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Faculty of Medicine
Universitas Padjadjaran
Semester : 5
System : Cardiovascular
Week theme : Myocardium
Trigger case : Heart failure and cardiogenic shock (SKDI competency level 3B)
Differential diagnoses: Cardiomyopathy (2)

Week schedule : Three meetings

Pacing and sequencing: First meeting: page 1-3
Second meeting: Discussion, page 4-epilogue
Third meeting: Discussion

Learning objectives :

At the end of the week the student should be able to:

1. Describe the topography of the heart (surfaces, borders and layers of heart )
2. Mention chambers of the heart and interior chambers of the heart (review)
3. Describe the projection of the heart to the anterior thoracic wall (apex, base & ictus
4. Explain the histology of myocardial cells, explain short term adaptive mechanisms,
explain molecular mechanisms myocardial remodeling and failure, and chronic
myocardial remodeling
5. The student will be able to explain Cardiac cycle and regulation of the heart
- explain the medical physics of pressure, flow, and resistance
- explain the physical characteristics of the circulation.
- explain the basic theory of the circulation function.
- explain the interrelationship among pressure, flow, and resistance.
- explain the dynamics of the circulation in cardiac failure
- explain about the unilateral left heart failure
- explain what is low-output cardiac failure-cardiogenic shock
- explain the mechanism of edema in patient with cardiac failure
- explain what is the cardiac reserve
- Illustrate the physiologic causes of shock
- Give some example types of shock.
6. Explain cardiac output, preload, afterload, venous return, cardiac remodelling,
7. Cardiac contractility,adaptive mechanism, neurohormonal ajustment ( C3)
8. explain the mechanism of circulation control
- explain the local control of blood flow in response to tissue needs
- explain the mechanism of blood flow control.
- explain the mechanism of humoral regulation of the circulation.
- explain the mechanism of nervous regulation of the circulation.
- explain the role of the nervous system for rapid control of arterial pressure
- explain the special feature of nervous control of arterial pressure
- explain the function of the renal body fluid system for arterial pressure
explain the effect of the rennin angiotensin system
- Illustrate the Cardiac output, venous return
- explain the normal value for cardiac output at rest and during activity
- explain the control of cardiac output by venous return- role of the Frank-
Starling mechanism of the heart.
- explain what are the pathologically high and pathologically low cardiac
- explain the quantitative analysis of cardiac output regulation
- explain the method of measuring cardiac output
- Describe molecular mechanisms myocardial remodeling and failure, and
chronic myocardial remodeling
9. Understand the pathogenesis and histopathologic changes of cardiac hypertrophy,
dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy
and myocarditis in heart failure.
10. Describe the pathophysiology of diastolic heart failure
11. Define the definition of heart failure
12. Describe the forms, symptoms and sign of heart failure, respiratory distress,
reduced exercise capacity, and other symptoms
13. Describe the physical and laboratory findings: the blood
14. Describe the normal chest roentgenogram and heart failure chest roentgenogram
15. Analyze by categorizing the prognosis of heart failure
16. Analyze the management of acute, new onset, and chronic heart failure
17. Analyze the management of pharmacological therapy of chronic heart failure
caused by systolic dysfunction and diastolic dysfunction and adjunctive
pharmacological therapy
18. Explain the Drug used in the treatment of heart failure: Concept of mechanism of
Action of certain drugs (Digoxin, Captopril, Furosemid,Isosorbid Dinitrat)
19. Adverse Effect of digoxin(arrhytmias),captopril (cough), furosemid (hypokalemic
metabolic alkalosis,ototoxicity,hyperuricemia,hypomagnesia), Isosorbid dinitrat
(orthostatic hypotension)
20. Drug used in cardiogenik syok (dobutamin,dopamin, ephedrine, ephinephrine,
21. Concept of mechanism of Action of certain drugs (dobutamin,dopamin, ephedrine,
ephinephrine, norepinephrinee) Adverse Effect
22. Describe the pathophysiology and pathogenesis of pulmonary edema, mention the
differential diagnosis of pulmonary edema,and explain the management of
pulmonary edema.
23. Describe the cardiogenic shock
24. Describe in brief about cardiomyopathy
25. CRP: Explain the epidemiology of heart failure
26. Medical rehabilitation: To understand the promotion intervention of Physical
Medicine and Rehabilitation and the prevention the complication of
immobilization/inactivity caused by cardiac failure.
27. BHP: Evaluate the issue of quality of life in patient with heart failure
28. PHOP: Explain the primary and secondary prevention of Heart Failure, explain the
education in heart failure patient (diet and exercise)

Atherosclerosi Pathogenesis


Compensatory mechanism

Anatomy and histology Myocardiac

of myocardium

Decompensatory mechanism


Physiology of
heart muscle Contractility
contraction and
cardiac cycle

Cardiac Sympathetic
Right Left HF output ↓ activation ↑
Preload ↑
End diastolic overwork Heart Rate ↑
pressure ↑
Some blood cannot
enter ventricle Over- Cardiac
stretched wall enlargement

Pulmonary edema

JVP ↑ Hepatomegaly Hydrostatic Rales Physiology of:

pressure ↑
Cardiac output
Case Synopsis
Dyspnea Regulation of heart pump

Pretibial edema Physiology of: Anatomy of heart

Frank-Starling Mechanism topography

Page 1

You were the doctor on duty at Emergency Unit when Mrs. H, a 58 year-old woman was
Mrs. H was admitted to the ER because of shortness of breath.

History of illness
She was known to have hypertension since 10 years ago and last year had been
hospitalized twice due to high blood pressure and shortness of breath. Since then she had
been seeing the doctor and take the pills, but not on a regular basis. For the last two years
she had been noticing some grade of shortness of breath when climbing 1 flight of stairs
where her office is located or walking uphill and had been frequently woken at night due to
shortness of breath. These conditions became progressively worse until she was breathless
even at rest. Since two days before admitted to hospital, the shortness of breath was

1. Identify the patient’s problems
2. Generate a list of hypotheses for each problem
3. What further information from Mrs. H that you need?

Page 2

Physical examination

BMI : 28 kg/m2
Height : 158 cm Weight : 70 kg
Blood pressure : 150/100 mmHg Pulse : 110
bpm and regular
Respiration : 36/min Temperature : 370C.
Neck : Jugular Venous Pressure (5+4) cm H2O
Lung : Rales could be heard throughout both lungs
Heart : Point of maximum impulse was felt 2cm lateral of left midclavicular line
ICS VI. The first and second heart sounds were soft. There were an S3 gallop and a
moderate grade (2/6) holosystolic murmur heard at the apex
Abdomen : Soft. The liver was felt 3 cm below the costal margin. No spleen or other
masses was palpable
Extremities : Pretibial pitting edema
Neurological exams: No significant findings

1. Identify the additional problems
2. Summarized the hypotheses for each problem
3. What further information from Mrs. H may be helpful?


1. Patient’s Problem :
- History of chest discomfort
- Shortness of breath (cardiac and non cardiac origin (pulmo, renal)
- Paroxysmal nocturnal dyspnea
- Hepatomegaly and pretibial pitting edema

2. Hypotheses
- Chest Discomfort
- Cardiac (Heart Failure)
- Pulmonary problem
- Angina equivalent
- Liver disease, renal and cardiac problem

3. Further information from Mrs H ?

- Functional class heart failure from NYHA (New York Heart Association)
- Chest x-ray and ECG
- Laboratory examination : SGOT/SGPT, Ureum kreatianin, CBC, Electrolyte ion (NA+,
K+) Blood gas analysis, Lipid profile, Blood glucose,

Guiding questions for tutors to focus on

The students are supposed to test the hypothesis of those problems, such as
1. State the various causes and types of heart failure
2. Explain the pathogenic basis for LV remodeling
3. Describe the process underlying apoptosis as opposed to necrosis
4. Explain the autocrine and paracrine interactions in heart failure
5. Explain the sequence of events from coronary heart disease to heart failure
6. Describe the natural history of chronic heart failure
7. What is the definition of acute heart failure ? What are their classifications?
8. What are the precipitation factors of acute heart failure?
9. Explain the heart ability to adapt the acute and long lasting altered hemodynamic load
10. Explain the relationship between phenotypic alteration of the heart cells and
the change of heart properties
11. Describes the alteration of the genes expression in cardiac overload that adjust
the heart to the new demands
12. List the characteristic of the cellular constituents of myofibril, sarcoplasmic,
extracellular matrix, plasma membrane, sarcoplasmic enzyme in cardiac overload
13. Describe the process of the recognition from mechanical work until the action
of biochemical effectors that stimulates the change of genes expression (include signal into
cytoplasmic message)

Page 3

Chest x ray:
The heart was enlarged with signs of pulmonary congestion and a blunted right costo-
phrenic angle was detected

ECG: Her electrocardiogram showed sinus tachycardia with sign of left ventricle

Laboratory Examination:
Hb : 12 gr % WBC : 8500/mm3
LDL : 110 mg/dL, HDL : 35 mg/dL , Cholesterol total : 220 mg/dL, triglyceride :
Random blood sugar: 192 mg/dl

SGOT : 22 IU/dl
SGPT: 26 IU/dl
Ureum :64 mg/dl
Creatinin : 0.95 mg/dl
HCO3- = 16 mEq/L
Na+ = 137 mEq/L
K+ = 3,8mEq/L

A dilated LV with thickened inter ventricular septum (IVS) and posterior wall (PW). The
EF is around 45%. No regional wall motion abnormalities . A moderate degree of MR is

1. How does this information change your hypothesis?
2. Identify the patient’s problems!
3. Explain the significance of the laboratory, chest x-ray, ECG and echocardiography
4. What have you learned so far?
5. What are your management plans for her?

Guiding questions for tutors to focus on

The students should at least discuss problem such as
1. Why did she have exertion dyspnea?
2. What is the mechanism behind orthopnea?
3. What is the cause of nocturia?
4. What is the significance of S3 gallop?
5. Why she had moderate cardiomegaly with the costophrenic angles on chest x ray?
6. What are the underlying cardiac causes of heart failure?

Page 4

She was diagnosed as hypertensive heart disease, mitral regurgitation, heart failure New
York Heart Association Class IV
She was given Oxygen, IV line and furosemide injection, and oral treatment: captopril,
Kalium Slow release agent.
During the second day the patient felt more breathless, cold sensation in extremities and

Physical examination revealed: Blood pressure 85/60 mmHg, HR 140 bpm/mnt, RR:

1. How does this information change your hypothesis?
2. Identify the patient’s problems!
3. What are your management plans for her?
4. When should we give the program of Physical Medicine and Rehabilitation in
cardiac failure patient?
5. What should we concern in giving training exercise for cardiac failure patient?

Guiding questions for tutors to focus on

1. Explain the underlying basis for abnormalities in blood gas during heart failure.
2. What are the risk factors of heart failure?
3. What is the significance of an echocardiographic assessment in heart failure?
4. Explain the frontline treatment for acute heart failure.
5. Explain the frontline treatment for chronic heart failure.
6. Explain the preventive measures to slow the disease process.
7. State the therapeutic options for intractable heart failure.
8. Describe the mechanism of action, effect, adverse reaction, pharmacokinetics,
contraindication of digoxin in treatment of heart failure
9. Describe the role of furosemide, Captopril, and slow release potassium chloride used
in treatment in heart failure
10. What is the cause of the patient has got that shock condition?
11. When and why should we give the program of Physical Medicine and
Rehabilitation in cardiac failure patie
Page 5

She was diagnosed as cardiogenic shock she was given dobutamin injection and referred to
intensive cardiac care unit.

