. Sympathetic stimulation of the
heart increases myocardial contractility and heart
rate, causing an upward (and leftward) shift of
the cardiac output curve to the final equilibrium
point D. At point D, cardiac output and venous re-
turn are twice the resting values (A), with only a
minimal increase in PAWP (or CVP).
cardiac output failure was a 95 year-old
man with severe anemia. Let us assume
that he was at point A in figure 8-14 when
he was not anemic. As his hemoglobin con-
centration gradually fell from 15 gm/dL to
Fig. 8-14. High Cardiac Output Failure in Severe
Anemia.
Cardiac output and venous return have been plot-
ted as a function of CVP (or PAWP) in a case of
severe anemia. As the anemia increases in sever-
ity, the total peripheral resistance progressively
decreases and the venous return curve rotates
upward and to the right, resulting in an increase
in cardiac output from A to B to C. The increase
in cardiac output is associated with a significant
increase in CVP and in PAWP, causing symp-
toms of peripheral edema and congestive heart
failure, respectively.
less than 7 gm/dL, his total peripheral resis-
tance gradually decreased, presumably
due to a combination of a diminished
blood viscosity and release of vasodilator
substances from hypoxic tissues. His car-
diac output increased progressively from A
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
return, i.e., circulatory shock, or from
pump failure, i.e., cardiogenic shock (Fig.
8-15). Note that in circulatory shock CVP
and PAWP are decreased; whereas, in car-
diogenic shock these pressures are in-
creased.
A. Circulatory Shock
Fig. 8-15. Circulatory and Cardiogenic Shock.
Cardiac output and venous return curves have
been plotted as a function of CVP or PAWP for
right or left ventricles, respectively. The fall in car-
diac output in circulatory shock is caused by a
downward shift in the venous return curve,
whereas the fall in cardiac output in cardiogenic
shock is caused by a downward shift in the car-
diac output curve.
Note that CVP (or PAWP) is low in circulatory
shock, but high in cardiogenic shock.

Circulatory shock may result from a de-

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

51

Fig. 8-16. Hemorrhagic Shock. Cardiac output
and venous return curves are plotted for a pa-
tient, Michelle, with internal bleeding from a
ruptured spleen. Initial blood loss resulted in a
downward depression of the venous return
curve and a shift in the equilibrium point from
A to B. Compensation occurred by sympa-
thetic stimulation of the heart, making it con-
tract more rapidly and more forcefully, and by
venoconstriction. This shifted the equilibrium
point from B to C, where both the venous re-
turn and cardiac output curves were raised.
Cardiac output fell subsequently, however,
from C to D, as sympathetic arteriolar constric-
tion rotated the venous return curve down-
ward. Michelle was admitted to the hospital in
this state of shock and was treated with intrave-
nous 0.9% NaCl, which shifted the venous re-
turn curve upward and the equilibrium point
from D to E.
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 vasoconstriction (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
to maintain blood pressure as high as pos-
sible in order to perfuse the most vital or-
gans - the brain and the heart. In other
words, the reduction in cardiac output was
more than offset by the increase in total pe-
ripheral resistance, so that blood pressure
increased (BP = CO x TPR).
The intense vasoconstriction lowered capil-
lary blood pressure, which facilitated reab-
sorption of fluids from the interstitium. As
this fluid was slowly added to plasma, the
venous return curve shifted to the right. To
continue to increase plasma volume and
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
curves in Figure 8-17 reconstruct the se-
quence of events that took place immedi-
ately following the heart attack.
As his left ventricle was injured as a result
of the coronary occlusion, his cardiac out-
put curve decreased and he stabilized at a
new equilibrium point B, where cardiac out-
put was reduced and pulmonary artery
wedge pressure increased. The fall in
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-
ated the compensatory responses, which
we have already considered in hemor-
rhagic shock. Briefly, sympathetic outflow
tenses capacitance vessels, which shifts
the venous return curve to the right (point
Fig. 8-17. Compensated Heart Failure. Car-
diac output and venous return curves for Mr.
M. Following a myocardial infarction, cardiac
output dropped to a lower function curve and
the equilibrium point moved from A to B. Com-
pensation occurred by venoconstriction and
mobilization of fluids from the interstitium, shift-
ing the equilibrium to point C. Increased sym-
pathetic stimulation of the heart, in turn, raised
cardiac output to a higher function curve so
that complete compensation (normal cardiac
output at rest) was obtained at point D. At
point D the PAWP is elevated above normal,
and the cardiac reserve is diminished.
C). This action, aimed at increasing cardiac
output, is reserve, which he lost and which
he needed when he had to exert himself.
He was not normal in another important re-
spect. His pulmonary artery wedge pres-
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
a minimum cardiac output for sustaining
tissue metabolism at rest (about 5 L/min).
Although the heart is once again bom-
barded with sympathetic stimuli, it has
been stimulated for too long and norepi-
nephrine receptors have been down-
regulated. The kidney, however, attempts
to compensate for the reduced cardiac out-
put by retaining more salt and water (this is
mediated, as usual, by sympathetic stim-
uli, vasopressin, and aldosterone). Al-
though renal compensation usually works
well with a normal or near-normal heart,
this strategy becomes counterproductive
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
G. Not only is the increased venous return
not increasing cardiac output, but the pul-
Fig. 8-18. Decompensated Heart Failure.
Cardiac output and venous return curves are
shown for Mr. M after he had compensated
for a myocardial infarct (Fig. 8-17,D). He
then develops atrial fibrillation and moves to
a lower cardiac function curve and a new
equilibrium point C. His heart is incapable of
compensating by moving to a higher cardiac
function curve with sympathetic stimulation,
but his kidneys function normally and retain
more salt and water, causing the venous re-
turn curve to shift progressively to the right
from C to F to G.
Note that the cardiac output curve is flat, so
that these shifts in the venous return curve
do not increase cardiac output to the mini-
mum requirement of 5 L/min (at rest). Moreo-
ver, as PAWP exceeds a value of about 27
mmHg, pulmonary edema develops.
monary artery wedge pressure is continu-
ously rising and the lungs are being pro-
gressively flooded with more and more

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

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 preload 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,
atrial and aortic pressures during a car-
diac cycle for a healthy person and for
Mr. Bach who has aortic insufficiency.
5. To the graph above (4) add the mur-
murs of aortic insufficiency and the Aus-
tin Flint murmur and explain their ori-
gins.
14. Why do patients with congestive heart
failure complain of nocturia?
15. Why is the renal filtration fraction in-
creased when cardiac output declines?
16. How do kidneys retain more salt and
water in congestive heart failure?
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. Hemodynamics
Episode 2. Regulation of the Circulation
Episode 3. Cardiac Output and Venous Return