1. What is cardiogenic shock?

2. Describe the mechanism of cardiogenic shock?
3. Describe the MOA, effect, adverse reaction, pharmacokinetics of dobutamin.
She was hospitalized for one week in ICCU, and discharged 3 days after. She had to have
regularly check up. She was advised to move her office to the first floor. Medication :
Captopril, Bisoprolol, Furosemide.

1. BHP: Evaluate the issue of quality of life in patient with heart failure
2. How is the prevention (primary and secondary) of Heart Failure? Educate the patient
about diet and exercise!
3. When should a HF patient given Digoxin and Spironolactone?
4. Captopril :
5. Bisoprolol :
6. Digoxin :
7. Spironolactone :


Anatomy Department
Learning Objective :
1. Describe the topography of the heart (surfaces, borders and layers of heart )
2. Mention chambers of the heart and interior chambers of the heart

Topography of the heart

The heart, slightly larger than a clenched fist, is a double, self-adjusting, suction and
pressure pump, the parts of which work in unison to propel blood to all parts of the body.

The right side of the heart (right heart) receives poorly oxygenated (venous) blood from the
body through the SVC and IVC and pumps it through the pulmonary trunk to the lungs for
oxygenation (Fig. 1.39A). The left side of the heart (left heart) receives well-oxygenated
(arterial) blood from the lungs through the pulmonary veins and pumps it into the aorta for
distribution to the body.

The heart has four chambers: right and left atria and right and left ventricles. The atria are
receiving chambers that pump blood into the ventricles (the discharging chambers). The
synchronous pumping actions of the heart's two atrioventricular (AV) pumps (right and left
chambers) constitute the cardiac cycle (Fig. 1.39B). The cycle begins with a period of
ventricular elongation and filling (diastole) and ends with a period of ventricular
shortening and emptying (systole). Two heart sounds are heard with a stethoscope: a lub
sound as the blood is transferred (sucked) from the atria into the ventricles and a dub sound
as the ventricles expel blood from the heart. The heart sounds are produced by the
snapping shut of the oneway valves that normally keep blood from flowing backward
during contractions of the heart

I. Surfaces :
1. Diaphragmatic ( inferior)
2. Sternocostal (anterior)
3. Right & left pulmonary (lateral)
4. Base ( posterior)
5. Apeks
II. Borders :
1. Right
2. Left
3. Inferior
4. Superior

III. Layers of heart chamber :

1. Endocardium
2. Myocardium
3. Epicardium

IV.Chambers of the heart :

1. Right atrium
2. Left atrium
3. Right ventricle
4. Left ventricle

V. Interior chambers of the heart :

1. Right atrium with right auricle :
a. Sinus venarum :
 smooth
 Opening of superior & inferior venae cavae, coronary sinus
b. M. pectinate :
 Rough
c. Sulcus terminalis ( Crista terminalis )
d. Interatrial septum :
 oval fossa ( fetus : oval foramen)

2. Left atrium with left auricle

a. Sinus venarum :
 Smooth
 Opening of four pulmonary veins
two superior
two inferior

b. M. pectinate :
 Rough

3. Right Ventricle
a. Conus arteriosus (infundibulum)
 Smooth
 Opening to pulmonary trunk
 At the apex : pulmonary valve (semilunar valve) :
Right cusp
Left cusp
Anterior cusp

b. Trabeculae carnae
 Rough
c. Supraventricular crest
d. Right AV (tricuspid) :
 orifice
 tricuspid valve : anterior, posterior and septal cusps
 M. papilary : anterior, posterior, septal
 Tendinous cords
e. Interventricular septum :
 muscular part :
septomarginal trabeculae (moderator band) :
right branch of the AV bundle
 membranous part
4. Left Ventricle
a. Conus arteriosus (infundibulum)
 Smooth
 Opening to aorta (aortic vestibule)
 At the apex : aortic valve (semilunar valve) :
Right cusp :
right aortic sinus –right coronary a.
Left cusp :
left aortic sinus –left coronary a.
Posterior cusp:
posterior aortic sinus-non coronary

each of cusp has : nodule and lunule

b. Trabeculae carnae
 Rough
c. Left AV (bicuspid) :
 orifice
 bicuspis valve : anterior and posterior cusps
 M. papilary : anterior, posterior
 Tendinous cords

Cardiac Muscle—Myocardium
Like the skeletal musculature, the heart muscle tissue is striated. In contrast to skeletal
muscles, cardiac muscle fibers are branched and anastomose with each other, thus creating
a network. Cardiac muscle fibers are thinner than skeletal muscle fibers but thicker than
smooth muscle cells. Heart muscle cells (cardiomyocytes) have only one nucleus.
Characteristic of cardiomyocytes are struts (disci intercalares),which are dense, heavily
stained bands across the muscle fibers.

Cardiac Muscle—Purkinje Fibers

Apart from the labor musculature, the myocardium also contains specific muscle fibers for
the excitation and conduction of excitatory states; among these are the cells of the
atrioventricular system, the Purkinje fibers. They stand out because they are usually much
thicker than the fibers of the labor musculature. These specific myocytes have significantly
more sarcoplasm
and fewer This figure shows numerous subendocardial Purkinje fibers
(cardiac conducting cells) with loose connective tissue between them.

Physiology Department
1. Cardiac cycle and regulation of the heart pump

Overview of the Circulation; Medical Physics of Pressure, Flow, and Resistance

The function of the circulation is to service the needs of the body tissues to transport
nutrients to the body tissues, to transport waste products away, to conduct hormones from
one part of the body to another, and, in general, to maintain an appropriate environment in
all the tissue fluids of the body for optimal survival and function of the cells.
The rate of blood flow through most tissues is controlled in response to tissue need for
nutrients. The heart and circulation in turn are controlled to provide the necessary cardiac
output and arterial pres- sure to cause the needed tissue blood flow.

Functional Parts of the Circulation.

The function of the arteries is to transport blood under high pressure to the tissues. For this
reason, the arteries have strong vascular walls, and blood flows at a high velocity in the
The arterioles are the last small branches of the arterial system; they act as control conduits
through which blood is released into the capillaries. The arte- riole has a strong muscular
wall that can close the arteriole completely or can, by relaxing, dilate it several fold, thus
having the capability of vastly altering blood flow in each tissue bed in response to the
need of the tissue.
The function of the capillaries is to exchange fluid, nutrients, electrolytes, hormones, and
other substances between the blood and the interstitial fluid. To serve this role, the
capillary walls are very thin and have numerous minute capillary pores permeable to water
and other small molecular substances.
The venules collect blood from the capillaries, and they gradually coalesce into
progressively larger veins.
The veins function as conduits for transport of blood from the venules back to the heart;
equally important, they serve as a major reservoir of extra blood. Because the pressure in
the venous system is very low, the venous walls are thin. Even so, they are muscular
enough to contract or expand and thereby act as a controllable reservoir for the extra blood,
either a small or a large amount, depending on the needs of the circulation.

Physical Characteristics of the Circulation

The circulation, shown in Figure 14–1, is divided into the systemic circulation and the
pulmonary circulation. Because the systemic circulation supplies blood flow to all the
tissues of the body except the lungs, it is also called the greater circulation or peripheral

Volumes of Blood in the Different Parts of the Circulation.

Figure 14–1 gives an overview of the circulation and lists the percentage of the total blood
volume in major segments of the circulation.

For instance, about 84 per cent of the entire blood volume of the body is in the systemic
circulation, and 16 per cent in heart and lungs. Of the 84 per cent in the systemic
circulation, 64 per cent is in the veins, 13 per cent in the arteries, and 7 per cent in the
systemic arterioles and capillaries. The heart contains 7 per cent of the blood, and the
pulmonary vessels, 9 per cent.
Most surprising is the low blood volume in the capillaries. It is here, however, that the
most important function of the circulation occurs, diffusion of sub- stances back and forth
between the blood and the tissues.

Cross-Sectional Areas and Velocities of Blood Flow. If all the systemic vessels of each
type were put side by side, their approximate total cross-sectional areas for the average
human being would be as follows:
Note particularly the much larger cross-sectional areas of the veins than of the arteries,
averaging about four times those of the corresponding arteries. This explains the large
storage of blood in the venous system in comparison with the arterial system.
Because the same volume of blood must flow through each segment of the circulation each
minute, the velocity of blood flow is inversely proportional to vascular cross-sectional
area. Thus, under resting conditions, the velocity averages about 33 cm/sec in the aorta but
only 1/1000 as rapidly in the capillaries, about 0.3 mm/sec. However, because the
capillaries have a typical length of only 0.3 to 1 millimeter, the blood remains in the
capillaries for only 1 to 3 seconds. This short time is surprising because all diffusion of
nutrient food substances and electrolytes that occurs through the capillary walls must do so
in this exceedingly short time.

Pressures in the Various Portions of the Circulation. Because the heart pumps blood
continually into the aorta, the mean pressure in the aorta is high, averaging about 100 mm
Hg. Also, because heart pumping is pulsatile, the arterial pressure alternates between a
systolic pressure level of 120 mm Hg and a diastolic pressure level of 80 mm Hg, as shown
on the left side of Figure 14–2.
As the blood flows through the systemic circulation, its mean pressure falls progressively
to about 0 mm Hg by the time it reaches the termination of the venae cavae where they
empty into the right atrium of the heart.
The pressure in the systemic capillaries varies from as high as 35 mm Hg near the
arteriolar ends to as low as 10 mm Hg near the venous ends, but their average “functional”
pressure in most vascular beds is about 17 mm Hg, a pressure low enough that little of the
plasma leaks through the minute pores of the capillary walls, even though nutrients can
diffuse easily through these same pores to the outlying tissue cells.
Note at the far right side of Figure 14–2 the respective pressures in the different parts of the
pulmonary circulation. In the pulmonary arteries, the pressure is pulsatile, just as in the
aorta, but the pressure level is far less: pulmonary artery systolic pressure averages about
25 mm Hg and diastolic pressure 8 mm Hg, with a mean pulmonary arterial pressure of
only 16 mm Hg. The mean pulmonary capillary pressure averages only 7 mm Hg. Yet the
total blood flow through the lungs each minute is the same as through the systemic
circulation. The low pressures of the pulmonary system are in accord with the needs of the
lungs, because all that is required is to expose the blood in the
pulmonary capillaries to oxygen and other gases in the pulmonary alveoli.

Basic Theory of Circulatory Function

Although the details of circulatory function are complex, there are three basic principles
that underlie all functions of the system.
1. The rate of blood flow to each tissue of the body is almost always precisely controlled
in relation to the tissue need. When tissues are active, they need greatly increased supply of
nutrients and therefore much more blood flow than when at rest—occasionally as much as
20 to 30 times the resting level. Yet the heart normally cannot increase its cardiac output
more than four to seven times greater than resting levels. Therefore, it is not possible
simply to increase blood flow everywhere in the body when a particular tissue demands
increased flow. Instead, the microvessels of each tissue continuously monitor tissue needs,
such as the availability of oxygen and other nutrients and the accumulation of carbon
dioxide and other tissue waste products, and these in turn act directly on the local blood
vessels, dilating or constricting them, to control local blood flow precisely to that level
required for the tissue activity. Also, nervous control of the circulation from the central
nervous system provides additional help in controlling tissue blood flow.

2. The cardiac output is controlled mainly by the sum of all the local tissue flows. When
blood flows through a tissue, it immediately returns by way of the veins to the heart. The
heart responds automatically to this increased inflow of blood by pumping it immediately
into the arteries from whence it had originally come. Thus, the heart acts as an automaton,
responding to the demands of the tissues. The heart, however, often needs help in the form
of special nerve signals to make it pump the required amounts of blood flow.

3. In general the arterial pressure is controlled independently of either local blood flow
control or cardiac output control. The circulatory system is provided with an extensive
system for controlling the arterial blood pressure. For instance, if at any time the pressure
falls significantly below the normal level of about 100 mm Hg, within seconds a barrage of
nervous reflexes elicits a series of circulatory changes to raise the pressure back toward
normal. The nervous signals especially (a) increase the force of heart pumping, (b) cause
contraction of the large venous reservoirs to provide more blood to the heart, and (c) cause
generalized constriction of most of the arterioles throughout the body so that more blood
accumulates in the large arteries to increase the arterial pressure. Then, over more
prolonged periods, hours and days, the kidneys play an additional major role in pressure
control both by secreting pressure-controlling hormones and by regulating the blood
Thus, in summary, the needs of the individual tissues are served specifically by the
circulation. In the remainder of this chapter, we begin to discuss the basic details of the
management of tissue blood flow and control of cardiac output and arterial pressure.

Interrelationships Among Pressure, Flow, and Resistance

Blood flow through a blood vessel is determined by two factors:
(1) pressure difference of the blood between the two ends of the vessel, also sometimes
called “pressure gradient” along the vessel, which is the force that pushes the blood
through the vessel, and
(2) the impediment to blood flow through the vessel, which is called vascular resistance.

Dynamics of the Circulation in Cardiac Failure

Acute Effects of Moderate Cardiac Failure
If a heart suddenly becomes severely damaged, such as by myocardial infarc- tion, the
pumping ability of the heart is immediately depressed. As a result, two main effects occur:
(1) reduced cardiac output
(2) damming of blood in the veins, resulting in increased venous pressure.
The progressive changes in heart pumping effectiveness at different times after an acute
myocardial infarction are shown graphically in Figure 22–1. The top curve of this figure
shows a normal cardiac output curve. Point A on this curve is the normal operating point,
showing a normal cardiac output under resting conditions of 5 L/min and a right atrial
pressure of 0 mm Hg.
Immediately after the heart becomes damaged, the cardiac output curve becomes greatly
lowered, falling to the lowest curve at the bottom of the graph. Within a few seconds, a
new circulatory state is established at point B rather than point A, illustrating that the
cardiac output has fallen to 2 L/min, about two-fifths normal, whereas the right atrial
pressure has risen to +4 mm Hg because venous blood returning to the heart from the body
is dammed up in the right atrium. This low cardiac output is still sufficient to sustain life
for perhaps a few hours, but it is likely to be associated with fainting. Fortunately, this
acute stage usually lasts for only a few seconds because sympathetic nerve reflexes occur
immediately and compensate, to a great extent, for the damaged heart, as follows.

Compensation for Acute Cardiac Failure by Sympathetic Nervous Reflexes. When the
cardiac output falls precariously low, many of the circulatory reflexes discussed in Chapter
18 are immediately activated. The best known of these is the baroreceptor reflex, which is
activated by diminished arterial pressure. It is probable that the chemoreceptor reflex, the
central nervous system ischemic response, and even reflexes that originate in the damaged
heart also contribute to activating the sympathetic nervous system. But whatever the
reflexes might be, the sympathetics become strongly stimulated within a few seconds, and
the parasympathetic nervous signals to the heart become reciprocally inhibited at the same
Strong sympathetic stimulation has two major effects on the circulation: first on the heart
itself, and second on the peripheral vasculature. If all the ventricular musculature is
diffusely damaged but is still functional, sympathetic stimulation strengthens this damaged
musculature. If part of the muscle is non- functional and part of it is still normal, the
normal muscle is strongly stimulated by sympathetic stimulation, in this way partially
compensating for the non- functional muscle. Thus, the heart, one way or another, becomes
a stronger pump. This effect is also demonstrated in Figure 22–1, showing after
sympathetic compensation about twofold elevation of the very low cardiac output curve.

Sympathetic stimulation also increases venous return because it increases the tone of most
of the blood vessels of the circulation, especially the veins, raising the mean systemic
filling pressure to 12 to 14 mm Hg, almost 100 per cent above normal. As discussed in
Chapter 20, this increased filling pressure greatly increases the tendency for blood to flow
from the veins back into the heart. Therefore, the damaged heart becomes primed with
more inflowing blood than usual, and the right atrial pressure rises still further, which helps
the heart to pump still larger quantities of blood. Thus, in Figure 22–1, the new circulatory
state is depicted by point C, showing a cardiac output of 4.2 L/min and a right atrial
pressure of 5 mm Hg.
The sympathetic reflexes become maximally developed in about 30 seconds. Therefore, a
person who has a sudden, moderate heart attack might experience nothing more than
cardiac pain and a few seconds of fainting. Shortly thereafter, with the aid of the
sympathetic reflex compensations, the cardiac output may return to a level adequate to
sustain the person if he or she remains quiet, although the pain might persist.

Chronic Stage of Failure—Fluid Retention Helps to Compensate Cardiac Output

After the first few minutes of an acute heart attack, a prolonged semi-chronic state begins,
characterized mainly by two events:
(1) retention of fluid by the kidneys and
(2) varying degrees of recovery of the heart itself over a period of weeks to months, as
illus- trated by the light green curve in Figure 22–1;

Renal Retention of Fluid and Increase in Blood Volume Occur for Hours to Days A
low cardiac output has a profound effect on renal function, sometimes causing anuria when
the cardiac output falls to one-half to two-thirds normal. In general, the urine output
remains reduced below normal as long as the cardiac output and arterial pres- sure remain
significantly less than normal, and urine output usually does not return all the way to
normal after an acute heart attack until the cardiac output and arterial pressure rise either
all the way back to normal or almost to normal.

Recovery of the Myocardium After Myocardial Infarction

After a heart becomes suddenly damaged as a result of myocardial infarction, the natural
reparative processes of the body begin immediately to help restore normal cardiac
function. For instance, a new collateral blood supply begins to penetrate the periph- eral
portions of the infarcted area of the heart, often causing much of the heart muscle in the
fringe areas to become functional again. Also, the undamaged portion of the heart
musculature hypertrophies, in this way offsetting much of the cardiac damage.
The degree of recovery depends on the type of cardiac damage, and it varies from no
recovery to almost complete recovery. After acute myocardial infarction, the heart
ordinarily recovers rapidly during the first few days and weeks and achieves most of its
final state of recovery within 5 to 7 weeks, although mild degrees of additional recovery
can continue for months.
Figure 22–1 shows function of the partially recovered heart a week or so after acute
myocardial infarction. By this time, considerable fluid has been retained in the body and
the tendency for venous return has increased markedly as well; therefore, the right atrial
pressure has risen even more. As a result, the state of the circulation is now changed from
point C to point D, which shows a normal cardiac output of 5 L/min but right atrial
pressure increased to 6 mm Hg. Because the cardiac output has returned to normal, renal
output of fluid also returns to normal, and no further fluid retention occurs, except that the
retention of fluid that has already occurred continues to maintain moderate excesses of
fluid. Therefore, except for the high right atrial pressure represented by point D in this
figure, the person now has essentially normal cardiovascular dynamics as long as he or she
remains at rest.
If the heart recovers to a significant extent and if adequate fluid volume has been retained,
the sympathetic stimulation gradually abates toward normal for the following reasons: The
partial recovery of the heart can elevate the cardiac output curve the same as sympathetic
stimulation can. Therefore, as the heart recovers even slightly, the fast pulse rate, cold skin,
and pallor resulting from sympathetic stimulation in the acute stage of cardiac failure
gradually disappear.

Physiologic Causes of Shock

Circulatory Shock Caused by Decreased Cardiac Output
Shock usually results from inadequate cardiac output. Therefore, any condition that
reduces the cardiac output far below normal will likely lead to circulatory shock. Two
types of factors can severely reduce cardiac output:
1. Cardiac abnormalities that decrease the ability of the heart to pump blood.
These include especially myocardial infarction but also toxic states of the heart, severe
heart valve dysfunction, heart arrhythmias, and other conditions. The circulatory shock that
results from diminished cardiac pumping ability is called cardiogenic shock. This is
discussed in detail in Chapter 22, where it is pointed out that as many as 85 per cent of
people who develop cardiogenic shock do not survive.

2. Factors that decrease venous return also decrease cardiac output because the heart
cannot pump blood that does not flow into it. The most common cause of decreased venous
return is diminished blood volume, but venous return can also be reduced as a result of
decreased vascular tone, especially of the venous blood reservoirs, or obstruction to blood
flow at some point in the circulation, especially in the venous return pathway to the heart.

Circulatory Shock That Occurs Without Diminished Cardiac Output

Occasionally, the cardiac output is normal or even greater than normal, yet the person is in
circulatory shock. This can result from (
1) excessive metabolism of the body, so that even a normal cardiac output is inadequate,
(2) abnormal tissue perfusion patterns, so that most of the cardiac output is passing through
blood vessels besides those that supply the local tissues with nutrition.



Mechanism of circulation control

The function of the circulation is to service the needs of the body tissues:
 Transport nutrients to the body tissues
 Transport waste products away
 Conduct hormones from one part of the body to another
 And generally to maintain an appropriate environment in all the tissue fluids of the body
for optimal survival and function of the cells.
The rate of blood flow through most tissues is controlled in response to tissue need for
nutrients. The heart and circulation in turn are controlled to provide the necessary cardiac
output and arterial pressure to cause the needed tissue blood flow.
- Arteries: transport blood under high pressure to the tissues (have strong vascular walls)
- Arterioles: last small branches of the arterial system; act as control conduits through
which blood is released into the capillaries (has a strong muscular wall that can close the
arteriole completely, dilate several fold by relaxing, and have the capability of vastly
altering blood flow in each tissue bed in response to the need of the tissue)
- Capillaries: exchange fluid, nutrients, electrolytes, hormones, and other substances
between the blood and the interstitial fluid (capillary walls are very thin and have capillary
pores that permeable to water and other small molecular substances).
- Venules: collect blood from the capillaries, they gradually merge into progressively
larger veins.
- Veins: function as conduits for transport of blood from the venules back to the heart;
serve as a major reservoir of extra blood (venous walls are thin).

The local control of blood flow in response to tissue needs

Certain organs have special requirements. For instance, blood flow to the skin determines
heat loss from the body and in this way helps to control body temperature. Also, delivery
of adequate quantities of blood plasma to the kidneys allows the kidneys to excrete the
waste products of the body. We shall see that most of these factors exert extreme degrees of
local blood flow control.

Variations in Blood Flow in Different Tissues and Organs

Several hundred milliliters per minute per 100 grams of thyroid or adrenal gland tissue and
a total blood flow of 1350 ml/min in the liver, which is 95 ml/min/100 g of liver tissue.
Extremely large blood flow through the kidneys—1100 ml/min. This extreme amount of
flow is required for the kidneys to perform their function of cleansing the blood of waste
products. Conversely, there is low blood flow to all the inactive muscles of the body, only a
total of 750 ml/min.

Importance of Blood Flow Control by the Local Tissues

The blood flow to each tissue is regulated at the minimal level that will supply the tissue’s
requirements. By controlling local blood flow in such an exact way, the tissues almost
never suffer from oxygen nutritional deficiency, and yet the workload on the heart is kept
at a minimum.

Mechanism of blood flow control

Local blood flow control can be divided into two phases:
(1)Acute Control: rapid changes in local vasodilation or vasoconstriction of the arterioles,
metarterioles, and precapillary sphincters, occurring within seconds to minutes
(2)Long-term Control: means slow, over a period of days, weeks, or even months.

An increase in metabolism up to eight times normal increases the blood flow acutely about

Acute Local Blood Flow Regulation When Oxygen Availability Changes

Whenever oxygen supply to the tissues decreases:
(1) at high altitude at the top of a high mountain,
(2) in pneumonia,
(3) in carbon monoxide poisoning
(4) in cyanide poisoning,

Arterial oxygen saturation decreases to about 25 per cent of normal, the blood flow
through an isolated leg increases about threefold.

Total cyanide poisoning of oxygen usage by a local tissue area can cause local blood flow
to increase as much as sevenfold, thus demonstrating the extreme effect of oxygen
deficiency to increase blood flow.

There are two basic theories for the regulation of local blood flow when either the rate of
tissue metabolism changes or the availability of oxygen changes. They are:

1. Vasodilator Theory for Acute Local Blood Flow Regulation

The greater the rate of metabolism or the less the availability of oxygen or some other
nutrients to a tissue, the greater the rate of formation of vasodilator substances in the tissue
cells. Vasodilator substances: adenosine, carbon dioxide, adenosine phosphate compounds,
histamine, potassium ions, and hydrogen. Vasodilator substance is released from the tissue
mainly in response to oxygen deficiency.
Adenosine is the most important for controlling local blood flow. Minute quantities of
adenosine are released from heart muscle cells when coronary blood flow becomes too
Whenever the heart becomes more active than normal and the heart’s metabolism increases
an extra amount, causes increased utilization of oxygen, followed by (1) decreased oxygen
concentration in the heart muscle cells with (2) consequent degradation of adenosine
triphosphate (ATP), which (3) increases the release of adenosine.

2. Oxygen Lack Theory for Local Blood Flow Control.

Oxygen lack theory or nutrient lack theory (because other nutrients besides oxygen are
involved). In the absence of adequate oxygen, the blood vessels simply would relax and
dilate. Increased utilization of oxygen in the tissues as a result of increased metabolism
theoretically could decrease the availability of oxygen to the smooth muscle fibers in the
local blood vessels, cause local vasodilatation.
Mechanism: This figure shows a tissue unit, consisting of a metarteriole with a single
sidearm capillary and its surrounding tissue. At the origin of the capillary is a precapillary
sphincter, and around the metarteriole are several other smooth muscle fibers. The
precapillary sphincters are normally either completely open or completely closed. The
number of precapillary sphincters that are open at any given time is roughly proportional to
the requirements of the tissue for nutrition, with the duration of the open phases being
proportional to the metabolic needs of the tissues for oxygen. The cyclical opening and
closing is called vasomotion.

Oxygen concentration in the local tissue could regulate blood flow through the area:
Because smooth muscle requires oxygen to remain contracted, one might assume that the
strength of contraction of the sphincters would increase with an increase in oxygen
concentration. Consequently, when the oxygen concentration in the tissue rises above a
certain level, the precapillary and metarteriole sphincters presumably would close until the
tissue cells consume the excess oxygen. But when the excess oxygen is gone and the
oxygen concentration falls low enough, the sphincters would open once more to begin the
cycle again.

Other Nutrients Besides Oxygen in Control of Local Blood Flow: Glocose, amino
acids, fatty acids, vitamin B deficiency (thiamine, niacin, riboflavin). Vitamins are needed
for oxygen induced phosphorylation required to produce ATP in tissue cells.

Mechanism of humoral regulation of the circulation and nervous regulation of the

Humoral control of the circulation means control by substances secreted or absorbed into
the body fluids, such as hormones and ions. These substances are:
- Formed by special glands and transported in the blood throughout the entire body.
- Formed in local tissue areas and cause only local circulatory effects.
Among the most important of the humoral factors:
- Vasoconstrictor Agents: norepinephrine, epinephrine,
- Vasodilator Agents:

A.Vasoconstrictor Agents
A.1 Norepinephrine and Epinephrine
- Main function:
o Norepinephrine: powerful vasoconstrictor hormone
o Epinephrine: less powerful, in some tissues causes mild vasodilation.
- Mechanism:
o The sympathetic nerve endings release norepinephrine (endings of the vasoconstrictor
o The sympathetic nerves cause adrenal medullae to secrete norepinephrine and
o Acts directly on the alpha adrenergic receptors of the vascular smooth muscle to cause
o Has a “beta” adrenergic receptor stimulatory effect, which dilates rather than constricts
certain vessels
- Providing a dual system of control:
o Direct nerve stimulation
o Indirect effects of norepinephrine and/or epinephrine in the circulating blood.

A.2 Angiotensin II
- Function:
o Powerful small arterioles vasoconstrictor
o Increase the total peripheral resistance
o Increase the arterial pressure.

A.3 Vasopressin/Antidiuretic Hormone/ADH

- Function:
o More powerful vasoconstrictor
o Increase arterial pressur
o Increase water reabsorption from the renal tubules
A.4 Endothelin
- Function:
o A powerful vasoconstrictor in damaged blood vessels.
o Only nanogram quantities to cause powerful vasoconstriction.
- Production:
o Endothelial cells of all or most blood vessels.
- Stimulus:
o Endothelium damage, such as crushing the tissues or injecting a traumatizing chemical
into the blood vessel.

B.Vasodilator Agents:
B.1 Bradykinin
- Structure:
o Kinins are small polypeptides that are split away by proteolytic enzymes from alpha2-
globulins in the plasma or tissue fluids.
- Function:
o Powerful arteriolar vasodilatation
o Increased capillary permeability
- Stimulation:
o Tissue inflammation
- Production:
o Blood and tissue fluids of some organs.
- Mechanism:
o A proteolytic enzyme of particular importance for this purpose is kallikrein, which is
present in the blood and tissue fluids in an inactive form.
o As kallikrein becomes activated, it acts immediately on alpha2-globulin to release a
kinin called kallidin that then is converted by tissue enzymes into bradykinin.
o Once formed, bradykinin persists for only a few minutes because it is inactivated by the
enzyme carboxypeptidase or by converting enzyme, the same enzyme that also plays an
essential role in activating angiotensin.
o The activated kallikrein enzyme is destroyed by a kallikrein inhibitor.

B.2. Histamine
- Stimulation:
o Damaged or inflamed tissue
o Allergen
- Function:
o Powerful arterioles vasodilator
o Increase capillary permeability
- Production:
- Every tissue of the body
- Derived from:
 Mast cells in the damaged tissues
 Basophils in the blood.

Vascular Control by Ions and Other Chemical Factors

Many different ions and other chemical factors can either dilate or constrict local blood
vessels. Most of them have little function in overall regulation of the circulation, but some
specific effects are:
1. An increase in calcium ion concentration causes vasoconstriction.
2. An increase in potassium ion concentration causes vasodilation.
3. An increase in magnesium ion concentration causes powerful vasodilation.
4. An increase in hydrogen ion concentration (decrease in pH) causes dilation of the
5. Slight decrease in hydrogen ion concentration causes arteriolar constriction.
6. Acetate and citrate causes mild degrees of vasodilation.
7. An increase in carbon dioxide concentration causes moderate vasodilation in most
tissues, but marked vasodilation in the brain.

The role of the nervous system for rapid control of arterial pressure, special feature of
nervous control of arterial pressure
Nervous control of the circulation has more global functions, such as:
- Redistributing blood flow to different areas of the body
- Increasing or decreasing pumping activity by the heart
- Providing very rapid control of systemic arterial pressure.
The nervous system controls the circulation almost entirely through the autonomic nervous
Autonomic Nervous System
Sympathetic Nervous System.
- Sympathetic nervous system is the most important part of the autonomic nervous system
for regulating the circulation.

- Sympathetic stimulation markedly increases the activity of the heart, both increasing the
heart rate and enhancing its strength and volume of pumping.
- Sympathetic vasoconstrictor effect is especially powerful in the kidneys, intestines,
spleen, and skin but much less potent in skeletal muscle and the brain.
Parasympathetic Control of Heart Function
- Plays only a minor role in regulation of the circulation (vagus nerves)
- Function: decrease in heart rate and a slight decrease in heart muscle contractility.

Vasomotor Center in the Brain and Its Control of the Vasoconstrictor System
- Vasomotor Center: Located bilaterally mainly in the reticular substance of the medulla
and of the lower third of the pons.
- This center transmits parasympathetic impulses through the vagus nerves to the heart
and transmits sympathetic impulses through the spinal cord and peripheral sympathetic
nerves to virtually all arteries, arterioles, and veins of the body.
- Vasomotor center also controls heart activity; can either increase or decrease heart
- Hypothalamus plays a special role in controlling the vasoconstrictor system.
Role of the Nervous System in Rapid Control of Arterial Pressure
Three major changes occur simultaneously, each of which helps to increase arterial
1. Almost all arterioles of the systemic circulation are constricted.
2. The veins especially (but the other large vessels of the circulation as well) are strongly
3. Finally, the heart itself is directly stimulated by the autonomic nervous system, further
enhancing cardiac pumping.

Nervous control of arterial pressure is by far the most rapid of all our mechanisms for
pressure control.

In most heavy exercise/alarm reaction, the arterial pressure rises about 30 to 40 per cent,
which increases blood flow almost an additional twofold. Mechanism: At the same time
that the motor areas of the brain become activated to cause exercise, most of the reticular
activating system of the brain stem is also activated, which includes greatly increased
stimulation of the vasoconstrictor and cardio acceleratory areas of the vasomotor center.
These increase the arterial pressure instantaneously to keep pace with the increase in
muscle activity.

Reflex Mechanisms for Maintaining Normal Arterial Pressure: The Baroreceptor

Arterial Pressure Control System: Baroreceptor Reflexes: A rise in arterial pressure
stretches the baroreceptors and causes them to transmit signals into the central nervous

Physiologic Anatomy of the Baroreceptors and Their Innervation

(1) the wall of each internal carotid artery slightly above the carotid bifurcation (carotid
(2) the wall of the aortic arch.

Response of the Baroreceptors to Pressure:

- Carotid baroreceptors: respond progressively at about 50/60 to 180 mm Hg.
- Aortic baroreceptors:respond at pressure levels about 30 mm Hg higher.
- In the normal operating range of arterial pressure, around 100 mm Hg, even a slight
change in pressure causes a strong change in the baroreflex signal to readjust arterial
pressure back toward normal. Baroreceptor feedback mechanism functions most
effectively in the pressure range where it is most needed.

Circulatory Reflex Initiated by the Baroreceptors

- Baroreceptor signals have entered the tractus solitaries of the medulla
- Secondary signals inhibit the vasoconstrictor center of the medulla and excite the vagal
parasympathetic center.
- The ffects are :
 vasodilation of the veins and arterioles throughout the peripheral circulatory system and
 decreased heart rate and strength of heart contraction.
- The baroreceptors become inactive and lose their inhibitory effect on the vasomotor
- The ability of the baroreceptors to maintain relatively constant arterial pressure in the
upper body is important when a person stands up after having been lying down.
- The baroreceptor system opposes either increases or decreases in arterial pressure are
called a pressure buffer system.
- Although the arterial baroreceptors provide powerful moment-to-moment control of
arterial pressure, their importance in long-term blood pressure regulation has been
controversial; they tend to reset in 1 to 2 days to the pressure level to which they are
- In prolonged increases of arterial pressure, the baroreceptor reflexes may mediate
decreases in renal sympathetic nerve activity that promote increased excretion of sodium
and water by the kidneys; causes a gradual decrease in blood volume, which helps to
restore arterial pressure toward normal.

Control of Arterial Pressure by the Carotid and Aortic Chemoreceptors (Effect of

Oxygen Lack on Arterial Pressure)
- The chemoreceptors are chemosensitive cells sensitive to oxygen lack, carbon dioxide
excess, and hydrogen ion excess.
- Located in several small chemoreceptor organs about 2 millimeters in size.
- Mechanism: Whenever the arterial pressure falls below a critical level, the
chemoreceptors become stimulated because diminished blood flow causes decreased
oxygen as well as excess buildup of carbon dioxide and hydrogen ions that are not
removed by the slowly flowing blood. The signals transmitted from the chemoreceptors
excite the vasomotor center, and this elevates the arterial pressure back toward normal.
- Works when the arterial pressure falls below 80 mm Hg.

Atrial and Pulmonary Artery Reflexes That Help Regulate Arterial Pressure and
Other Circulatory Factors
- Artial and pulmonary low-pressure receptors play an important role, especially in
minimizing arterial pressure changes in response to changes in blood volume.

Atrial Reflexes That Activate the Kidneys (The “Volume Reflex).

- Stretch of the atria also causes significant reflex dilation of the afferent arterioles in the
- Decrease secretion of antidiuretic hormone.
- The decreased afferent arteriolar resistance in the kidneys causes the glomerular
capillary pressure to rise, with resultant increase in filtration of fluid into the kidney
- The decrease of antidiuretic hormone diminishes the reabsorption of water from the
tubules. Combination of these two effects— increase in glomerular filtration and decrease
in reabsorption of the fluid—increases fluid loss by the kidneys and reduces an increased
blood volume back toward normal.

Atrial Reflex Control of Heart Rate (the Bainbridge Reflex)

- An increase in atrial pressure also causes an increase in heart rate, sometimes increasing
the heart rate as much as 75 per cent.A small part of this increase is caused by a direct
effect of the increased atrial volume to stretch the sinus node: it was pointed out in Chapter
10 that such direct stretch can increase the heart rate as much as 15 per cent. An additional
40 to 60 per cent increase in rate is caused by a nervous reflex called the Bainbridge
reflex.The stretch receptors of the atria that elicit the Bainbridge reflex transmit their
afferent signals through the vagus nerves to the medulla of the brain. Then efferent signals
are transmitted back through vagal and sympathetic nerves to increase heart rate and
strength of heart contraction. Thus, this reflex helps prevent damming of blood in the
veins, atria, and pulmonary circulation.

Central Nervous System Ischemic Response: Control of Arterial Pressure by the

Brain’s Vasomotor Center in Response to Diminished Brain Blood Flow
- Failure of the slowly flowing blood to carry carbon dioxide away from the brain stem
vasomotor center
- At low levels of blood flow to the vasomotor center, the local concentration of carbon
dioxide increases greatly and has an extremely potent effect in stimulating the sympathetic
vasomotor nervous control areas in the brain’s medulla.
- The degree of sympathetic vasoconstriction caused by intense cerebral ischemia is often
so great that some of the peripheral vessels become totally or almost totally occluded. CNS
ischemic response is one of the most powerful of all the activators of the sympathetic
vasoconstrictor system.

Cardiac Output, Venous Return, and Their Regulation

Cardiac output is the quantity of blood pumped into the aorta each minute by the heart.
This is also the quantity of blood that flows through the circulation. Cardiac output is
perhaps the most important factor that we have to consider in relation to the circulation.
Venous return is the quantity of blood flowing from the veins into the right atrium each
minute. The venous return and the cardiac output must equal each other except for a few
heartbeats at a time when blood is temporarily stored in or removed from
the heart and lungs.
Normal Values for Cardiac Output at Rest and During Activity
Cardiac output varies widely with the level of activity of the body.
The following factors, among others, directly affect cardiac output:
(1) the basic level of body metabolism,
(2) whether the person is exercising,
(3) the person’s age, and
(4) size of the body.
For young, healthy men, resting cardiac output averages about 5.6 L/min. For women, this
value is about 4.9 L/min. When one considers the factor of age as well—because with
increasing age, body activity diminishes—the average cardiac output for the resting adult,
in round numbers, is often stated to be almost exactly 5 L/min.

Control of Cardiac Output by Venous Return—Role of the Frank-Starling

Mechanism of the Heart

When one states that cardiac output is controlled by venous return, this means that it is not
the heart itself that is the primary controller of cardiac output
Instead, it is the various factors of the peripheral circulation that affect flow of blood into
the heart from the veins, called venous return, that are the primary controllers.
The main reason peripheral factors are usually more important than the heart itself in
controlling cardiac output is that the heart has a built-in mechanism that normally allows it
to pump automatically whatever amount of blood that flows into the right atrium from the
veins. Basically, this law states that when increased quantities of blood flow into the heart,
the increased blood stretches the walls of the heart chambers. As a result of the stretch, the
cardiac muscle contracts with increased force, and this empties the extra blood that has
entered from the systemic circulation. Therefore, the blood that flows into the heart is
automatically pumped without delay into the aorta and flows again through the circulation.
Another important factor, is that stretching the heart causes the heart to pump faster—at an
increased heart rate. That is, stretch of the sinus node in the wall of the right atrium has a
direct effect on the rhythmicity of the node itself to increase heart rate as much as 10 to 15
per cent. In addition, the stretched right atrium initiates a nervous reflex called the
Bainbridge reflex, passing first to the vaso- motor center of the brain and then back to the
heart by way of the sympathetic nerves and vagi, also to increase the heart rate.

Under most normal unstressful conditions, the cardiac output is controlled almost entirely
by peripheral factors that determine venous return. However, we shall see later in the
chapter that if the returning blood does become more than the heart can pump, then the
heart becomes the limiting factor that determines cardiac output.

Pathologically High and Pathologically Low Cardiac Outputs

In healthy human beings, the cardiac outputs are surprisingly constant from one person to
another. However, multiple clinical abnormalities can cause either high or low cardiac

High Cardiac Output Caused by Reduced Total Peripheral Resistance

The conditions that can decrease the peripheral resistance and at the same time increase the
cardiac output to above normal.
1. Beriberi. This disease is caused by insufficient quantity of the vitamin thiamine (vitamin
B1) in the diet. Lack of this vitamin causes diminished ability of the tissues to use some
cellular nutrients, and the local tissue blood flow mechanisms in turn cause marked
compensatory peripheral vasodilation. Sometimes the total peripheral resistance decreases
to as little as one-half normal. Consequently, the long-term levels of venous return and
cardiac output also often increase to twice normal.

2. Arteriovenous fistula (shunt). Earlier, we pointed out that whenever a fistula (also called
an AV shunt) occurs between a major artery and a major vein, tremendous amounts of
blood flow directly from the artery into the vein. This, too, greatly decreases the total
peripheral resistance and, likewise, increases the venous return and cardiac output.
3. Hyperthyroidism. In hyperthyroidism, the metabolism of most tissues of the body
becomes greatly increased. Oxygen usage increases, and vasodilator products are released
from the tissues. Therefore, the total peripheral resistance decreases markedly because of
the local tissue blood
flow control reactions throughout the body; consequently, the venous return and cardiac
output often increase to 40 to 80 per cent above normal.
4. Anemia. In anemia, two peripheral effects greatly decrease the total peripheral
resistance. One of these is reduced viscosity of the blood, resulting from the decreased
concentration of red blood cells. The other is diminished delivery of oxygen to the tissues,
which causes local vasodilation. As a consequence, the cardiac output increases greatly.
Low Cardiac Output

Figure 20–6 shows at the far right several conditions that cause abnormally low cardiac
output. These conditions fall into two categories:
(1) those abnormalities that cause the pumping effectiveness of the heart to fall too low and
(2) those that cause venous return to fall too low.

Decreased Cardiac Output Caused by Cardiac Factors.

Whenever the heart becomes severely damaged, regardless of the cause, its limited level of
pumping may fall below that needed for adequate blood flow to the tissues. Some
examples of this include :
(1) severe coronary blood vessel blockage and consequent myocardial infarction,
(2) severe valvular heart disease,
(3) myocarditis,
(4) cardiac tamponade, and
(5) cardiac metabolic derangements.

The effects of several of these are shown on the right in Figure 20–6, demonstrating the
low cardiac outputs that result.
When the cardiac output falls so low that the tissues throughout the body begin to suffer
nutritional deficiency, the condition is called cardiac shock.
Decrease in Cardiac Output Caused by Non-cardiac Peripheral Factors
Decreased Venous Return. Anything that interferes with venous return also can lead to
decreased cardiac output. Some of these factors are the following:
1. Decreased blood volume. By far, the most
common non-cardiac peripheral factor that leads to decreased cardiac output is decreased
blood volume, resulting most often from hemorrhage. It is clear why this condition
decreases the cardiac output: Loss of blood decreases the filling of the vascular system to
such a low level that there is not enough blood in the peripheral vessels to create peripheral
vascular pressures high enough to push the blood back to the heart.
2. Acute venous dilation. On some occasions, the peripheral veins become acutely
vasodilated. This results most often when the sympathetic nervous system suddenly
becomes inactive. For instance, fainting often results from sudden loss of sympathetic
nervous system activity, which causes the peripheral capacitative vessels, especially the
veins, to dilate markedly. This decreases the filling pressure of the vascular system because
the blood volume can no longer create adequate pressure in the now flaccid peripheral
blood vessels. As a result, the blood “pools” in the vessels and does not return to the heart.
3. Obstruction of the large veins. On rare occasions, the large veins leading into the heart
become obstructed, so that the blood in the peripheral vessels cannot flow back into the
heart. Consequently, the cardiac output falls markedly.
4. Decreased tissue mass, especially decreased skeletal muscle mass. With normal aging or
with prolonged periods of physical inactivity, there is usually a reduction in the size of the
skeletal muscles. This, in turn, decreases the total oxygen consumption and blood flow
needs of the muscles, resulting in decreases in skeletal muscle blood flow and cardiac
Regardless of the cause of low cardiac output, whether it be a peripheral factor or a cardiac
factor, if ever the cardiac output falls below that level required for adequate nutrition of the
tissues, the person is said to suffer circulatory shock. This condition can be lethal within a
few minutes to a few hours.

A More Quantitative Analysis of Cardiac Output Regulation

To perform the more quantitative analysis, it is necessary to distinguish separately the two
primary factors concerned with cardiac output regulation:
(1) the pumping ability of the heart, as represented by cardiac output curves, and
(2) the peripheral factors that affect flow of blood from the veins into the heart, as
represented by venous return curves. Then one can put these curves together in a
quantitative way to show how they interact with each other to determine cardiac output,
venous return, and right atrial pressure at the same time.

Methods for Measuring Cardiac Output

In animal experiments, one can cannulate the aorta, pulmonary artery, or great veins
entering the heart and measure the cardiac output using any type of flowmeter. An
electromagnetic or ultrasonic flowmeter can also be placed on the aorta or pulmonary
artery to measure cardiac output.
In the human, except in rare instances, cardiac output is measured by indirect methods that
do not require surgery. Two of the methods commonly used are the oxygen Fick method
and the indicator dilution method.


LO: Understand the pathogenesis and histopathologic changes of cardiac hypertrophy,
dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy and
myocarditis in heart failure:
Kumar V, Abbas AK, Fausto N, Aster Jc. Robins and Cotrans Pathologic Basis of Disease
8th Edtion, Saunders Elsevier Philladelpia. P487-585

Myocardial adaptations, including hypertrophy with or without cardiac chamber dilation.

The collective molecular, cellular, and structural changes that occur as a response to injury
or changes in loading conditions are called ventricular remodeling. Often adaptive,
especially in early stages, these changes can culminate in impaired cardiac function. In
many pathologic states, heart failure is preceded by cardiac hypertrophy, the compensatory
response of the myocardium to increased mechanical work.
These adaptive mechanisms may be adequate to maintain normal cardiac output in the face
of heart disease, but their capacity to do so may ultimately be overwhelmed. Moreover,
superimposed pathologic changes, such as myocyte apoptosis, cytoskeletal alterations, and
the deposition of extracellular matrix may cause further structural and functional
disturbances. Most frequently, heart failure results from progressive deterioration of
myocardial contractile function (systolic dysfunction); this may be attributable to ischemic
injury, pressure or volume overload due to valvular disease or hypertension, or dilated
cardiomyopathy. Sometimes, however, failure results from an inability of the heart
chamber to expand and fill sufficiently during diastole (diastolic dysfunction), as can occur
with massive left ventricular hypertrophy, myocardial fibrosis, deposition of amyloid, or
constrictive pericarditis


Drug Groups Commonly Used in Heart Failure.

Aldosterone receptor antagonists
Angiotensin-converting enzyme inhibitors
Angiotensin receptor blockers
Beta blockers
Cardiac glycosides
Beta agonists
Natriuretic peptide

Digitalis (digoxin oral tablet 0,125; 0,25 mg; cap : 0,05;0,1;0,2 mg,elixir 0,05 mg/ml,
parenteral : 0,1;0,25 mg/ml), mechanism of action : Na-K-ATPase inhibition --> reduced
Ca expulsion and increase Ca stored in SR --> cardiac parasympathomimetic (slowed
sinus heart rate, slow atrioventricular conduction) --> increases cardiac contractility.
Warning : Digoxin have narrow theurapeutic index. Captopril : reduce salt and water
retention (by reducing aldosterone secretion) --> reduce preload,reduces sympathetic
activity through diminution of angiotensin's presynaptic effects on norepinephrine release--
> reduce the long-term remodeling of the heart and vessels --> reduce peripheral
resistance,reduce afterload. Furosemid : reduce venous pressure and ventricular preload -->
reduction of salt and water retention --> reduce edema. The reduction of cardiac size -->
improved pump efficiency --> improve oxygenation & improve myocardial function.
Reduction of preload --> reduce the size of the heart, allowing it to work at a more efficient
fiber length. Adverse effect of digoxin : cardiac arrhytmias, nausea, vomitting, diarrhea;
captopril : cough, furosemid: hypokalemic metabolic
alkalosis,ototoxicity,hyperuricemia,hypomagnesia; Isosorbid dinitrat : orthostatic
hypotension. Morphine : Strong µ-receptor agonists --> Analgesia,relief of anxiety
sedation,slowed gastrointestinal transit. Toxicity:
Respiratory depression, severe
constipation, addiction liability.
Preparation available : Morphine sulfate (generic, others)
Oral: 15, 30 mg tablets; 15, 30 mg capsules; 10, 20, 100 mg/5 mL solution
Oral sustained-release tablets (MS-Contin, others): 15, 30, 60, 100, 200 mg tablets
Oral sustained-release capsules (Avinza, Kadian): 20, 30, 50, 60, 90, 100, 120 mg capsules
Parenteral: 0.5, 1, 2, 4, 5, 8, 10, 15, 25, 50 mg/mL for injection
Rectal: 5, 10, 20, 30 mg suppositories.

Dobutamin : Activates adenylylcyclase --> increasing myocardial contractility --> Positive

inotropic. Administration : IV only,duration a few minutes, requires dose titration to
desired effect.
Preparation available
Dobutamine (generic, Dobutrex)
Parenteral: 12.5 mg/mL in 20 mL vials for injection , 12,5 mg/ml for iv. infusion
Toxicity: Arrhythmias. Dopamin : Activates adenylyl cyclase --> Vascular smooth muscle
relaxation.Administration :Requires dose titration to desired effect.
Preparation available : Dopamine (generic, Intropin)
Parenteral: 40, 80, 160 mg/mL for injection; 80, 160, 320 mg/100
mL in 5% D/W for injection. Epinephrine : agonist at both α and β receptors --> positive
inotropic and chronotropic on the heart (predominantly β1 receptors) and the
vasoconstriction in vascular beds (α receptors) --> increase systolic blood pressure -->
redistributing blood flow during cardiopulmonary resuscitation to coronaries and to the
brain. norepinephrine : agonist β1 and β2 receptors, increases peripheral resistance and
both diastolic and
systolic blood pressure --> Compensatory baroreflex activation --> direct positive

Schematic diagram of a cardiac muscle sarcomere, with sites of action of several drugs that
alter contractility. Na+,K+ ATPase, the sodium pump, is the site of action of cardiac
glycosides. NCX is the sodium, calcium exchanger. Ca v-L is the voltage-gated, L-type
calcium channel. SERCA (sarcoplasmic endoplasmic reticulum Ca2+-ATPase) is a calcium
transporter ATPase that pumps calcium into the sarcoplasmic reticulum (SR). CalS is
calcium bound to calsequestrin, a high-capacity Ca 2+-binding protein. RyR (ryanodine
RyR2 receptor) is a calcium-activated calcium channel in the membrane of the SR that is
triggered to release stored calcium. Calcium sensitizers act at the actin-troponin-
tropomyosin complex where activator calcium brings about the contractile interaction of
actin and myosin. Black arrows represent processes that initiate contraction or support
basal tone. Green arrows represent processes that promote relaxation

Digoxin, the only cardiac glycoside used in the USA, is 65–80% absorbed after oral
administration. Absorption of other glycosides varies from zero to nearly 100%. Once
present in the blood, all cardiac glycosides are widely distributed to tissues, including the
central nervous system.
Digoxin is not extensively metabolized in humans; almost two thirds is excreted
unchanged by the kidneys. Its renal clearance is proportional to creatinine clearance and
the half-life is 36–40 hours in patients with normal renal function. Equations and
nomograms are available for adjusting digoxin dosage in patients with renal impairment.
Digoxin has multiple direct and indirect cardiovascular effects, with both therapeutic and
toxic consequences. In addition, it has undesirable effects on the central nervous system
and gut.
At the molecular level, all therapeutically useful cardiac glycosides inhibit Na +,K +
ATPase, the membrane-bound transporter often called the sodium pump (Figure 13–1).
Inhibition of this transporter over most of the dose range has been extensively documented
in all tissues studied. It is probable that this inhibitory action is largely responsible for the
therapeutic effect (positive inotropy) as well as a major portion of the toxicity of digitalis.
Other molecular-level effects of digitalis have been studied in the heart and are discussed
below. The fact that a receptor for cardiac glycosides exists on the sodium pump has
prompted some investigators to propose that an endogenous digitalis-like steroid, possibly
ouabain, must exist.
Cardiac Effects
Mechanical Effects
Cardiac glycosides increase contraction of the cardiac sarcomere by increasing the free
calcium concentration in the vicinity of the contractile proteins during systole. The increase
in calcium concentration is the result of a two-step process: first, an increase of
intracellular sodium concentration because of Na+,K+ ATPase inhibition; and second, a
relative reduction of calcium expulsion from the cell by the sodium-calcium exchanger
(NCX in Figure 13–1) caused by the increase in intracellular sodium. The increased
cytoplasmic calcium is sequestered by SERCA in the SR for later release. Other
mechanisms have been proposed but are not well supported.
The net result of the action of therapeutic concentrations of a cardiac glycoside is a
distinctive increase in cardiac contractility (Figure 13–5, bottom trace). In isolated
myocardial preparations, the rate of development of tension and of relaxation are both
increased, with little or no change in time to peak tension. This effect occurs in both
normal and failing myocardium, but in the intact patient the responses are modified by
cardiovascular reflexes and the pathophysiology of heart failure.
Electrical Effects
The effects of digitalis on the electrical properties of the heart are a mixture of direct and
autonomic actions. Direct actions on the membranes of cardiac cells follow a well-defined
progression: an early, brief prolongation of the action potential, followed by shortening
(especially the plateau phase). The decrease in action potential duration is probably the
result of increased potassium conductance that is caused by increased intracellular calcium
(see Chapter 14). All these effects can be observed at therapeutic concentrations in the
absence of overt toxicity.

At higher concentrations, resting membrane potential is reduced (made less negative) as a

result of inhibition of the sodium pump and reduced intracellular potassium. As toxicity
progresses, oscillatory depolarizing afterpotentials appear following normally evoked
action potentials. The afterpotentials (also known as delayed after depolarizations,
DADs) are associated with overloading of the intracellular calcium stores and oscillations
in the free intracellular calcium ion concentration. When afterpotentials reach threshold,
they elicit action potentials (premature depolarizations, ectopic “beats”) that are coupled
to the preceding normal action potentials. If afterpotentials in the Purkinje conducting
system regularly reach threshold in this way, bigeminy will be recorded on the
electrocardiogram. With further intoxication, each afterpotential-evoked action potential
will itself elicit a suprathreshold afterpotential, and a self-sustaining tachycardia is
established. If allowed to progress, such a tachycardia may deteriorate into fibrillation; in
the case of ventricular fibrillation, the arrhythmia will be rapidly fatal unless corrected.
Autonomic actions of cardiac glycosides on the heart involve both the parasympathetic and
the sympathetic systems. In the lower portion of the dose range, cardioselective
parasympathomimetic effects predominate. In fact, these atropine-blockable effects
account for a significant portion of the early electrical effects of digitalis (Table 13–2).
This action involves sensitization of the baroreceptors, central vagal stimulation, and
facilitation of muscarinic transmission at the cardiac muscle cell. Because cholinergic
innervation is much richer in the atria, these actions affect atrial and atrioventricular nodal
function more than Purkinje or ventricular function. Some of the cholinomimetic effects
are useful in the treatment of certain arrhythmias. At toxic levels, sympathetic outflow is
increased by digitalis. This effect is not essential for typical digitalis toxicity but sensitizes
the myocardium and exaggerates all the toxic effects of the drug.
The most common cardiac manifestations of digitalis toxicity include atrioventricular
junctional rhythm, premature ventricular depolarizations, bigeminal rhythm, and second-
degree atrioventricular blockade. However, it is claimed that digitalis can cause virtually
any arrhythmia.

Drugs Without Positive Inotropic Effects Used in Heart Failure

Paradoxically, these agents—not positive inotropic drugs—are the first-line therapies for
chronic heart failure. The drugs most commonly used are diuretics, ACE inhibitors,
angiotensin receptor antagonists, aldosterone antagonists, and β-blockers (Table 13–1). In
acute failure, diuretics and vasodilators play important roles.

Diuretics are the mainstay of heart failure management. They have no direct effect on
cardiac contractility; their major mechanism of action in heart failure is to reduce venous
pressure and ventricular preload. This results in reduction of salt and water retention and
edema and its symptoms. The reduction of cardiac size, which leads to improved pump
efficiency, is of major importance in systolic failure. Spironolactone and eplerenone, the
aldosterone antagonist diuretics, have the additional benefit of decreasing morbidity and
mortality in patients with severe heart failure who are also receiving ACE inhibitors and
other standard therapy. One possible mechanism for this benefit lies in accumulating
evidence that aldosterone may also cause myocardial and vascular fibrosis and
baroreceptor dysfunction in addition to its renal effects.
Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, &
Related Agents
ACE inhibitors such as captopril are reduce peripheral resistance and thereby reduce
afterload; they also reduce salt and water retention (by reducing aldosterone secretion) and
in that way reduce preload. The reduction in tissue angiotensin levels also reduces
sympathetic activity through diminution of angiotensin’s presynaptic effects on
norepinephrine release. Finally, these drugs reduce the long-term remodeling of the heart
and vessels, an effect that may be responsible for the observed reduction in mortality and
Angiotensin AT1 receptor-blockers such as losartan appear to have similar but more
limited beneficial effects. Angiotensin receptor blockers should be considered in patients
intolerant of ACE inhibitors because of incessant cough. In some trials, candesartan was
beneficial when added to an ACE inhibitor.
Aliskiren, a renin inhibitor recently approved for hypertension, is in clinical trials for heart
failure. Preliminary results suggest an efficacy similar to that of ACE inhibitors.

1. Braunwald’s Heart Disease : A Textbook of Cardiovascular Medicine. 7th ed. 2005
2. Branch JR TW, Alexander RW, Schlant RC, Willis Hurst J. Cardiology in Primary Care.
McGraw-Hill Int, New York, 2000 : 791 - 805.
3. Robin’s and Cotran, Basic Disease of Pathology
4. Guyton
5. Basic of Histology
6. Moore, anatomy

Dept. Cardiology

Heart Failure

Heart failure can be defined as an abnormality of cardiac structure or function leading to
failure of the heart to deliver oxygen at a rate commensurate with the requirements of the
metabolizing tissues, despite normal filling pressures (or only at the expense of increased
filling pressures).

For the purposes of these guidelines, HF is defined, clinically, as a syndrome in which

patients have typical symptoms (e.g.breathlessness, ankle swelling, and fatigue) and signs
(e.g. elevated jugular venous pressure, pulmonary crackles, and displaced apex beat)
resulting from an abnormality of cardiac structure or function.


Terminology related to left ventricular ejection fraction

The main terminology used to describe HF is historical and is based on measurement of LV
ejection fraction (EF). Mathematically, EF is the stroke volume (which is the end-diastolic
volume minus the end-systolic volume) divided by the end-diastolic volume. The major
trials in patients with HF and a reduced EF (HF-REF), or ‘systolic HF’, mainly enrolled
patients with an EF≤35%. HF with ‘preserved’ EF (HF-PEF), or ‘diastolic HF’ was created
to describe these patients patients with HF and an EF more than 50%% and no other causal
cardiac abnormality (such as valvular or pericardial disease). Patients with an EF in the
range 35–50% therefore represent a ‘grey area’ and most probably have primarily mild
systolic dysfunction.

Terminology related to the time-course of heart failure

A patient who has never exhibited the typical signs or symptoms of HF is described as
having asymptomatic LV systolic dysfunction (or whatever the underlying cardiac
abnormality is). Patients who have had HF for some time are often said to have ‘chronic
HF’. A treated patient with symptoms and signs, which have remained generally
unchanged for at least a month, is said to be ‘stable’. If chronic stable HF deteriorates, the
patient may be described as ‘decompensated’ and this may happen suddenly, i.e. ‘acutely’,
usually leading to hospital admission, an event of considerable prognostic importance.
‘Congestive HF’ is a term that is sometimes still used, particularly in the USA, and may
describe acute or chronic HF with evidence of congestion (i.e. sodium and water retention).
Congestion, though not other symptoms of HF (e.g. fatigue), may resolve with diuretic
treatment. Many or all of these terms may be accurately applied to the same patient at
different times, depending upon their stage of illness.

Terminology related to the symptomatic severity of heart failure

The NYHA functional classification (table below) has been used to select patients in
almost all randomized treatment trials in HF and, therefore, to describe which patients
benefit from effective therapies. Patients in NYHA class I have no symptoms attributable
to heart disease; those in NYHA classes II, III or IV are sometimes said to have mild,
moderate or severe symptoms, respectively.

Class I (mild) No limitation of physical activity
Ordinary physical activity does not cause undue fatigue,
palpitation, or dyspnea (shortness of breath)
Class II (mild) Slight limitation of physical activity
Comfortable at rest, but ordinary physical activity results in
fatigue, palpitation, or dyspnea
Class III Marked limitation of physical activity
(moderate) Comfortable at rest, but less than ordinary activity causes
fatigue, palpitation, or dyspnea
Class IV Unable to carry out any physical activity without discomfort
(severe) Symptoms of cardiac insufficiency at rest
If any physical activity is undertaken, discomfort is


Patients with heart failure may complain of a vast array of symptoms, the most common of
which are listed in table below.

Symptoms Associated With Heart Failure

Shortness of breath at rest or during exercise
Diminished exercise capacity
Paroxysmal nocturnal dyspnea
Weight gain or weight loss
Edema (of the extremities, scrotum, or
Increasing abdominal girth or bloating
Abdominal pain (particularly confined to the
right upper quadrant)
Loss of appetite or early satiety
History of Cheyne-Stokes respirations during
sleep (often reported by the family rather than by
the patient)
Somnolence or diminished mental acuity

Dyspnea (the subjective complaint of discomfort while breathing), shortness of breath, and
fatigue are common complaints of heart failure patients. Patients with worsening heart
failure frequently experience exertional dyspnea, and this symptom often triggers a visit to
the clinic or emergency department. Patients may sleep with their heads elevated to relieve
symptoms of pulmonary congestion, but they may also sleep upright because of an
enlarged abdominal pannus, esophageal reflux, or orthopedic problems. The authors have
found the complaint of paroxysmal nocturnal dyspnea to be a highly reliable indicator of
the presence of heart failure. Classically, the patient experiences nocturnal awakenings
usually occurring at a fixed time after retiring (often in the range of 1 to 2 hours)
precipitated by the subjective feeling of air hunger, smothering, or drowning that causes
the patient to sit upright (sometimes seeking fresh air from an open window) for a period
of 15 to 30 minutes before resolution.

Other Historical Information

Information about a patient’s past and current medical problems and the patient’s family
and social history provides the background on which symptoms are interpreted and a
management plan is designed. The likelihood of a given constellation of symptoms being
due to heart failure will increase when there is a history of heart failure or risk factors
known to be associated with cardiac disease. The presence of hypertension, coronary artery
disease, or diabetes is particularly helpful because these conditions account for
approximately 90% of the population’s attributable risk for heart failure in the United

Historical Information That Is Helpful in

Determining if Symptoms Are Due to Heart
A past history of heart failure
Cardiac disease (e.g., coronary artery, valvular,
or congenital disease; previous myocardial
Risk factors for heart failure (e.g., diabetes,
hypertension, obesity)
Systemic illnesses that can involve the heart
(e.g., amyloidosis, sarcoidosis, inherited
neuromuscular diseases)
Recent viral illness or history of human
immunodeficiency virus infection or Chagas
Family history of heart failure or sudden cardiac
Environmental or medical exposure to
cardiotoxic substances
Substance abuse
Noncardiac illnesses that could affect the heart
indirectly (including high-output states such as
anemia, hyperthyroidism, arteriovenous fistulas)

Physical Examination
The physical findings listed in table below, complement information from the medical
history in defining the presence and severity of heart failure. The typical (and atypical)
signs of heart failure have been extensively described.

 Tachycardia
 Extra beats or irregular rhythm
 Narrow pulse pressure or thready pulse*
 Pulsus alternans*
 Tachypnea
 Cool or mottled extremities*
 Elevated jugular venous pressure
 Dullness and diminished breath sounds at one or both lung bases
 Rales, rhonchi, or wheezes
 Apical impulse displaced leftward or inferiorly
 Sustained apical impulse
 Parasternal lift
 S3 or S4 (either palpable or audible)
 Tricuspid or mitral regurgitant murmur
 Hepatomegaly (often accompanied by right upper quadrant discomfort)
 Ascites
 Presacral edema
 Anasarca*
 Pedal edema
 Chronic venous stasis changes

Routine Tests
An algorithm for the diagnosis of heart failure or left ventricular dysfunction is presented
in Figure below. The diagnosis of heart failure alone is not sufficient; it is important to
establish the cause of heart failure, insofar as some forms of heart failure may be
correctable or may require special treatment that goes beyond the conventional treatment

Flow chart for the evaluation of patients with heart failure. CXR = chest radiography;
ECG = electrocardiography; echo = echocardiography; HF = heart failure; Hx = history;
NP = natriuretic peptides.

Chest X-Ray

Despite dependence on echocardiography to determine cardiac chamber size and function

and on biomarkers to distinguish heart failure from other causes of dyspnea, chest
radiography remains a useful component of the assessment, particularly when the clinical
presentation is ambiguous. A “butterfly” pattern of alveolar opacities that fan out
bilaterally from engorged hilar pulmonary arteries to the periphery of the lungs is the
classic pattern of congestion seen in decompensated heart failure (see Fig. below). Many
patients, however, present with a more subtle picture in which increased interstitial mark-
ings including Kerley B lines (thin horizontal linear opacities extending to the pleural
surface caused by accumulation of fluid in the interstitial space), peribronchial cuffing, and
evidence of prominent upper lobe vasculature (indicating pulmonary venous hypertension)
are the most prominent chest radiographic findings.

Patient with acute pulmonary edema.

Note engorged hila bilaterally, with
typical pattern of pulmonary edema on
the right. Also note intra-aortic
counterpulsation balloon with
radiopaque tip at the top of the
descending aorta (small arrow) and the
balloon expanded in the aorta below it
(large arrow).

The electrocardiogram (ECG) is a standard part of the initial evaluation of a patient with
suspected heart failure and also when previously diagnosed patients experience an episode
of decompensation. Sinus tachycardia due to sympathetic nervous system activation is seen
with advanced heart failure or during episodes of decompensation. The presence of left
ventricular hypertrophy can provide clues about the cause (e.g., hypertension or valvular
disease) as picted in figure below. If right ventricular hypertrophy is present, conditions
that cause primary or secondary pulmonary hypertension should be considered. The
presence of Q waves suggests that heart failure may have been caused by a myocardial

Measurement of Blood Chemistry and Hematologic Variables

Blood chemistries and hematologic variables are routinely measured as part of the initial
heart failure evaluation. The results provide information that is essential in considering
management strategies as well as for the detection of comorbidities that could complicate
evaluation and treatment. Repeated determination of electrolyte values, renal function, and
other variables is also required as the clinical course develops over time. Electrolyte levels
in blood are determined intermittently, with the frequency dictated by the clinical situation.
Hyponatremia is common in heart failure patients, particularly during periods of
decompensation. Hypokalemia occurs commonly in heart failure patients who are treated
with diuretics. It can increasing the risk of cardiac arrhythmias. Diabetes is common in
heart failure patients. High plasma glucose levels indicate the presence of this disease as
well as the failure of glycemic control. Because diuretics can cause gout, measurement of
uric acid levels can help in management of the patient.

Measurement of biomarkers has emerged during the past decade as an important means of
distinguishing heart failure from other conditions, particularly when there is ambiguity in
the clinical presentation. The most widely used are the natriuretic peptides, mainly brain
natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP). Release of these
peptides is enhanced by increased hemodynamic stress due to either ventricular
hypertrophy or dilation or by increased wall stress. Natriuretic peptide levels increase
progressively with worsening NYHA functional class. Whereas BNP and NT-proBNP are
elevated in patients with dyspnea due to decompensated heart failure, the levels tend to be
greater in patients with systolic dysfunction than in patients with heart failure and
preserved ejection fraction.

Management of Heart Failure

The goals of treatment in patients with established HF are to relieve symptoms and signs
(e.g. oedema), prevent hospital admission, and improve survival.

*Thrombo-embolism prophylaxis should also be considered in parallel.

†Beta-blocker treatment can cause worsening in acutely decompensated patients with HF-
REF (see section on acute heart failure).
°Rate-limiting CCBs should be avoided in HF-REF.
AV = atrioventricular; CCB = calcium-channel blocker; HF-PEF = heart failure with
preserved ejection fraction; HF-REF = heart failure with reduced ejection fraction.

Acute heart failure

Acute heart failure (AHF) is the term used to describe the rapid onset of, or change in,
symptoms and signs of HF. It is a lifethreatening condition that requires immediate medical
attention and usually leads to urgent admission to hospital. In most cases, AHF arises as a
result of deterioration in patients with a previous diagnosis of HF (either HF-REF or HF-
PEF), and all of the aspects of chronic management described in these guidelines apply
fully to these patients. In patients with pre-existing HF there is often a clear precipitant or
trigger (e.g. an arrhythmia or discontinuation of diuretic therapy in a patient with HF-REF
and volume overload or severe hypertension in patients with HF-PEF).

CPAP = continuous positive airway pressure; ETT = endotracheal tube; i.v. = intravenous;
NIPPV = non-invasive positive pressure ventilation; NIV = non-invasive ventilation; NTG
= nitroglycerine; PaO2 = partial pressure of oxygen; SBP = systolic blood pressure; SpO2
= saturation of peripheral oxygen.

Reference :

1. Braunwald E, Zipes DP, Libby P. Heart Disease, A Textbook of Cardiovascular

Medicine. 9th Ed,. WB Saunders Coy, Philadelphia, 2011: Chapter 26-28, 30. Clinical
Assessment of Heart Failure; Diagnosis and Management of Acute Heart Failure
Syndromes; Management of Heart Failure with Reduced Ejection Fraction; Heart Failure
with Normal Ejection Fraction.
2. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al.
ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012.
European Heart Journal. 2012;33:1787–847.

TUTOR GUIDE CRP for heart failure:

Based on the most recent references at least six heart failure (HF) scoring
methodologies based upon symptoms and signs have been developed to assess the
presence of heart failure. A 2013 update from the American Heart Association (AHA)
estimated that there were 5.1 million people with HF in the United States in 2006.
There are an estimated 23 million people with HF worldwide. Regardless of the
definition used, the prevalence of HF and left ventricular dysfunction increases
steeply with age. As an example, the Framingham Heart Study found a prevalence of
HF in men of 8 per 1000 at age 50 to 59 years, increasing to 66 per 1000 at ages 80 to
89 years; similar values (8 and 79 per 1000) were noted in women. The prevalence in
African-Americans is reported to be 25 percent higher than in whites.

The magnitude of the problem of HF cannot be assessed with precision since reliable,
population-based estimates of its prevalence, incidence, and prognosis are lacking. Part of
the problem is that large differences exist among studies in their definition of the condition
and the methods used to establish its presence. In addition, presymptomatic left ventricular
dysfunction is now used increasingly as an indicator of impending, if not existing, HF.

Alternative Solutions
Heart failure has been singled out as an emerging epidemic, which could be the result of
increased incidence and/or increased survival leading to increased prevalence. Knowledge
of the responsibility of each factor in the genesis of the epidemic is crucial for prevention.
Population-based studies have shown that, over time, the incidence of heart failure
remained overall stable, while survival improved. Therefore, the heart failure epidemic is
chiefly one of hospitalizations. Data on temporal trends in the incidence and prevalence of
heart failure how it may have changed over time are needed while interventions should
focus on reducing the burden of hospitalizations in heart failure.

– Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the
Framingham Study. J Am Coll Cardiol 1993; 22:6A.
– Cowie MR, Mosterd A, Wood DA, et al. The epidemiology of heart failure. Eur Heart J
1997; 18:208.
– Hoes AW, Mosterd A, Grobbee DE. An epidemic of heart failure? Recent evidence from
Europe. Eur Heart J 1998; 19 Suppl L:L2.
– Bonneux L, Barendregt JJ, Meeter K, et al. Estimating clinical morbidity due to
ischemic heart disease and congestive heart failure: the future rise of heart failure. Am J
Public Health 1994; 84:20.
– Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013
update: a report from the American Heart Association. Circulation 2013; 127:e6.
– McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart
failure: public and private health burden. Eur Heart J 1998; 19 Suppl P:P9.
– Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic
heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995; 26:1565.
– Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic
ventricular dysfunction in the community: appreciating the scope of the heart failure
epidemic. JAMA 2003; 289:194.
– McDonagh TA, Morrison CE, Lawrence A, et al. Symptomatic and asymptomatic left-
ventricular systolic dysfunction in an urban population. Lancet 1997; 350:829.
– Gardin JM, Siscovick D, Anton-Culver H, et al. Sex, age, and disease affect
echocardiographic left ventricular mass and systolic function in the free-living elderly. The
Cardiovascular Health Study. Circulation 1995; 91:1739.
– Lauer MS, Evans JC, Levy D. Prognostic implications of subclinical left ventricular
dilatation and systolic dysfunction in men free of overt cardiovascular disease (the
Framingham Heart Study). Am J Cardiol 1992; 70:1180.
– Bleumink GS, Knetsch AM, Sturkenboom MC, et al. Quantifying the heart failure
epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The
Rotterdam Study. Eur Heart J 2004; 25:1614.


Medical professionalism is a core element of being a good doctor. Good medical practice is
based on a relationship of trust between the profession and society, in which doctors are
expected to meet the highest standards of professional practice and behavior. It involves a
partnership between patient and doctor that is based on mutual respect, confidentiality,
honesty, responsibility and accountability.

One of the features of responsibility is to ensure the continuity of care. Once a doctor
undertakes the care of patients he should provide continuity of care for the duration of the
illness. If it is decided to withdraw the services, either as an individual practitioner or as
part of a team or group that has decided to withdraw care, it does not release the doctor
from the ethical responsibilities to patients. This means that the doctor must provide
emergency services and any care that may be required by those for whom you hold clinical
responsibility. The doctor should ensure that the safety and welfare of the patients is
protected during his absence. He must ensure that they have appropriate and
comprehensive indemnity insurance or other means for funding in place to cover their care
of patients.

Continuity of Care for Employee

For work related healthcare, doctors have to face intermingling problems of relationship
between employer and the employee. In some countries, there are regulations on work
related disabilities. For example, Americans with Disabilities Act (ADA) imposes a series
of restrictions on an employer's use of medical examinations and inquiries in three
situations: (1) at the application stage; (2) after individuals have been offered a job; and (3)
for existing employees. For existing employee, the ADA prohibits an employer from
requiring "existing employees" to submit to a medical examination or asking an employee
whether he or she has a disability (or the nature or severity of the disability), unless such
examination or inquiry is related to the functions of the employee's job and consistent with
business necessity.

Medical tests are only applied if it is "job-related" and "consistent with business necessity."
For example, if an employer requires a warehouse laborer, whose back impairment affects
his ability to lift, to be examined by an orthopaedist; therefore it is not require the
employee to submit to an HIV test because it is not related to either the essential functions
of his job or to his impairment.

The certification only needs to be a simple statement of the employee's ability to return to
work. For purposes of clarification of the employee's fitness to return to work, a health care
provider employed by the employer may contact the employee's health care provider with
the employee's permission.

Continuity of Care after Cardiac Rehabilitation (CR)

Substantial health risks continue following coronary events and procedures and cardiac
rehabilitation improves subsequent prognosis. However, most research demonstrates low
enrolment and inequality in access to CR. While the literature copiously presents patient
factors related to low utilization, there are also health system and doctor factors at play. For
instance, because of the increasing use of day revascularization surgery, shorter hospital
stays, and frequent movement of cardiac patients from one system of care to another, the
continuity between hospital care and CR programs can be disjointed. There is a lack of
concentration on post-CR care.

Access to CR can be hindered by many factors including distance and transportation

barriers, inconvenient program hours for participants who work during the day, and in the
case of rural or remote patients, lack of a doctor to make the referral. To reach a wider
range of patients and potentially reduce costs, down-referral should be developed to
increase the extent of medical service delivery. Managing continuity of cardiac care
involves the processes of referral to and discharge from cardiac specialist/hospital. Primary
health care providers may benefit from constructive discharge summaries regarding care
provided during CR to ensure appropriate long-term follow-up.

Comhairle na nDochtuiri Leingis Medical Council. (2009): Guide To Professional Conduct
And Ethics For Registered Medical Practitioners, 7th ed. Comhairle na nDochtuiri Leingis
Medical Council, Dublin. pp. 15.
DL Riley, S Krepostman, DE Stewart, N Suskin, HM Arthur, SL Grace. (2009): A mixed
methods study of continuity of care from cardiac rehabilitation to primary care physicians.
Can J Cardiol, 25(6):e187-e192.

Tutor Guide PHOP

Level of Disease Prevention (review)
Primary prevention seeks to prevent the onset of specific diseases via risk reduction: by
altering behaviours or exposures that can lead to disease, or by enhancing resistance to the
effects of exposure to a disease agent. Primary prevention generally targets specific causes
and risk factors for specific diseases, but may also aim to promote healthy behaviours,
improve host resistance, and foster safe environments that reduce the risk of disease, for
instance, thorough cleaning of operating rooms to prevent post-operative infection.

Secondary prevention is preventing the establishment or progression of a disease once a

person has been exposed to it. Examples include early detection via screening procedures
that detect disease at an early stage when intervention may be more cost-effective.

Once a disease has developed and has been treated in its acute clinical phase, tertiary
prevention seeks to soften the impact caused by the disease on the patient’s function,
longevity, and quality of life. Examples include cardiac rehabilitation following a
myocardial infarction, seeking to alter behaviours to reduce the likelihood of a reinfaction.
Tertiary prevention can include modifying risk factors, such as assisting a cardiac patient to
lose weight, or making environmental modifications to reduce an asthmatic patient’s
exposure to allergens.

After review this, let the students to explore themselves what’s the primary and secondary
(or even tertiary) prevention for this cases (based on the case given)

Lifestyle Changes for Heart Failure

Following recommendations about diet, exercise and other habits can help to alleviate
symptoms, slow the disease's progression and improve everyday life. In fact, people with
mild to moderate heart failure often can lead nearly normal lives as a result.
a. Quitting smoking
Each puff of nicotine from tobacco smoke temporarily increases heart rate and blood
pressure, even as less oxygen-rich blood circulates through the body. Smoking also leads to
clumping or stickiness in the blood vessels feeding the heart. People who quit smoking are
more likely to have their heart failure symptoms improve.
b. Losing or maintaining weight
Sudden weight gain or weight loss can be a sign that the patient may be developing heart
failure or that the heart failure is progressing. Weigh at the same time each morning,
preferably before breakfast and after urinating.
c. Tracking daily fluid intake
When body is retaining fluid, as often happens with heart failure, doctor may recommend
limiting how much liquid the patient get. Many people are prescribed diuretics (water pills)
to help them get rid of extra water and sodium and reduce their heart's workload.
d. Avoid Alcohol
e. Avoid or limiting caffeine
Consume only a moderate amount of caffeine per day, no more than a cup or two of coffee.
f. Eating a heart-healthy diet
Eat a healthy diet that's low in saturated fat, trans fat, cholesterol and sodium.

AHA Recommendation:
As part of a healthy diet, an adult consuming 2,000 calories daily should aim for:
Fruits and vegetables: At least 4.5 cups a day
Fish (preferably oily fish): At least two 3.5-ounce servings a week
Fiber-rich whole grains: At least three 1-ounce-equivalent servings a day
Sodium: Less than 1,500 mg a day
Sugar-sweetened beverages: No more than 450 calories (36 ounces) a week
Other Dietary Measures:
Nuts, legumes and seeds: At least 4 servings a week
Processed meats: No more than 2 servings a week
Saturated fat: Less than 7% of total energy intake
g. Being physically active
Avoid sedentary life and do exercise regularly, 2-3 times a week, 30 – 60 minutes each. Do
the aerobic type of exercise such as walking, cycling, and jogging.
h. Managing Stress
Take 15 to 20 minutes a day to sit quietly, breathe deeply and think of a peaceful scene.
Count to 10 before responding when feeling angry to help reduce stress.
i. Keeping track
Keeping track of symptoms and reporting any changes to healthcare professional
j. Monitoring Blood Pressure
k. Getting adequate rest
To improve your sleep at night, use pillows to prop up your head. Avoid naps and big
meals right before bedtime. Try napping after lunch or putting your feet up for a few
minutes every couple of hours.